Ventricular pre-excitation in cats: 17 cases.

OBJECTIVES: Atrioventricular accessory pathways are abnormal electrical connections between the atria and ventricles that predispose to ventricular pre-excitation (VPE) and tachycardias. ANIMALS: Seventeen cats with VPE and 15 healthy matched-control cats. MATERIAL AND METHODS: Multicenter case-control retrospective study. Clinical records were searched for cats with VPE, defined as preserved atrioventricular synchrony, reduced PQ interval, and increased QRS complex duration with a delta wave. Clinical, electrocardiography, echocardiographic, and outcome data were collated. RESULTS: Most cats with VPE were male (16/17 cats), non-pedigree cats (11/17 cats). Median age and mean body weight were 5.4 years (0.3-11.9 years) and 4.6 ± 0.8 kg, respectively. Clinical signs at presentation included lethargy (10/17 cats), tachypnea (6/17 cats), and/or syncope (3/17 cats). In two cats, VPE was an incidental finding. Congestive heart failure was uncommon (3/17 cats). Nine (9/17) cats had tachyarrhythmias: 7/9 cats had narrow QRS complex tachycardia and 2/9 cats had wide QRS complex tachycardia. Four cats had ventricular arrhythmias. Cats with VPE had larger left (P < 0.001) and right (P < 0.001) atria and thicker interventricular septum (P = 0.019) and left ventricular free wall (P = 0.028) than controls. Three cats had hypertrophic cardiomyopathy. Treatment included different combinations of sotalol (5/17 cats), diltiazem (5/17 cats), atenolol (4/17 cats), furosemide (4/17 cats), and platelet inhibitors (4/17 cats). Five cats died, all from cardiac death (median survival time 1882 days [2-1882 days]). CONCLUSIONS: Cats with VPE had a relatively long survival, albeit showing larger atria and thicker left ventricular walls than healthy cats.

Long-term palliation of right-sided congestive heart failure after stenting a recurrent cor triatriatum dexter in a 10½-year-old pug.

A 10½-year-old, male neutered, pug presented with increasing ascites over two months. Echocardiography revealed cor triatriatum dexter with no concurrent cardiovascular anomalies, subsequently confirmed by computed tomography angiography. Balloon dilation of the perforated intra-atrial membrane under fluoroscopic guidance resulted in the transient resolution of all clinical abnormalities, but six months later stenosis and ascites recurred. After repeated balloon dilation, a stent was placed across the membrane. The dog remains asymptomatic fourteen months after the second procedure. One noteworthy feature of this case is the onset of congestive heart failure due to a congenital defect only at more than 10 years of age.

[Atrial dissociation in a boxer with a carcinoma of the middle ear]. / Atriale Dissoziation bei einem Boxer mit Mittelohrkarzinom.

INTRODUCTION: The case report describes an atrial dissociation in a 9-year-old male boxer diagnosed by ECG and echocardiography. Torticollis, severe neck pain and auscultatory arrhythmia were found during the clinical examination. In addition, a mass was found in the left tympanic bulla and histologically a carcinoma of the middle ear was diagnosed.

INTRODUCTION: La présente étude de cas décrit une dissociation auriculaire chez un boxer mâle de 9 ans diagnostiquée par ECG et échocardiographie. Lors de l'examen clinique on a relevé un port de tête penché, des douleurs cervicales sévères et une arythmie à l'auscultation. De plus, une masse a été trouvée dans la bulle tympanique gauche et un carcinome de l'oreille moyenne a été diagnostiqué histologiquement.

Cardiac phenotype in propionic acidemia - Results of an observational monocentric study.

BACKGROUND: Propionic acidemia (PA) is an organic aciduria caused by inherited deficiency of propionyl-CoA carboxylase. Left ventricular dysfunction and QT prolongation may lead to life-threatening complications. Systematic analyses of cardiac phenotypes, in particular effects of specific cardiac therapies, are scarce. METHODS: In this longitudinal observational monocentric study (data from 1989 to 2017) all PA patients treated at our center were included. Echocardiographic parameters (left ventricular end-diastolic diameter: LVEDD, left ventricular shortening fraction, mitral valve Doppler inflow pattern) and 12­lead electrocardiogram recordings (corrected QT interval: QTc) were analyzed. Symptomatic patients were dichotomized to the group "early-onset" (symptoms within 28 days of life) and "late-onset" (symptoms after 28 days). Associations between cardiac function, LVEDD, QTc and clinical parameters (age at onset, beta-blocker or Angiotensin-converting enzyme inhibitor = ACE-I therapy) were analyzed. RESULTS: 18 patients with PA were enrolled, 17 of them were symptomatic and one asymptomatic, with a median age at diagnosis of 6 days. 14/17 (82%) had early onset disease manifestation. Systolic left ventricular dysfunction (i.e. hypokinetic phenotype of cardiomyopathy) was diagnosed in 7/18 (39%) patients at a median age of 14.4 years, all had early onset. Two patients had a dilated left ventricle and systolic left ventricular dysfunction (i.e. dilated hypokinetic phenotype - dilated cardiomyopathy). Diastolic left ventricular dysfunction was found in 11/18 (61%) individuals, typically preceding systolic left ventricular dysfunction. ACE-I therapy did not improve systolic left ventricular function. Mean QTc was 445 ms (+/- 18.11 ms). Longer QTc was associated with larger LVEDD. CONCLUSIONS: Systolic left ventricular dysfunction was found in 39% of patients, reflecting high disease severity. Two thirds of all individuals showed signs of diastolic left ventricular dysfunction usually preceding systolic left ventricular dysfunction; it therefore may be considered as an indicator for early cardiac disease manifestation, possibly allowing earlier treatment modification. Unresponsiveness to routine cardiac therapy highlights the need to evaluate further strategies, such as liver transplantation.

Establishing reference standards for the vasovagal tonus index in a cohort of healthy French Bulldogs.

INTRODUCTION: The vasovagal tonus index (VVTI), a time-domain indicator of heart rate variability, has been suggested as a diagnostic and prognostic tool in dogs with cardiac disease and heart failure. Brachycephalic breeds tend to have a higher VVTI than non-brachycephalic breeds.11 The objective of this study was to obtain standard VVTI reference values from a representative cohort of healthy French Bulldogs based on a single ECG recording. A second aim of this study was to evaluate the practicability of a VVTI screening in the clinical routine by evaluating repeatability of the VVTI across five successive measurements. In order to determine baseline factors potentially influencing the VVTI, the impact of stress, activity and character as well as sex and neutering status were evaluated. Out of 73 French Bulldogs screened, 60 dogs were considered healthy based on their medical history, physical examination, blood pressure and ECG, and no evidence of congenital or acquired heart disease on echocardiographic examination. The VVTI was calculated based on the variance of 20 R-R intervals and the corresponding HR extrapolated to one minute from the same 20 R-R intervals. In addition, a maximum of five consecutive VVTI values were calculated based on 100 successive R-R intervals recorded from each dog. VVTI values ranged from 5.66 to 11.3 with a mean (standard deviation [SD]) of 8.82 (1.43); the corresponding HR ranged from 78 to 173 bpm with a mean (SD) of 120 (23) bpm. Importantly, VVTI and HR values were negatively correlated (R = 0.689; adjusted R² = 0.466), which must be considered for clinical interpretation of the VVTI. The repeatability across five successive sets of 20 heartbeats was shown (mean intra-individual variability of 6.1%). Stress significantly influenced the VVTI and HR (p < 0.001). The VVTI range established in this study may be used as reference to assess the HRV of presumably healthy brachycephalic dogs at routine health checks. Deviations from the reference may permit the clinician to adapt the schedule and focus of subsequent follow-up investigations.

INTRODUCTION: L'indice de tonicité vaso-vagal (VVTI) est un indicateur temporel de la variabilité de la fréquence cardiaque; il est décrit comme un outil de diagnostic et de pronostic chez les chiens atteints de maladie cardiaque et d'insuffisance cardiaque. Les races brachycéphales ont tendance à avoir un VVTI plus élevé que les races non brachycéphales.11 Le but de cette étude était de déterminer les valeurs de référence VVTI à partir d'une cohorte représentative de bouledogues français en bonne santé à l'aide d'un enregistrement ECG. Un deuxième objectif de cette étude était d'évaluer la faisabilité du dépistage du VVTI dans la pratique clinique quotidienne en examinant la répétabilité du VVTI sur cinq mesures consécutives. Afin de déterminer les facteurs de base susceptibles d'affecter le VVTI, les effets du stress, de l'activité et du caractère, ainsi que le sexe et le statut de castration ont été évalués. Sur les 73 bouledogues français examinés, 60 chiens ont été jugés en bonne santé sur la base de leurs antécédents médicaux, de leur examen médical, de leur tension artérielle et de leur électrocardiogramme et aucun examen échocardiographique n'a révélé de maladie cardiaque congénitale ou acquise. Le VVTI a été calculé sur la variance de 20 intervalles R-R et sur la fréquence cardiaque extrapolée (HR) correspondante. De plus, un maximum de cinq valeurs VVTI consécutives ont été calculées pour chaque chien sur la base de 100 intervalles R-R consécutifs. Les valeurs de VVTI allaient de 5,66 à 11,3 avec une moyenne (écart type [SD] de 8,82 (1,43). La fréquence cardiaque correspondante était comprise entre 78 et 173 battements par minute avec une moyenne (SD) de 120 (23) battements par minute. Pour l'interprétation clinique de VVTI, la corrélation négative entre VVTI et HR (R = 0,689; R2 ajusté = 0,466) doit être prise en compte. La répétabilité a été vérifiée sur cinq séries consécutives de 20 pulsations (variabilité intra-sujet moyenne de 6,1%). Le stress a affecté de manière significative le VVTI et la HR (p.

[Primary histiocytic sarcoma of the aortic valve as a trigger of heart failure in a crossbreed dog]. / Primäres histiozytäres Sarkom der Aortenklappe als Auslöser von Herz­versagen bei einem Mischlingshund.

INTRODUCTION: A case of a histiocytic sarcoma at the aortic valve with multiple metastases in the ventricular myocardium, ventricular endocardium and mitral valves in a male crossbreed dog is described. Neoplasia resulted in intermittent forward heart failure, thrombosis, myocardial infarction, and ventricular tachycardia.

INTRODUCTION: On décrit le cas, chez un chien croisé, d'un sarcome histiocytaire de la valvule aortique avec de multiples métastases dans le myocarde ventriculaire, l'endocarde ventriculaire et la valvule mitrale. Le néoplasie conduisait à une faiblesse, à des thromboses et des infarctus du myocarde ainsi qu'à une tachycardie ventriculaire.

Fetal hemodynamic response to aortic valvuloplasty and postnatal outcome: a European multicenter study.

OBJECTIVE: Fetal aortic stenosis may progress to hypoplastic left heart syndrome. Fetal valvuloplasty (FV) has been proposed to improve left heart hemodynamics and maintain biventricular (BV) circulation. The aim of this study was to assess FV efficacy by comparing survival and postnatal circulation between fetuses that underwent FV and those that did not. METHODS: This was a retrospective multicenter study of fetuses with aortic stenosis that underwent FV between 2005 and 2012, compared with contemporaneously enrolled natural history (NH) cases sharing similar characteristics at presentation but not undergoing FV. Main outcome measures were overall survival, BV-circulation survival and survival after birth. Secondary outcomes were hemodynamic change and left heart growth. A propensity score model was created including 54/67 FV and 60/147 NH fetuses. Analyses were performed using logistic, Cox or linear regression models with inverse probability of treatment weighting (IPTW) restricted to fetuses with a propensity score of 0.14-0.9, to create a final cohort for analysis of 42 FV and 29 NH cases. RESULTS: FV was technically successful in 59/67 fetuses at a median age of 26 (21-34) weeks. There were 7/72 (10%) procedure-related losses, and 22/53 (42%) FV babies were delivered at < 37 weeks. IPTW demonstrated improved survival of liveborn infants following FV (hazard ratio, 0.38; 95% CI, 0.23-0.64; P = 0.0001), after adjusting for circulation and postnatal surgical center. Similar proportions had BV circulation (36% for the FV cohort and 38% for the NH cohort) and survival was similar between final circulations. Successful FV cases showed improved hemodynamic response and less deterioration of left heart growth compared with NH cases (P ≤ 0.01). CONCLUSIONS: We report improvements in fetal hemodynamics and preservation of left heart growth following successful FV compared with NH. While the proportion of those achieving a BV circulation outcome was similar in both cohorts, FV survivors showed improved survival independent of final circulation to 10 years' follow-up. However, FV is associated with a 10% procedure-related loss and increased prematurity compared with the NH cohort, and therefore the risk-to-benefit ratio remains uncertain. We recommend a carefully designed trial incorporating appropriate and integrated fetal and postnatal management strategies to account for center-specific practices, so that the benefits achieved by fetal therapy vs surgical strategy can be demonstrated clearly. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Targeting dendritic cells for the treatment of autoimmune disorders.

In the last decades, it has been recognized that extracellular vesicles (EVs) are not only cell debris with no biological role, but instead they play a key role in information exchange between cells either in health and disease conditions. EVs exhibit indeed their biological role in a pleiotropic manner. They can modulate immune responses through the activation, transfer or removal of surface receptors on target cells, the removal of cytolytic components such as membrane attack complexes, and the transfer of signaling molecules/effectors, such as nucleic acid species, infectious particles, and oncogenes. Among the naturally-derived nanoparticles that have been developed in the last years, stimuli responsive exosomes drew special attention since they intrinsically possess many attributes of a desirable drug delivery system. Their small size allows them to bypass the mononuclear phagocytic system (MPS) clearance, thereby prolonging their circulation time for passive targeting to inflammatory tissues. Moreover, they can deliver their cargo directly into the cytosol, avoiding the lysosomal/endosomal pathway and thus, increasing the transfection efficiency when they are used as gene delivery systems. of This review offers the state of the art knowledge on the physiology and properties of EVs, namely, apoptotic vesicles, microvesicles and exosomes as innovative drug delivery systems for gene therapy, with a special focus on targeting dendritic cells for the treatment of autoimmune disorders.

Evidence of cardiac injury and arrhythmias in dogs with acute kidney injury.

OBJECTIVES: Cardiac involvement in the course of acute kidney injury is described in humans as cardiorenal syndrome type 3 but has received only limited attention in dogs. This study was designed to evaluate cardiac injury and dysfunction in acute kidney injury in dogs and its association with outcome. METHODS: This prospective cohort study enrolled 24 client-owned dogs with acute kidney injury. Cardiac disorders were evaluated with thoracic radiographs, echocardiography, 24-hour Holter monitoring and cardiac troponin I concentrations within 2 days of admission and 7 to 10 days later. RESULTS: Most dogs were diagnosed with leptospirosis (n=18, 75%) and presented with moderate-to-severe acute kidney injury, International Renal Interest Society grades III to V. Dogs with ê100 ventricular premature complexes per 24 hour in the first examination (n=8) had significantly higher initial cTnI concentrations (P=0·007) compared to dogs with fewer than 100. In receiver operating characteristic curve analysis, the number of ventricular premature complexes was predictive of outcome (AUC 0·83, P<0·001). CLINICAL SIGNIFICANCE: Acute kidney injury seems to be associated with cardiac injury and arrhythmias in dogs. The data do not indicate a cardiac cause of poor outcome in dogs with increased number of ventricular premature complexes but the association may reflect the severity of disease.

Natural history of 107 cases of fetal aortic stenosis from a European multicenter retrospective study.

OBJECTIVES: Fetal aortic valvuloplasty (FV) aims to prevent fetal aortic valve stenosis progressing into hypoplastic left heart syndrome (HLHS), which results in postnatal univentricular (UV) circulation. Despite increasing numbers of FVs performed worldwide, the natural history of the disease in fetal life remains poorly defined. The primary aim of this study was to describe the natural history of fetal aortic stenosis, and a secondary aim was to test previously published criteria designed to identify cases of emerging HLHS with the potential for a biventricular (BV) outcome after FV. METHODS: From a European multicenter retrospective study of 214 fetuses with aortic stenosis (2005-2012), 107 fetuses in ongoing pregnancies that did not undergo FV were included in this study and their natural history was reported. We examined longitudinal changes in Z-scores of aortic and mitral valve and left ventricular dimensions and documented direction of flow across the foramen ovale and aortic arch, and mitral valve inflow pattern and any gestational changes. Data were used to identify fetuses satisfying the Boston criteria for emerging HLHS and estimate the proportion of these that would have been ideal FV candidates. We applied the threshold score whereby a score of 1 was assigned to fetuses for each Z-score meeting the following criteria: left ventricular length and width > 0; mitral valve diameter > -2; aortic valve diameter > -3.5; and pressure gradient across either the mitral or aortic valve > 20 mmHg. We compared the predicted circulation with known survival and final postnatal circulation (BV, UV or conversion from BV to UV). RESULTS: Among the 107 ongoing pregnancies there were eight spontaneous fetal deaths and 99 livebirths. Five were lost to follow-up, five had comfort care and four had mild aortic stenosis not requiring intervention. There was intention-to-treat in these 85 newborns but five died prior to surgery, before circulation could be determined, and thus 80 underwent postnatal procedures with 44 BV, 29 UV and seven BV-to-UV circulatory outcomes. Of newborns with intention-to-treat, 69/85 (81%) survived ≥ 30 days. Survival at median 6 years was superior in cases with BV circulation (P = 0.041). Those with a postnatal UV circulation showed a trend towards smaller aortic valve diameters at first scan than did the BV cohort (P = 0.076), but aortic valve growth velocities were similar in both cohorts to term. In contrast, the mitral valve diameter was significantly smaller at first scan in those with postnatal UV outcomes (P = 0.004) and its growth velocity (P = 0.008), in common with the left ventricular inlet length (P = 0.004) and width (P = 0.002), were reduced significantly by term in fetuses with UV compared with BV outcome. Fetal data, recorded before 30 completed gestational weeks, from 70 treated neonates were evaluated to identify emerging HLHS. Forty-four had moderate or severe left ventricular depression and 38 of these had retrograde flow in the aortic arch and two had left-to-right flow at atrial level and reversed a-waves in the pulmonary veins. Thus 40 neonates met the criteria for emerging HLHS and BV circulation was documented in 13 (33%). Of these 40 cases, 12 (30%) had a threshold score of 4 or 5, of which five (42%) had BV circulation without fetal intervention. CONCLUSIONS: The natural history in our cohort of fetuses with aortic stenosis and known outcomes shows that a substantial proportion of fetuses meeting the criteria for emerging HLHS, with or without favorable selection criteria for FV, had a sustained BV circulation without fetal intervention. This indicates that further work is needed to refine the selection criteria to offer appropriate therapy to fetuses with aortic stenosis. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Fetal aortic valvuloplasty: investigating institutional bias in surgical decision-making.

OBJECTIVES: Fetal aortic valvuloplasty may prevent the progression of aortic stenosis to hypoplastic left heart syndrome and allow biventricular rather than univentricular postnatal treatment. This study aimed to investigate whether blinded simulation of a multidisciplinary team approach aids interpretation of multicenter data to uncover institutional bias in postnatal decision-making following fetal cardiac intervention for aortic stenosis. METHODS: The study included 109 cases of prenatally diagnosed aortic stenosis from 13 European countries, of which 32 had undergone fetal cardiac intervention. The multidisciplinary team, blinded to fetal cardiac intervention, institutional location and postnatal treatment, retrospectively assigned a surgical pathway (biventricular or univentricular) based on a review of recorded postnatal imaging and clinical characteristics. The team's decisions were the numerical consensus of silent voting, with case review when a decision was split. Funnel plots showing concordance between the multidisciplinary team and the local team's surgical choice (first pathway) and with outcome (final pathway) were created. RESULTS: In 105 cases the multidisciplinary team reached a consensus decision regarding the surgical pathway, with no decision in four cases because the available imaging records were inadequate. Blinded multidisciplinary team consensus for the first pathway matched the decision of the surgical center in 93/105 (89%) cases, with no difference in agreement between those that had undergone successful fetal cardiac intervention (n = 32) and no (n = 74) or unsuccessful (n = 3) valvuloplasty (no fetal cardiac intervention) (κ = 0.73 (95% CI, 0.38-1.00) vs 0.74 (95% CI, 0.51-0.96)). However, funnel plots comparing multidisciplinary team individual decisions with those of the local teams displayed more discordance (meaning biventricular-univentricular conversion) for the final surgical pathway following fetal cardiac intervention than they did for cases without such intervention (36/74 vs 34/130; P = 0.002), and identified one outlying center. CONCLUSIONS: The use of a blinded multidisciplinary team to simulate decision-making and presentation of data in funnel plots may assist in the interpretation of data submitted to multicenter studies and permit the identification of outliers for further investigation. In the case of aortic stenosis, a high level of agreement was observed between the multidisciplinary team and the surgical centers, but one outlying center was identified.

Expression of serum amyloid A4 in human trophoblast-like choriocarcinoma cell lines and human first trimester/term trophoblast cells.

Trophoblast invasion into uterine tissues represents a hallmark of first trimester placental development. As expression of serum amyloid A4 (SAA4) occurs in tumorigenic and invasive tissues we here investigated whether SAA4 is present in trophoblast-like human AC1-M59/Jeg-3 cells and trophoblast preparations of human first trimester and term placenta. SAA4 mRNA was expressed in non-stimulated and cytokine-treated AC1-M59/Jeg-3 cells. In purified trophoblast cells SAA4 mRNA expression was upregulated at weeks 10 and 12 of pregnancy. Western-blot and immunohistochemical staining of first trimester placental tissue revealed pronounced SAA4 expression in invasive trophoblast cells indicating a potential role of SAA4 during invasion.

Longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables in dogs with myxomatous mitral valve disease receiving pimobendan or benazepril: the QUEST study.

BACKGROUND: Myxomatous mitral valve disease (MMVD) is an important cause of morbidity and mortality in dogs. OBJECTIVES: To compare, throughout the period of follow-up of dogs that had not yet reached the primary endpoint, the longitudinal effects of pimobendan versus benazepril hydrochloride treatment on quality-of-life (QoL) variables, concomitant congestive heart failure (CHF) treatment, and other outcome variables in dogs suffering from CHF secondary to MMVD. ANIMALS: A total of 260 dogs in CHF because of MMVD. METHODS: A prospective single-blinded study with dogs randomized to receive pimobendan (0.4-0.6 mg/kg/day) or benazepril hydrochloride (0.25-1.0 mg/kg/day). Differences in outcome variables and time to intensification of CHF treatment were compared. RESULTS: A total of 124 dogs were randomized to pimobendan and 128 to benazepril. No difference was found between groups in QoL variables during the trial. Time from inclusion to 1st intensification of CHF treatment was longer in the pimobendan group (pimobendan 98 days, IQR 30-276 days versus benazepril 59 days, IQR 11-121 days; P = .0005). Postinclusion, dogs in the pimobendan group had smaller heart size based on VHS score (P = .013) and left ventricular diastolic (P = .035) and systolic (P = .0044) dimensions, higher body temperature (P = .030), serum sodium (P = .0027), and total protein (P = .0003) concentrations, and packed cell volume (P = .030). Incidence of arrhythmias was similar in treatment groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan versus benazepril resulted in similar QoL during the study, but conferred increased time before intensification of CHF treatment. Pimobendan treatment resulted in smaller heart size, higher body temperature, and less retention of free water.

[Atrial rupture and pericardial effusion as a complication of chronic mitral valve endocardiosis]. / Komplikation der chronischen Mitralendokardiose: Vorhofruptur und Herzbeutelerguss.

A 9-year-old Labrador mixed breed dog, known to suffer from heart disease, was presented. It had recently collapsed on the street. Based on clinical findings and ultrasonography the tentative diagnosis of an atrial rupture with bleeding into the pericardial sac, resulting into a cardiac tamponade, was made. The dog's state of health improved under treatment, including infusion, sedation and analgesia. Therefore pericardiocentesis was unnecessary. The dog was released from hospital the next evening and the medical therapy of its heart disease was continued. The animal died 85 days later.

Polyhydroxy surfactants for the formulation of lipid nanoparticles (SLN and NLC): effects on size, physical stability and particle matrix structure.

The two polyhydroxy surfactants polyglycerol 6-distearate (Plurol(®)Stearique WL1009 - (PS)) and caprylyl/capryl glucoside (Plantacare(®) 810 - (PL)) are a class of PEG-free stabilizers, made from renewable resources. They were investigated for stabilization of aqueous solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) dispersions. Production was performed by high pressure homogenization, analysis by photon correlation spectroscopy (PCS), laser diffraction (LD), zeta potential measurements and differential scanning calorimetry (DSC). Particles were made from Cutina CP as solid lipid only (SLN) and its blends with Miglyol 812 (NLC, the blends containing increasing amounts of oil from 20% to 60%). The obtained particle sizes were identical for both surfactants, about 200 nm with polydispersity indices below 0.20 (PCS), and unimodal size distribution (LD). All dispersions with both surfactants were physically stable for 3 months at room temperature, but Plantacare (PL) showing a superior stability. The melting behaviour and crystallinity of bulk lipids/lipid blends were compared to the nanoparticles. Both were lower for the nanoparticles. The crystallinity of dispersions stabilized with PS was higher, the zeta potential decreased with storage time associated with this higher crystallinity, and leading to a few, but negligible larger particles. The lower crystallinity particles stabilized with PL remained unchanged in zeta potential (about -50 mV) and in size. These data show that surfactants have a distinct influence on the particle matrix structure (and related stability and drug loading), to which too little attention was given by now. Despite being from the same surfactant class, the differences on the structure are pronounced. They are attributed to the hydrophobic-lipophilic tail structure with one-point anchoring in the interface (PL), and the loop conformation of PS with two hydrophobic anchor points, i.e. their molecular structure and its interaction with the matrix surface and matrix bulk. Analysis of the effects of the surfactants on the particle matrix structure could potentially be used to further optimization of stability, drug loading and may be drug release.

Two further cases supporting nonsurgical management in congenital lobar emphysema.

BACKGROUND: For decades, the well-established standard recommended treatment for patients with congenital lobar emphysema (CLE) and respiratory distress has been lobectomy of the affected lobe or lobes, whereas indications for conservative management have been controversially discussed. PATIENTS/METHODS: Description of the clinical courses including the results of diagnostic procedures and the resulting therapeutic strategies in 2 patients with congenital lobar emphysema. We review the literature on conservatively treated patients with congenital lobar emphysema. RESULTS: Considering that formerly asserted hypotheses postulating benefits of surgical treatment cannot unambiguously be corroborated from cases in literature, we could show that conservative treatment in patients with congenital lobar emphysema is appropriate in mildly to moderately symptomatic children. CONCLUSION: Conservative treatment of children with congenital lobar emphysema is an attractive option, whenever justifiable on medical grounds. Our cases may serve as paradigms in decision-making processes in similar cases and - together with the literature review - may be helpful to avoid unnecessary lobectomies in children. Patients treated conservatively will need a close follow-up, and further data on long-term follow-up courses are desirable.

Serum amyloid A: an acute-phase protein involved in tumour pathogenesis.

The synthesis of acute-phase protein serum amyloid A (SAA) is largely regulated by inflammation- associated cytokines and a high concentration of circulating SAA may represent an ideal marker for acute and chronic inflammatory diseases. However, SAA is also synthesized in extrahepatic tissues, e.g. human carcinoma metastases and cancer cell lines. An increasing body of in vitro data supports the concept of involvement of SAA in carcinogenesis and neoplastic diseases. Accumulating evidence suggests that SAA might be included in a group of biomarkers to detect a pattern of physiological events that reflect the growth of malignancy and host response. This review is meant to provide a broad overview of the many ways that SAA could contribute to tumour development, and accelerate tumour progression and metastasis, and to gain a better understanding of this acute-phase reactant as a possible link between chronic inflammation and neoplasia.

A novel element in the management of chronic granulomatous disease (CGD)? - treatment of osteomyelitis with additional hyperbaric oxygen therapy (HBO).

Chronic granulomatous disease (CGD) is caused by malfunctioning of the phagocyte NADPH oxidase responsible for the generation of microbicidal reactive oxygen species. It is characterized by severe recurrent infections with catalase positive bacteria. Bacterial or fungal osteomyelitis is a common complication which often does not respond sufficiently to intravenous antibiotic treatment. We report the case of a four year old boy with CGD and osteomyelitis of the mandible refractory to intravenous antibiotic therapy. Introduction of hyperbaric oxygen therapy (HBO) was well tolerated and led to resolution of the osteomyelitis.