Measurement of an Excess in the Yield of J/ψ at Very Low p_{T} in Pb-Pb Collisions at sqrt[s]_{NN}=2.76 TeV.

We report on the first measurement of an excess in the yield of J/ψ at very low transverse momentum (p_{T}<0.3 GeV/c) in peripheral hadronic Pb-Pb collisions at sqrt[s_{NN}]=2.76 TeV, performed by ALICE at the CERN LHC. Remarkably, the measured nuclear modification factor of J/ψ in the rapidity range 2.5

Centrality Dependence of the Charged-Particle Multiplicity Density at Midrapidity in Pb-Pb Collisions at sqrt[s_{NN}]=5.02 TeV.

The pseudorapidity density of charged particles, dN_{ch}/dη, at midrapidity in Pb-Pb collisions has been measured at a center-of-mass energy per nucleon pair of sqrt[s_{NN}]=5.02 TeV. For the 5% most central collisions, we measure a value of 1943±54. The rise in dN_{ch}/dη as a function of sqrt[s_{NN}] is steeper than that observed in proton-proton collisions and follows the trend established by measurements at lower energy. The increase of dN_{ch}/dη as a function of the average number of participant nucleons, ⟨N_{part}⟩, calculated in a Glauber model, is compared with the previous measurement at sqrt[s_{NN}]=2.76 TeV. A constant factor of about 1.2 describes the increase in dN_{ch}/dη from sqrt[s_{NN}]=2.76 to 5.02 TeV for all centrality classes, within the measured range of 0%-80% centrality. The results are also compared to models based on different mechanisms for particle production in nuclear collisions.

Anisotropic Flow of Charged Particles in Pb-Pb Collisions at √[s{NN}]=5.02 TeV.

We report the first results of elliptic (v_{2}), triangular (v_{3}), and quadrangular (v_{4}) flow of charged particles in Pb-Pb collisions at a center-of-mass energy per nucleon pair of sqrt[s_{NN}]=5.02 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurements are performed in the central pseudorapidity region |η|<0.8 and for the transverse momentum range 0.2

Correlated Event-by-Event Fluctuations of Flow Harmonics in Pb-Pb Collisions at sqrt[s_{NN}]=2.76 TeV.

We report the measurements of correlations between event-by-event fluctuations of amplitudes of anisotropic flow harmonics in nucleus-nucleus collisions, obtained for the first time using a new analysis method based on multiparticle cumulants in mixed harmonics. This novel method is robust against systematic biases originating from nonflow effects and by construction any dependence on symmetry planes is eliminated. We demonstrate that correlations of flow harmonics exhibit a better sensitivity to medium properties than the individual flow harmonics. The new measurements are performed in Pb-Pb collisions at the center-of-mass energy per nucleon pair of sqrt[s_{NN}]=2.76 TeV by the ALICE experiment at the Large Hadron Collider. The centrality dependence of correlation between event-by-event fluctuations of the elliptic v_{2} and quadrangular v_{4} flow harmonics, as well as of anticorrelation between v_{2} and triangular v_{3} flow harmonics are presented. The results cover two different regimes of the initial state configurations: geometry dominated (in midcentral collisions) and fluctuation dominated (in the most central collisions). Comparisons are made to predictions from Monte Carlo Glauber, viscous hydrodynamics, ampt, and hijing models. Together with the existing measurements of the individual flow harmonics the presented results provide further constraints on the initial conditions and the transport properties of the system produced in heavy-ion collisions.

Structural activity relationship analysis (SAR) and in vitro testing reveal the anti-ageing potential activity of acetyl aspartic acid.

BACKGROUND: Acetyl aspartic acid (A-A-A) was discovered through gene array analysis with corresponding connectivity mapping (Cmap), aiming for identification of new compounds with anti-ageing properties. OBJECTIVE: The aim of this study was to use structural activity relationship (SAR) analysis to identify a predictive mechanism of action of A-A-A. The findings from SAR will be further characterized by in vitro activity testing. Furthermore, we aimed to investigate the role of polymerized filamentous F-actin in ageing fibroblasts and to evaluate the effect of A-A-A on this model. METHODS: To predict the mode of action of A-A-A, we used the PASS computer program as a SAR model. In vitro, scratch motility tests with immortalized keratinocytes were used as a model for wound healing potential. Matrix metalloproteinase 1-3 (MMP 1-3) was analysed using multiplex protein assays (Luminex), and polymerized actin was detected by phalloidin staining in dermal fibroblasts (HDF). RESULTS: SAR analysis predicted that A-A-A would possess both epidermal and dermal activities with identification of wound healing and MMP inhibition potential. Further in vitro studies confirmed the wound healing potential using keratinocyte scratch motility assays. We were also able to confirm the dermal activities predicted by inhibition of MMP (MMP 1-3) in HDF by A-A-A. In addition, we found a positive relationship between age and F-actin expression. We also discovered that stimulation of HDF with A-A-A for 72 h significantly reduced the polymerized cytoskeletal network as visualized by inhibition of F-actin expression. In fact, A-A-A leveraged the expression of F-actin in middle-aged female fibroblasts (50 years of age) to the level of young female fibroblasts (30 years of age), corresponding to a 40% reduction in F-actin expression. CONCLUSION: Using an in silico and in vitro approach, we were able to demonstrate that A-A-A has the capacity to target different compartments of the skin through keratinocyte regeneration, MMP inhibition and relief in fibroblasts stiffness by reduction of F-actin cytoskeletal network in HDF.

Outbreak of cholera in Tilathi VDC Saptari Nepal.

BACKGROUND: On 2011, Cluster of cholera cases was reported in the Tilathi VDC of Saptari, Nepal. OBJECTIVE: The outbreak was investigated to identify the etiological agent and possible source of infection and guiding the prevention and control measures. METHODS: Demographic and clinical details were collected from the suspected case-patients, and the outbreak was described by time, place, and person. Focus group discussion and Key informant interview were conducted to assess the practice of sanitation, source of drinking water and probable cause of diarrheal disease. Five stool samples and 10 water samples of tube well and ponds were collected and microbiological study was done in BPKIHS Dharan. RESULTS: A total of 111 persons suffered with diarrhea and 02 died of it (attack rate 3.05%, case fatality rate 1.8%). All age groups were affected with disease (median age 26 yrs) and males were affected more than females. Descriptive epidemiology suggested the clustering of cases were around the pond where they clean utensils, take bath and wash clothes. The Vibrio cholerae 01 El Tor, Ogawa serotype was isolated in 03 out of 05 suspected stool samples and in all three of the pond water samples. They reported that most of the houses do not have the toilet and people do not wash their hands regularly with soap and water after defecation. CONCLUSION: Vibrio cholerae was the causative agent behind the outbreak and probable source of infection was the problematic pond water which they used for different purpose. Immediate chlorination of the pond was recommended to halt further spread of the epidemics.

Low yield but high levels of multidrug resistance in urinary tract infections in a tertiary hospital, Nepal.

SETTING: There are concerns about the occurrence of multidrug resistance (MDR) in patients with urine tract infections (UTI) in Nepal. OBJECTIVE: To determine culture positivity, trends in MDR among Escherichia coli and Klebsiella pneumoniae infections and seasonal changes in culture-positive UTI specimens isolated from 2014 to 2018 at the B P Koirala Institute of Health Sciences, Dharan, Eastern Nepal. DESIGN: This was a cross-sectional study using secondary laboratory data. RESULTS: Among 116,417 urine samples tested, 19,671 (16.9%) were culture-positive, with an increasing trend in the number of samples tested and culture positivity. E. coli was the most common bacteria (54.3%), followed by K. pneumoniae (8.8%). Among E. coli and K. pneumoniae isolates, MDR was found in respectively 42.5% and 36.0%. MDR was higher in males and people aged >55 years, but showed a decreasing trend over the years. The numbers of isolates increased over the years, with a peak always observed from July to August. CONCLUSION: Low culture positivity is worrying and requires further work into improving diagnostic protocols. Decreasing trends in MDR are a welcome sign. Information on seasonal changes that peak in July-August can help laboratories better prepare for this time with adequate buffer stocks to ensure culture and antibiotic susceptibility testing.

CONTEXTE: La résistance à plusieurs médicaments (MDR) chez les patients atteints d'infections urinaires (UTI) au Népal est un sujet de préoccupations. OBJECTIF: Déterminer le taux de positivité des cultures, les tendances de MDR parmi les infections à Escherichia coli et Klebsiella pneumoniae et les variations saisonnières dans les échantillons d'UTI positifs par culture de 2014 à 2018 au BP Koirala Institute of Health Sciences, Dharan, Népal oriental. MÉTHODE: Il s'agissait d'une étude transversale réalisée en utilisant des données de laboratoire secondaires. RÉSULTATS: Parmi les 116 417 échantillons urinaires testés, 19 671 (16,9%) étaient positifs par culture, avec une tendance à la hausse du nombre d'échantillons testés et du taux de positivité par culture. E. coli était la bactérie la plus fréquente (54,3%), suivie de K. pneumoniae (8,8%). Une MDR a été observée chez respectivement 42,5% et 36,0% des isolats de E. coli et de K. pneumoniae. La MDR était plus élevée chez les hommes et les personnes âgées >55 ans, mais une tendance à la baisse a été observée au fil des ans. Le nombre d'isolats a augmenté au fil des ans, avec un pic toujours observé de juillet à août. CONCLUSION: Le faible taux de positivité par culture est préoccupant et d'autres études sont nécessaires pour améliorer les protocoles diagnostiques. Les tendances à la baisse en matière de MDR sont un signe encourageant. Les informations relatives aux variations saisonnières avec un pic en juillet-août peuvent aider les laboratoires à mieux se préparer en prévision de cette période, en renouvelant les stocks de solutions tampons afin de pouvoir réaliser les cultures et les tests de sensibilité aux médicaments.

Biological variation of routine haematology and biochemistry measurands in the horse.

BACKGROUND: Clinical pathology results are typically interpreted by referring to population-based reference intervals. The use of individualised (subject-based) reference intervals is more appropriate for measurands with a high degree of variation between individuals. OBJECTIVES: To determine the biological variation of routinely analysed equine haematology and biochemistry measurands and calculate indices of individuality and reference change values which enable production of individualised reference intervals, in a group of healthy, privately owned horses. STUDY DESIGN: In a prospective cohort study, thirty-nine privately owned horses were sampled by jugular venipuncture for analysis of haematology and biochemistry measurands at weekly intervals for 6 weeks. METHODS: Haematology was analysed on the day of collection. Serum was frozen and biochemistry analyses performed on thawed samples. Duplicate results were obtained and the coefficient of variation was calculated for analytical variation, within-subject variation and between-subject variation. The index of individuality and reference change value were derived for each measurand. RESULTS: Haematology (red blood cell count, mean corpuscular haemoglobin and mean cell volume) and biochemistry measurands (total protein, globulins, albumin, gamma-glutamyl transferase, aspartate aminotransferase) demonstrated high individuality, indicating that individualised reference intervals are more appropriate for evaluation of these measurands. Two haematology (mean corpuscular haemoglobin concentration and platelets) and three biochemistry measurands (chloride, glucose and sodium) had low individuality, indicating that the use of traditional population-based reference intervals is appropriate for these measurands. Remaining measurands had intermediate individuality suggesting interpretation of the reference change value should occur with consideration of the population-based reference interval. MAIN LIMITATIONS: The use of privately owned horses, variable management and environmental factors. CONCLUSIONS: The use of individualised reference intervals is justified for many measurands in horses, supporting the use of serial sampling, consideration of biological variation and application of reference change values for improved clinical decision making and patient management in equine practice.

Clinical application of biological variation data to facilitate interpretation of canine and feline laboratory results.

Interpretation of laboratory results is based on comparison of the patient's own results against established decision thresholds or reference intervals in the context of the clinical presentation and history. Blood measurand analysis has pre-analytical, analytical and physiological sources of variation, which may complicate interpretation of results. Biological variation describes the physiological random fluctuation of blood measurands around a homeostatic set point, which varies within and between individuals. This article reviews the practical applications of biological variation in the everyday clinical setting. Examples are offered to highlight how biological variation can be used to: (1) assess the usefulness of subject-based reference intervals, (2) determine measurand homeostatic set points, (3) interpret single or serial results for diagnosis of disease and (4) evaluate changes in serial results during monitoring.

Measurement of azimuthal correlations of D mesons with charged particles in pp collisions at [Formula: see text] TeV and p-Pb collisions at [Formula: see text] TeV.

The azimuthal correlations of D mesons with charged particles were measured with the ALICE apparatus in pp collisions at [Formula: see text] and p-Pb collisions at [Formula: see text] at the Large Hadron Collider. [Formula: see text], [Formula: see text], and [Formula: see text] mesons and their charge conjugates with transverse momentum [Formula: see text] and rapidity in the nucleon-nucleon centre-of-mass system [Formula: see text] (pp collisions) and [Formula: see text] (p-Pb collisions) were correlated to charged particles with [Formula: see text]. The yield of charged particles in the correlation peak induced by the jet containing the D meson and the peak width are compatible within uncertainties in the two collision systems. The data are described within uncertainties by Monte-Carlo simulations based on PYTHIA, POWHEG, and EPOS 3 event generators.

Naturally-occurring chronic renal disease in Australian cats: a prospective study of 184 cases.

OBJECTIVE: To describe cases of naturally occurring feline chronic renal disease (CRD) in a defined population of Sydney. DESIGN: Prospective case series. METHODS: The inclusion criteria were the presence of a serum creatinine concentration above the reference range with either inadequately concentrated urine (urine specific gravity < or = 1.035), necropsy findings consistent with CRD, renal proteinuria or persistent azotaemia despite rehydration. Cats were excluded if a specific aetiology was identified ante or post mortem. Patients were divided into two categories (renal insufficiency or renal failure) on the basis of history, physical findings and serum creatinine concentration. The gender and age of cats with CRD was compared to an estimated Australian urban pet cat population. The breeds of cats with CRD were compared to the breeds of cats visiting the respective veterinary hospital where possible. Breed and gender comparisons were made using Fisher's exact tests. Age comparisons were made using Mann-Whitney U tests. The age at which cats were diagnosed with CRD was compared between veterinary hospitals using a Kruskal-Wallis test. RESULTS: One hundred and eighty-four (99 female; 85 male) cats fulfilled the inclusion criteria. Amongst cats with CRD, males (median 12 years) were significantly younger than females (median 15 years; p = 0.001). The overall proportion of male and female cats with CRD was similar to that of the reference urban cat population (p = 0.41), however, between the ages of 9 and 11 years, male cats with CRD were over-represented (p = 0.038). Patients diagnosed with renal insufficiency (123 cats; median age 15 years) were significantly older than patients diagnosed with renal failure (61 cats; median age 11 years; p = 0.0001). The age at diagnosis of cats with CRD differed significantly between veterinary hospitals (p = 0.002). CONCLUSION: Male cats with CRD were significantly younger than female cats with CRD. Younger cats were more likely to be diagnosed at an advanced stage of disease than older cats. The age at which cats were diagnosed with CRD was influenced by the clinic the cats attended. Whether these differences reflect differences in the aetiology of CRD or in the rate of disease progression warrants further investigation. Breed did not appear to play a significant role in the development of CRD in this survey.

Susceptibility of bacteria from feline and canine urinary tract infections to doxycycline and tetracycline concentrations attained in urine four hours after oral dosage.

OBJECTIVES: To measure urinary concentrations of doxycycline in cats and dogs and tetracycline in dogs 4 h after conventional oral dosing and determine whether these antibiotics were present in sufficient concentrations to be effective against common feline and canine urinary tract pathogens as assessed in vitro by Epsilometer and disc diffusion antimicrobial susceptibility methods. DESIGN: A prospective study involving oral administration to clinically normal cats and dogs of doxycycline or tetracycline (dogs only) and culture of bacteria from dogs and cats with urinary tract infections to determine their susceptibility to both doxycycline and tetracycline in vitro. PROCEDURE: In the first study, nine cats and eight dogs were administered doxycycline monohydrate (5 mg/kg every 12 h) and a further eight dogs were administered tetracycline hydrochloride (20 mg/kg every 8 h) for 72 h. Blood was collected at 2 and 4 h, and urine at 4 h, after the last dose. The concentration of each agent in serum and urine was determined by modified agar diffusion. In the second study, 45 urine samples from cats and dogs with urinary tract infections were cultured. Every bacterial isolate was tested in vitro using both Epsilometer (doxycycline and tetracycline) and disc diffusion (doxycycline, tetracycline or amoxycillin-clavulanate) tests. RESULTS: Serum doxycycline concentrations in sera of cats and dogs at 2 h were 4.2 +/- 1.0 mg/mL and 3.4 +/- 1.1 mg/mL, respectively. The corresponding concentrations at 4 h were 3.5 +/- 0.7 mg/mL and 2.8 +/- 0.6 mg/mL. Urinary doxycycline concentrations at 4 h (53.8 +/- 24.4 mg/mL for cats and 52.4 +/- 24.1 mg/mL for dogs) were substantially higher than corresponding serum values. Serum tetracycline concentrations in dogs at 2 and 4 h, and in urine at 4 h, were 6.8 +/- 2.8, 5.4 +/- 0.8, 144.8 +/- 39.4 mg/mL, respectively. Most of the urinary tract pathogens (35/45) were susceptible to urinary concentrations of doxycycline and 38/45 were susceptible to tetracycline. In contrast 41/45 of all isolates were susceptible to amoxycillin-clavulanate. CONCLUSION: This is the first report of urinary concentrations of doxycycline after conventional oral administration. Concentrations attained in the urine of normal cats and dogs were sufficient to inhibit the growth of a significant number of urinary tract pathogens and thus doxycycline may be a useful antimicrobial agent for some urinary tract infections.

Inclusive quarkonium production at forward rapidity in pp collisions at [Formula: see text]TeV.

We report on the inclusive production cross sections of [Formula: see text], [Formula: see text], [Formula: see text](1S), [Formula: see text](2S) and [Formula: see text](3S), measured at forward rapidity with the ALICE detector in [Formula: see text] collisions at a center-of-mass energy [Formula: see text] TeV. The analysis is based on data collected at the LHC and corresponds to an integrated luminosity of 1.23 pb[Formula: see text]. Quarkonia are reconstructed in the dimuon-decay channel. The differential production cross sections are measured as a function of the transverse momentum [Formula: see text] and rapidity y, over the [Formula: see text] ranges [Formula: see text] GeV/c for [Formula: see text], [Formula: see text] GeV/c for all other resonances, and for [Formula: see text]. The cross sections, integrated over [Formula: see text] and y, and assuming unpolarized quarkonia, are [Formula: see text] [Formula: see text]b, [Formula: see text] [Formula: see text]b, [Formula: see text] nb, [Formula: see text] nb and [Formula: see text] nb, where the first uncertainty is statistical and the second one is systematic. These values agree, within at most [Formula: see text], with measurements performed by the LHCb collaboration in the same rapidity range.

Centrality dependence of charged jet production in p-Pb collisions at [Formula: see text] = 5.02 TeV.

Measurements of charged jet production as a function of centrality are presented for  p-Pb  collisions recorded at [Formula: see text] TeV with the ALICE detector. Centrality classes are determined via the energy deposit in neutron calorimeters at zero degree, close to the beam direction, to minimise dynamical biases of the selection. The corresponding number of participants or binary nucleon-nucleon collisions is determined based on the particle production in the Pb-going rapidity region. Jets have been reconstructed in the central rapidity region from charged particles with the anti-[Formula: see text] algorithm for resolution parameters [Formula: see text] and [Formula: see text] in the transverse momentum range 20 to 120 GeV/c. The reconstructed jet momentum and yields have been corrected for detector effects and underlying-event background. In the five centrality bins considered, the charged jet production in  p-Pb   collisions is consistent with the production expected from binary scaling from pp collisions. The ratio of jet yields reconstructed with the two different resolution parameters is also independent of the centrality selection, demonstrating the absence of major modifications of the radial jet structure in the reported centrality classes.

Production of K[Formula: see text](892)[Formula: see text] and [Formula: see text](1020) in p-Pb collisions at [Formula: see text] = 5.02 TeV.

The production of K[Formula: see text](892)[Formula: see text] and [Formula: see text](1020) mesons has been measured in p-Pb collisions at [Formula: see text][Formula: see text] 5.02 TeV. K[Formula: see text] and [Formula: see text] are reconstructed via their decay into charged hadrons with the ALICE detector in the rapidity range [Formula: see text]. The transverse momentum spectra, measured as a function of the multiplicity, have a p[Formula: see text] range from 0 to 15 GeV/c for K[Formula: see text] and from 0.3 to 21 GeV/c for [Formula: see text]. Integrated yields, mean transverse momenta and particle ratios are reported and compared with results in pp collisions at [Formula: see text][Formula: see text] 7 TeV and Pb-Pb collisions at [Formula: see text][Formula: see text] 2.76 TeV. In Pb-Pb and p-Pb collisions, K[Formula: see text] and [Formula: see text] probe the hadronic phase of the system and contribute to the study of particle formation mechanisms by comparison with other identified hadrons. For this purpose, the mean transverse momenta and the differential proton-to-[Formula: see text] ratio are discussed as a function of the multiplicity of the event. The short-lived K[Formula: see text] is measured to investigate re-scattering effects, believed to be related to the size of the system and to the lifetime of the hadronic phase.

Multiplicity and transverse momentum evolution of charge-dependent correlations in pp, p-Pb, and Pb-Pb collisions at the LHC.

We report on two-particle charge-dependent correlations in pp, p-Pb, and Pb-Pb collisions as a function of the pseudorapidity and azimuthal angle difference, [Formula: see text] and [Formula: see text] respectively. These correlations are studied using the balance function that probes the charge creation time and the development of collectivity in the produced system. The dependence of the balance function on the event multiplicity as well as on the trigger and associated particle transverse momentum ([Formula: see text]) in pp, p-Pb, and Pb-Pb collisions at [Formula: see text] 7, 5.02, and 2.76 TeV, respectively, are presented. In the low transverse momentum region, for [Formula: see text] GeV/c, the balance function becomes narrower in both [Formula: see text] and [Formula: see text] directions in all three systems for events with higher multiplicity. The experimental findings favor models that either incorporate some collective behavior (e.g. AMPT) or different mechanisms that lead to effects that resemble collective behavior (e.g. PYTHIA8 with color reconnection). For higher values of transverse momenta the balance function becomes even narrower but exhibits no multiplicity dependence, indicating that the observed narrowing with increasing multiplicity at low [Formula: see text] is a feature of bulk particle production.

Clinical and immune responses in advanced melanoma patients immunized with an anti-idiotype antibody mimicking disialoganglioside GD2.

PURPOSE: To determine immune responses and toxicity to the anti-idiotype vaccine, as well as clinical responses and survival, we initiated a clinical trial for patients with advanced melanoma treated with an anti-idiotype antibody (TriGem) that mimics the disialoganglioside GD2. PATIENTS AND METHODS: Forty-seven patients with advanced melanoma received either 1-, 2-, 4-, or 8-mg doses of TriGem (Titan Pharmaceuticals Inc, South San Francisco, CA) mixed with QS-21 adjuvant (Aquila Biopharmaceuticals, Inc, Worcester, MA) 100 microg subcutaneously weekly for 4 weeks and then monthly until disease progression. Median age was 57 years, there were 32 men and 15 women, 43% of patients had undergone prior therapy for metastatic disease, 55% had disease confined to soft tissue, and 45% had visceral metastasis. RESULTS: Hyperimmune sera from 40 of 47 patients showed an anti-anti-idiotype (Ab3) response. Patient Ab3 was truly Ab1' because it specifically bound purified disialoganglioside GD2. The isotypic specificity of the Ab3 antibody consisted of predominantly immunoglobulin (Ig)G, and all IgG subclasses were represented. One patient had a complete response that persisted at 24 months, and 12 patients were stable from 14+ to 37+ months (median, 18+ months). Disease progression occurred in 32 patients on study from 1 to 17 months (median, 5.5 months), and 21 have died at 1 to 16 months (median, 6 months). The Kaplan-Meier-derived overall median survival has not been reached. Median survival has not been reached for the 26 patients with soft tissue disease only and was 13 months for 21 patients with visceral metastasis. Toxicity consisted of local reaction at the site of injection and mild fever and chills. CONCLUSION: TriGem has minimal toxicity and generates robust and specific IgG immune responses against GD2. Objective responses were minimal, but there may be a favorable impact on disease progression and survival that will require prospective randomized trials.

Antibody responses in melanoma patients immunized with an anti-idiotype antibody mimicking disialoganglioside GD2.

We initiated a clinical trial for patients with advanced malignant melanoma treated with an anti-idiotype antibody that mimics the disialoganglioside GD2. We report the clinical and immune responses of the first 12 patients entered into this trial. Patients received 1-, 2-, 4-, or 8-mg doses of the anti-idiotype antibody mixed with 100 microg of QS-21 adjuvant every other week, four times, and then monthly. Twelve patients have been on trial for 2-23 months, and all of them have generated immune responses. Patients were removed from the study if they demonstrated disease progression. Hyperimmune sera from all 12 patients revealed an anti-anti-idiotypic Ab3 response, as demonstrated by the inhibition of Ab2 binding to Ab1 by patients' immune sera. To further test the anti-anti-idiotypic response, patients' Ab3 antibodies were affinity purified on Sepharose 4B columns containing adsorbed immunizing anti-idiotype immunoglobulin. Purified Ab3 of all patients studied inhibited binding of Ab1 to a GD2-positive cell line. Purified Ab3 also inhibited binding of Ab1 to purified GD2, in a manner comparable to equal quantities of purified Ab1. The patient Ab3 was truly an Ab1' because it specifically bound to purified disialoganglioside GD2. The isotypic specificity of the Ab3 antibody was predominantly IgG, with only minimal IgM. The predominant IgG subclass was IgG1, with approximately equal quantities of IgG2, IgG3, and IgG4. These Ab3 antibodies reacted specifically with tumor cells expressing GD2 by immune flow cytometry and immunoperoxidase assays. Five patients' Ab3 antibodies studied for antibody-dependent cellular cytotoxicity were positive. One patient had a complete clinical response, with resolution of soft tissue disease, and six patients had stable disease, ranging from 9 to 23 months, and are being continued on vaccine therapy. Toxicity consisted of local reaction at the site of the injection, including induration and pain that generally resolved within a few days. Mild fever and chills were observed in 75% of the patients but rarely required acetaminophen. There was no additional toxicity, including abdominal pain that was previously seen with infusion of murine monoclonal anti-GD2 antibody. Current trials include patients with stage III melanoma and small cell lung cancer. Future trials will attempt to enhance the antitumor response by the addition of interleukin 2, granulocyte macrophage colony-stimulating factor, and other cytokines, together with the 1A7 vaccine.

Clinicopathological findings associated with feline infectious peritonitis in Sydney, Australia: 42 cases (1990-2002).

OBJECTIVES: To review the clinicopathological findings in naturally-occurring, histopathologically confirmed cases of feline infectious peritonitis in client-owned cats in Sydney, Australia, with the purpose of identifying factors assisting in the diagnosis of this complex disease syndrome and to characterise the disease as it occurs in this region. DESIGN: Retrospective clinical study: the clinical records of all cats with histopathologically confirmed feline infectious peritonitis at the University Veterinary Centre Sydney and a private cat hospital in Sydney between 1990 and 2002 were reviewed for signalment, history, physical findings, diagnostic test results and the distribution of histological lesions throughout the body at necropsy. RESULTS: Forty-two cats met the inclusion criteria. Significant features of this study that unique to the contemporary literature are i) the over-representation of certain breeds (Burmese, Australian Mist, British Shorthaired, and Cornish Rex) and the under-representation of other breeds (Domestic Shorthaired, Persian); ii) the overrepresentation of males; iii) the tendency for effusive disease in Australian Mist cats and non-effusive disease in Burmese; iv) the even age distribution of disease seen in cats older than 2 years-of-age; and v) the presence of fulminant immune-mediated haemolytic anaemia in two cats in this study. CONCLUSION: The study highlights the diverse range of clinical manifestations and the complexities experienced by clinicians in diagnosing this fatal disease. Some aspects of the epidemiology and clinical manifestations of feline infectious peritonitis appear different to the disease encountered in Europe and North America, most notably the over-representation of specific breeds and the presence of immune-mediated haemolytic anaemia.

In vitro and in vivo evaluation of 2-chloroethylnitrosourea derivatives as antitumor agents.

AIM: To evaluate potential of Naphthal-NU, Napro-NU and 5-Nitro-naphthal-NU, 2-chloroethylnitrosourea compounds with substituted naphthalimide in the pre-clinical studies. MATERIALS AND METHODS: In vitro cytotoxicity of three nitrosoureas was determined in human and mouse tumor cell lines by MTT assays. In vivo anti-tumor potential was evaluated in Sarcoma-180 (S-180) and Ehrlich's carcinoma (EC) solid tumors. Apoptosis in S-180 cells was analyzed by using Annexin V-Propidium Iodide (PI). Histological analysis of liver and kidney was performed at optimum dose (50 mg/kg). Expression status of CD4(+), CD8(+) and CD25(+) cells in treated mouse were also examined. RESULTS: Significant tumor growth retardation by the compounds was noted in early and advanced disease groups, as the life span of drug treated mice increased considerably. Drug induced killing was observed by induction of apoptosis. Naphthal-NU and 5-Nitro-naphthal-NU were effective to normalize the tumor induced structural abnormalities of liver and kidney. The compounds have no immunotoxic effect on CD4(+) and CD8(+) T cells and down regulate CD4(+)CD25(+) regulatory T cells. CONCLUSION: Overall data holds promise for the antitumor activity with lower toxicity of the compounds that can be utilized for the treatment of human malignant tumors.