Metastatic cholangiocellular carcinoma and renal adenocarcinoma in a golden eagle (Aquila chrysaetos)

A 33-year-old captive male golden eagle (Aquila chrysaetos) was presented for necropsy with a history of emaciation and depression. The liver was severely distorted by numerous, coalescent, poorly demarcated, white firm nodules. Upon microscopic examination, these masses were found to be infiltrative and were composed of anastomosing tubular structures lined by signet-ring cells piling up in a disorderly fashion. Ultrastructurally, neoplastic cells were characterized by abundant microvilli at their apical pole and by numerous junctional complexes on lateral cell membranes. Based on morphological criteria, this tumour was classified as a poorly differentiated cholangiocellular carcinoma. Metastases were found in kidneys, testes, lungs, air sacs, pericardium, pancreas, adrenals and meninges. Additionally, two (11 and 2 mm) beige nodules were found in the cranial portion of the left kidney. Histological examination revealed locally infiltrative compact masses composed of well-differentiated tubules lined by a tall columnar epithelium without microvilli. These tumours were diagnosed as renal tubular adenocarcinomas. This is believed to be the first case of two simultaneous malignancies reported in a bird of prey.     

SarCNU, a nitrosourea analog on a day 1, 5, and 9 oral schedule: a phase I and pharmacokinetic study in patients with advanced solid tumors.

PURPOSE: 2-Chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU) is a novel chloroethylnitrosourea that demonstrates selective cytotoxicity in athymic mice bearing human glioma. SarCNU demonstrates selective cytotoxicity in vitro against human glioma at least in part because of the selective SarCNU uptake by the extraneuronal monoamine transporter. The purpose of this phase I study was to determine the maximum-tolerated dose (MTD), the toxicity profile, the pharmacokinetics profile, and recommended phase II dose. PATIENTS AND METHODS: Forty-three eligible patients with advanced solid tumors were enrolled. SarCNU was administered orally on days 1,5, and 9 every 28 days. The dose ranged from 30 to 1,075 mg/m2. Pharmacokinetic evaluation was done on the first cycle (one dose was given intravenously on day 1 or 5 of the first cycle to determine bioavailability). RESULTS: Delayed myelosuppression (thrombocytopenia and neutropenia occurring 4 to 6 weeks after administration) was the dose-limiting toxicity (DLT). Anemia occurred but was mild. Nonhematologic toxicity was generally mild, but one patient died with pulmonary toxicity that was probably secondary to SarCNU. There were no partial or complete responses, but eight patients had stable disease for 19 to 46 weeks. The oral bioavailability of SarCNU was 80% +/- 37%. The terminal phase half-life was similar after intravenous (58.4 +/- 23.5 minutes) or oral (64.0 +/- 34.8 minutes) administration. The total plasma clearance was 20.4 +/- 8.8 L/h/m2, and the apparent volume of distribution was 29.9 +/- 17.6 L/m2. The area under the plasma concentration-time profile increased proportionally with the dose, and the pharmacokinetics seemed to be independent of the route of administration and the number of doses. CONCLUSION: SarCNU was well tolerated and the MTD was 1,075 mg/m2. The recommended starting dose for phase II trials is 860 mg/m2 orally on days 1, 5, and 9 every 6 weeks.     

Does the Lateral Chest Radiograph Help Pediatric Emergency Physicians Diagnose Pneumonia? A Randomized Clinical Trial

OBJECTIVES: To determine whether the addition of the lateral chest radiograph to the frontal view influences the pediatric emergency physician's diagnosis and management of patients with pneumonia. METHODS: A randomized clinical trial was conducted, involving 570 patients, 1-16 years of age, visiting a pediatric emergency department (ED) for whom frontal and lateral chest radiographs were ordered for the clinical suspicion of pneumonia. Pediatric emergency physicians reviewed the frontal film alone in group 1 and both the frontal and the lateral films in group 2. The interpretation of each radiograph was then compared with consensus interpretation by pediatric radiologists who interpreted both views. RESULTS: There were 604 eligible children; 34 families declined to participate. Three hundred three were randomized into group 1, whereas 267 were randomized into group 2. The clinicians' interpretations were equal in sensitivity for group 1 at 91% and 87% in group 2 (p = 0.321) and equal in specificity for group 1 at 58% and 57% in group 2 (p = 0.888). CONCLUSIONS: The addition of the lateral chest radiograph to the frontal view did not improve the sensitivity or specificity of pediatric emergency physicians in their diagnosis of pneumonia in children.     

Malnutrition at Hospital Admission—Contributors and Effect on Length of Stay

Background: In hospitals, length of stay (LOS) is a priority but it may be prolonged by malnutrition. This study seeks to determine the contributors to malnutrition at admission and evaluate its effect on LOS. Materials and Methods: This is a prospective cohort study conducted in 18 Canadian hospitals from July 2010 to February 2013 in patients ≥ 18 years admitted for ≥ 2 days. Excluded were those admitted directly to the intensive care unit; obstetric, psychiatry, or palliative wards; or medical day units. At admission, the main nutrition evaluation was subjective global assessment (SGA). Body mass index (BMI) and handgrip strength (HGS) were also performed to assess other aspects of nutrition. Additional information was collected from patients and charts review during hospitalization. Results: One thousand fifteen patients were enrolled: based on SGA, 45% (95% confidence interval [CI], 42%–48%) were malnourished, and based on BMI, 32% (95% CI, 29%–35%) were obese. Independent contributors to malnutrition at admission were Charlson comorbidity index > 2, having 3 diagnostic categories, relying on adult children for grocery shopping, and living alone. The median (range) LOS was 6 (1–117) days. After controlling for demographic, socioeconomic, and disease‐related factors and treatment, malnutrition at admission was independently associated with prolonged LOS (hazard ratio, 0.73; 95% CI, 0.62–0.86). Other nutrition‐related factors associated with prolonged LOS were lower HGS at admission, receiving nutrition support, and food intake < 50%. Obesity was not a predictor. Conclusion: Malnutrition at admission is prevalent and associated with prolonged LOS. Complex disease and age‐related social factors are contributors.     

Genetic interaction between members of the Vangl family causes neural tube defects in mice

Neural tube defects (NTDs) are very frequent congenital abnormalities in humans. Recently, we have documented independent association of Vangl1 and Vangl2 gene mutations with NTDs. In the Looptail mouse, homozygosity (but not heterozygosity) for loss-of-function alleles at Vangl2 causes the severe NTD craniorachischisis, whereas heterozygosity for mutant variants of VANGL1 is associated with NTDs in a human cohort of sporadic and familial cases. To understand the role of Vangl1 in normal development, we created a mouse mutant with an inactivating mutation at Vangl1 (Vangl1(gt)). Vangl1 shows a dynamic pattern of expression in the developing neural tube and notochord at the time of neural tube closure. Vangl1(gt/+) heterozygotes and Vangl1(gt/gt) homozygotes are viable and fertile, although Vangl1(gt/gt) display subtle alterations in polarity of inner hair cells of the cochlea. Remarkably, and as opposed to healthy Vangl1(gt/+) and Vangl2(lp/+) heterozygotes, Vangl1(gt/+);Vangl2(lp/+) double heterozygotes show profound developmental defects that include severe craniorachischisis, inner ear defects (disorganization of the stereociliary bundles of hair cells of the organ of Corti), and cardiac abnormality (aberrant right subclavian artery). These results show that genetic interaction between Vangl1 and Vangl2 genes causes neural tube defects and raise the possibility that interaction between individual Vangl genes and other genetic loci and/or environmental factors may additionally contribute to the etiology of NTDs.     

Large hepatic mesenchymal hamartoma leading to mid-trimester fetal demise

This report describes a fetus with a large multiloculated cystic liver mass. Two small abdominal cysts were seen on ultrasound at 19 weeks of gestation but the patient was referred to us at 23 weeks, after the mass had grown to 8.0 x 5.6 x 7.0 cm, displacing intra-abdominal organs, heart and diaphragm. There was a small amount of ascites but no hydrops. There was polyhydramnios and a thick hyperechoic placenta. After detailed sonograms and MRI suggested the diagnosis of cystic mesenchymal hamartoma of the liver, cyst decompression was favored and consent was obtained. Unfortunately, absence of fetal cardiac activity was noted on the day of the planned intervention. Autopsy confirmed the diagnosis and demonstrated placental changes consistent with mesenchymal stem villous hyperplasia of the placenta. Large fetal cystic abdominal masses that compress the heart, lungs and other organs may benefit from prenatal decompression. This is the first report of cystic hamartoma of the liver apparent on second-trimester sonography, and the fourth time such a lesion is associated with fetal or neonatal death out of 11 cases diagnosed prenatally.     

Is chromium an important element in HIV-positive patients with metabolic abnormalities? An hypothesis generating pilot study

BACKGROUND: Chromium plays a role in insulin sensitivity. OBJECTIVES: To compare chromium measurements in HIV-positive patients with or without (N) antiretroviral therapy (ART) to that of healthy controls (HC) and, to determine if there is any association between chromium levels and abnormalities in body composition, glucose and lipid metabolism. DESIGN: A cross-sectional study in 91 HIV patients (75 HIV-ART, 16 HIV-N) and 13 HC. Chromium was assessed in the diet, plasma, toenails, and urine. Fasting blood glycemia and lipids, lipodystrophy score and body fat were also determined. RESULTS: Dietary intake of chromium was similar in the 3 groups. Plasma and toenail Cr were lower in HIV compared to HC, but urinary chromium was similar. However, when the HIV-positive patients on ART were compared to those who were na?ve to therapies, urinary excretion of chromium was higher in HIV-ART. In addition, urinary excretion of chromium significantly and positively correlated with lipodystrophy score and negatively with various parameters of metabolic syndrome. CONCLUSION: Despite a similar dietary intake, chromium levels were lower in HIV-positive patients and urinary chromium excretion correlated with some metabolic parameters. Low chromium levels may be due to increased chromium losses. These results support further studies on chromium in HIV patients.     

Asthma-COPD Overlap Phenotypes and Smoking :Comparative features of asthma in smoking or non-smoking patients with an incomplete reversibility of airway obstruction

ABSTRACT

The development of COPD features, such as an incomplete reversibility of airway obstruction (IRAO), in smoking or non-smoking asthmatic patients, a condition often named Asthma-COPD Overlap (ACO), has been recognized for decades. However, there is a need to know more about the sub-phenotypes of this condition according to smoking.

This study aimed at comparing the clinical, physiological and inflammatory features of smoking and non-smoking asthmatic patients exhibiting IRAO.

In this cross-sectional study, patients with an IRAO with (ACO, ≥20 pack-years) or without (NS-IRAO, <5 pack-years) significant smoking history completed questionnaires about asthma control (ACQ, score 0–6, 6 = better score) and quality of life (AQLQ, score 1–7, 1 = better score) and performed expiratory flows, lung volume and carbon monoxide diffusion capacity measurements. Blood sampling and induced sputum were obtained for systemic and lower airway inflammation assessment.

A total of 115 asthmatic patients were included (75 ACO: age 61 ± 10 years, 60% women and 40 NS-IRAO: age 64 ± 9 years, 38% women). ACO patients had worse asthma control scores (1.8 ± 0.9 vs 1.4 ± 0.9, P = 0.02) and poorer asthma quality of life (5.3 ± 1.0 vs 5.9 ± 1.0, P = 0.003). In addition, ACO had higher residual volume (145 ± 45 vs 121 ± 29% predicted, P = 0.008) and a lower carbon monoxide diffusing capacity corrected for alveolar volume (90 ± 22 vs 108 ± 20% predicted, P = 0.0008). No significant differences were observed in systemic or lower airway inflammation.

In conclusion, in smokers and non-smokers, the presence of IRAO in asthmatics is associated with different phenotypes that reflect the addition of smoking-induced changes to asthma physiopathology.     

Burn injury induces a change in T cell homeostasis affecting preferentially CD4+ T cells

Burn injuries are known to be associated with altered immune functions, resulting in decreased resistance to subsequent infection. In the present study, we determined the in vivo changes in T cell homeostasis following burn injury. Two groups of mice were used: a sham-burn group receiving buprenorphine as an analgesic and a burn group receiving buprenorphine and subjected to burn injury on 20% of the total body surface area. Results showed an important decrease in splenocytes following burn injury. This decrease persisted for 5 days and was followed, at day 10, by a 63% increase in number of cells. In vivo cell proliferation, as determined by the incorporation of 5-bromo-2'-dexoxyuridine, showed a significant increase of cycling splenocytes between days 2 and 10 after burn injury. The percentage of CD4+ and CD8+ T cells in the spleen was altered for 10 days after thermal injury. Analysis of naive (CD62Lhigh CD44low) and effector/memory (CD62Llow CD44high) T cells showed a percent decrease, independent of the expression of CD4 or CD8 molecules. However, early activation markers, such as CD69+, were expressed only on CD4+ T cells after a number of days following injury. Even with an activated phenotype, 10 days post-burn injury, CD4+ naive T cells significantly increased spontaneous apoptosis, detected by using a fluorescent DNA-binding agent 7-amino-actinomycin D. CD8+ T lymphocytes did not express early activation markers and were more resistant to apoptosis. Using purified T cells, we have shown unresponsiveness at day 10. Overall, these results demonstrate that mechanisms of T cell homeostasis were perturbed following burn injury. However, after 10 days, this perturbation persisted only in CD4+ T cells.