Background: Liposomal cisplatin is a new formulation developed to reduce the systemic toxicity of cisplatin while simultaneously improving the targeting of the drug to the primary tumor and to metastases by increasing circulation time in the body fluids and tissues. The primary objectives were to determine nephrotoxicity, gastrointestinal side-effects, peripheral neuropathy and hematological toxicity and secondary objectives were to determine the response rate, time to tumor progression (TTP) and survival.Patients and methods: Two hundred and thirty-six chemotherapy-naive patients with inoperable non-small-cell lung cancer were randomly allocated to receive either 200 mg/m2 of liposomal cisplatin and 135 mg/m2 paclitaxel (arm A) or 75 mg/m2 cisplatin and 135 mg/m2 paclitaxel (arm B), once every 2 weeks on an outpatient basis. Two hundred and twenty-nine patients were assessable for toxicity, response rate and survival. Nine treatment cycles were planned.Results: Arm A patients showed statistically significant lower nephrotoxicity, grade 3 and 4 leucopenia, grade 2 and 3 neuropathy, nausea, vomiting and fatigue. There was no significant difference in median and overall survival and TTP between the two arms; median survival was 9 and 10 months in arms A and B, respectively, and TTP was 6.5 and 6 months in arms A and B, respectively.Conclusions: Liposomal cisplatin in combination with paclitaxel has been shown to be much less toxic than the original cisplatin combined with paclitaxel. Nephrotoxicity in particular was negligible after liposomal cisplatin administration. TTP and survival were similar in both treatment arms.

Post-prandial serum bile acid concentrations were measured in 200 Maltese dogs in an attempt to identify those with subclinical portosystemic shunts. Five of these were later shown to have hepatic pathology or abnormal liver function. In the other 195 Maltese, bile acid concentrations ranged from 1 to 362 mumol.L-1 (mean +/- SD, 70 +/- 50 mumol.L-1; median, 65.0 mumol.L-1). Of these, 79% were above the reference range (0 to 31 mumol.L-1) established from 23 mixed-breed control dogs. It was therefore not possible to determine the prevalence of subclinical portosystemic shunts on the basis of bile acid determinations. Further investigation of liver function was performed to investigate why bile acid concentrations were increased in these dogs. Rectal ammonia tolerance tests were normal in 102 of 106 Maltese tested and liver samples (11 dogs) and plasma biochemistry profiles (9 dogs) demonstrated no significant hepatic disease or dysfunction. Of 2 Maltese with hyperammonaemia after administration of ammonium chloride, one had a large congenital portosystemic shunt that was confirmed at surgery. In the other there were no macroscopic portosystemic communications, but a liver biopsy showed histological changes consistent with microscopic portovascular dysplasia. Total serum bile acid concentrations were consistently lower when assessed by high-performance liquid chromatography than by an enzymatic spectrophotometric method. This discrepancy was substantially larger in Maltese than in control dogs, suggesting the presence of an additional reacting substance in the serum of Maltese dogs.

R Re es sp pi ir ra at to or ry y m mu us sc cl le e s st tr re en ng gt th h d du ur ri in ng g c co on nt ti in nu uo ou us s a am mb bu ul la at to or ry y p pe er ri it to on ne ea al l d di ia al ly ys si is s ( (C CA AP PD D) ) N Maximum pressures, spirometry and lung volumes were measured before dialysis, 4 h after the administration of 2 l of dialysate into the peritoneal cavity, and just after the next drainage. In addition, biochemical indices (urea, creatinine, sodium, potassium, calcium and phosphorus) and haematological indices (haemoglobin (Hb) and haematocrit (Hct)) were measured once before the treatment.The results showed that mean PImax and PEmax were normal, with a very wide range between patients, before CAPD. However, seven patients (27%) showed a PImax of <75% predicted (pred) and eight (31%) a PEmax <75% pred. Maximal pressures decreased significantly during CAPD and increased again after the drainage of fluid. Similarly, lung volumes were within the normal range before and decreased significantly during CAPD. The forced expiratory volume in one second to forced vital capacity (FEV 1 /FVC) ratio did not change.We conclude that respiratory muscle strength was preserved in the majority of the patients with chronic renal failure treated with CAPD. During CAPD, lung volumes and respiratory muscle function were decreased, demonstrating an effect of the abdominal cavity on the mechanics of the respiratory system. However, the decrease in the maximum pressures was less than 20%, indicating that CAPD is a safe procedure in patients without pre-existing pulmonary disease or uraemic pulmonary complications. Respiratory muscle strength increased immediately after the drainage of fluid.

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Spondylocostal dysostosis is a congenital disorder of the axial skeleton documented in human families from diverse racial backgrounds. The condition is characterised by truncal shortening, extensive hemivertebrae and rib anomalies including malalignment, fusion and reduction in number. Mutations in the Notch signalling pathway genes DLL3, MESP2, LFNG, HES7 and TBX6 have been associated with this defect. In this study, spondylocostal dysostosis in an outbred family of miniature schnauzer dogs is described. Computed tomography demonstrated that the condition mirrors the skeletal defects observed in human cases, but unlike most human cases, the affected dogs were stillborn or died shortly after birth. Through gene mapping and whole genome sequencing, we identified a single-base deletion in the coding region of HES7. The frameshift mutation causes loss of functional domains essential for the oscillatory transcriptional autorepression of HES7 during somitogenesis. A restriction fragment length polymorphism test was applied within the immediate family and supported a highly penetrant autosomal recessive mode of inheritance. The mutation was not observed in wider testing of 117 randomly sampled adult miniature schnauzer and six adult standard schnauzer dogs; providing a significance of association of P raw = 4.759e-36 (genome-wide significant). Despite this apparently low frequency in the Australian population, the allele may be globally distributed based on its presence in two unrelated sires from geographically distant locations. While isolated hemivertebrae have been observed in a small number of other dog breeds, this is the first clinical and genetic diagnosis of spontaneously occurring spondylocostal dysostosis in a non-human mammal and offers an excellent model in which to study this devastating human disorder. The genetic test can be utilized by dog breeders to select away from the disease and avoid unnecessary neonatal losses.

Measles is an acute febrile illness, potentially fatal and highly contagious, which is transmitted through the respiratory mode. Fever combined with one of the following: cough, coryza, conjunctivitis are the first manifestations of the disease. Koplik's spots may also appear on the buccal mucosa providing an opportunity to set the diagnosis even before the emergence of rash. Rash typically appears 3-4 days after the onset of fever, initially on the face and behind the ears, and its appearance is associated with the peak of the symptoms. Measles affects multiple systems, including the respiratory system, with pneumonia being one of the most lethal complications. Management involves best supportive care, correction of dehydration and nutritional deficiencies, treatment of secondary bacterial infections and provision of vitamin A. Importantly, given that measles present with lifelong immunity following infection or vaccination, prevention through measles vaccination has a cardinal role for measles' elimination. Indeed, public education and vaccination led to an estimated 79% decrease in global measles deaths from 2000 to 2015. Nonetheless, the last two years have seen a measles outbreak in several countries, partially due to the anti-vaccination movement. This article aims to present two cases of measles in our hospital and highlight the pressing need for vaccination in order to eradicate a potentially fatal disease.

Introduction: Exacerbations are critical events in the course of asthma and chronic obstructive pulmonary disease (COPD). These events are potentially life-threatening, and the studies have shown that they have tremendous implications on long-term disease control and the overall prognosis of the patients. The aim of this study was to examine adipokines, cytokines and C-reactive protein (CRP) as potential biomarkers in asthma and COPD. Material and methods: Prospective cohort study of COPD and asthma patients treated for acute exacerbations. Thirty-nine COPD patients and 15 asthmatic patients were included in the study. Leptin, adiponectin, resistin, interleukin (Il)-6, 8, 18, tumor necrosis factor-a (TNF-a), and CRP were measured at three time points: on admission, at resolution and at the stable phase. Pre-and post-bronchodilation spirometry was additionally performed at resolution and at the stable phase. Results: In COPD patients, leptin, leptin/adiponectin (L/A) ratio and resistin were elevated on admission compared to the stable phase. In asthmatic patients, leptin levels were raised on admission compared to the stable phase, and adiponectin was elevated at resolution compared to admission. In both diseases, CRP was significantly increased on admission compared to both resolution and stable disease. Finally, TNF-a could distinguish between asthma and COPD stable phase. Conclusions: Leptin and CRP levels may be useful biomarkers in monitoring COPD and asthma response to treatment during an exacerbation episode. Hypoadiponectinemia was detected in asthma and COPD during all stages of the diseases. TNF-a could distinguish between asthma and COPD stable phase.

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