Renal cell carcinoma uvula metastasis leading to airway compromise: an unusual site.

We present a case report of a gentleman presenting with a globular lesion arising from his uvula. Although elective admission was planned, he presented with airway compromise, and emergency excision was required. The patient had a background of metastatic clear cell renal carcinoma; histology confirmed the uvula lesion as a further secondary deposit. Renal cell carcinoma has a recognised metastatic propensity, but spread to the uvula is rare, with only two previously described cases in the literature. This case is notable for the unusual location of the metastasis, as well as the rapid progression of symptoms, which threatened the airway and necessitated urgent surgical intervention.

Unusual metachronous presentation of bilateral frontoethmoid sinus mucoceles.

A case report of a patient with bilateral frontoethmoid mucoceles with no obvious predisposing factors and each side presenting three years apart, with no ongoing nasal or paranasal signs of disease in the interim.Bilateral paranasal sinus mucoceles have rarely been described in the literature; this case is unique, as it is the first description of a metachronous presentation. Additionally, the absence of any predisposing factors such as trauma, surgery or chronic sinusitis in either presentation is unusual.

Metabolomic Profiling of the Synergistic Effects of Melittin in Combination with Cisplatin on Ovarian Cancer Cells.

Melittin, the main peptide present in bee venom, has been proposed as having potential for anticancer therapy; the addition of melittin to cisplatin, a first line treatment for ovarian cancer, may increase the therapeutic response in cancer treatment via synergy, resulting in improved tolerability, reduced relapse, and decreased drug resistance. Thus, this study was designed to compare the metabolomic effects of melittin in combination with cisplatin in cisplatin-sensitive (A2780) and resistant (A2780CR) ovarian cancer cells. Liquid chromatography (LC) coupled with mass spectrometry (MS) was applied to identify metabolic changes in A2780 (combination treatment 5 µg/mL melittin + 2 µg/mL cisplatin) and A2780CR (combination treatment 2 µg/mL melittin + 10 µg/mL cisplatin) cells. Principal components analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) multivariate data analysis models were produced using SIMCA-P software. All models displayed good separation between experimental groups and high-quality goodness of fit (R²) and goodness of prediction (Q²), respectively. The combination treatment induced significant changes in both cell lines involving reduction in the levels of metabolites in the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, purine and pyrimidine metabolism, and the arginine/proline pathway. The combination of melittin with cisplatin that targets these pathways had a synergistic effect. The melittin-cisplatin combination had a stronger effect on the A2780 cell line in comparison with the A2780CR cell line. The metabolic effects of melittin and cisplatin in combination were very different from those of each agent alone.

Metabolomic Profiling of the Effects of Melittin on Cisplatin Resistant and Cisplatin Sensitive Ovarian Cancer Cells Using Mass Spectrometry and Biolog Microarray Technology.

In the present study, liquid chromatography-mass spectrometry (LC-MS) was employed to characterise the metabolic profiles of two human ovarian cancer cell lines A2780 (cisplatin-sensitive) and A2780CR (cisplatin-resistant) in response to their exposure to melittin, a cytotoxic peptide from bee venom. In addition, the metabolomics data were supported by application of Biolog microarray technology to examine the utilisation of carbon sources by the two cell lines. Data extraction with MZmine 2.14 and database searching were applied to provide metabolite lists. Principal component analysis (PCA) gave clear separation between the cisplatin-sensitive and resistant strains and their respective controls. The cisplatin-resistant cells were slightly more sensitive to melittin than the sensitive cells with IC50 values of 4.5 and 6.8 µg/mL respectively, although the latter cell line exhibited the greatest metabolic perturbation upon treatment. The changes induced by melittin in the cisplatin-sensitive cells led mostly to reduced levels of amino acids in the proline/glutamine/arginine pathway, as well as to decreased levels of carnitines, polyamines, adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD+). The effects on energy metabolism were supported by the data from the Biolog assays. The lipid compositions of the two cell lines were quite different with the A2780 cells having higher levels of several ether lipids than the A2780CR cells. Melittin also had some effect on the lipid composition of the cells. Overall, this study suggests that melittin might have some potential as an adjuvant therapy in cancer treatment.

The hormonal response of older men to sub-maximum aerobic exercise: the effect of training and detraining.

The hormonal response of 32 older men (70-80years) to a bout of sub-maximum aerobic exercise was examined before, after 16weeks of resistance or aerobic training and again after 4weeks of detraining. Blood samples were obtained at rest and immediately post sub-maximum exercise (30min @ 70% VO(2) max) to determine the concentrations of growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone (Test), sex hormone-binding globulin (SHBG) and the calculation of free testosterone (FT). Both training groups had significant increases in leg strength and VO(2) max after 16weeks training but leg strength and VO(2) max returned to pre-training levels in the aerobic training and resistance training groups, respectively. During the 20week study there was no change in resting concentrations of any hormones among the three groups. There was no increase in GH, IGF-1 or SHBG immediately post sub-maximum exercise in any of the groups before training, after 16weeks training or after 4weeks detraining. Testosterone and FT increased immediately post sub-maximum exercise within all groups before training, after 16weeks training and after 4weeks detraining with the increase in Test and FT higher after 16weeks of resistance training compared to before training and after 4weeks detraining within the resistance training group. The increased responsiveness of Test and FT after 16weeks of resistance training was lost after 4weeks of detraining. Our results indicate that some physiological and hormonal adaptations gained after 16weeks training are lost after only 4weeks detraining.

Population characteristics of feral cats admitted to seven trap-neuter-return programs in the United States.

Internationally, large populations of feral cats constitute an important and controversial issue due to their impact on cat overpopulation, animal welfare, public health, and the environment, and to disagreement about what are the best methods for their control. Trap-neuter-return (TNR) programs are an increasingly popular alternative to mass euthanasia. The objective of this study was to determine the population characteristics of feral cats admitted to large-scale TNR programs from geographically diverse locations in the United States. Data from 103,643 feral cats admitted to TNR programs from 1993 to 2004 were evaluated. All groups reported more intact females (53.4%) than intact males (44.3%); only 2.3% of the cats were found to be previously sterilized. Overall, 15.9% of female cats were pregnant at the time of surgery. Pregnancy was highly seasonal and peaked between March and April for all of the groups. The average prenatal litter size was 4.1+/-0.1 fetuses per litter. Cryptorchidism was observed in 1.3% of male cats admitted for sterilization. A total of 0.4% of cats was euthanased because of the presence of debilitating conditions, and 0.4% died during the TNR clinics. Remarkably similar populations of cats with comparable seasonal variability were seen at each program, despite their wide geographical distribution. These results suggest that it is feasible to safely sterilize large numbers of feral cats and that the experiences of existing programs are a consistent source of information upon which to model new TNR programs.

GH treatment in adults with chronic liver disease: a randomized, double-blind, placebo-controlled, cross-over study.

Patients with chronic liver disease (CLD) are catabolic and GH-resistant. The effects of supraphysiological recombinant human GH (rhGH; 0.2 IU.kg(-1).d(-1)) treatment in adults with CLD were assessed in a randomized, double-blind, placebo-controlled cross-over trial (4-wk dietary run-in, 4-wk treatment, and 2-wk wash-out phases). Nine adults with mild- to moderate-severity CLD participated (median age, 49 yr; three males and six females; Child's classification A in six and B in three). Biopsy-proven etiologies were: alcohol (four patients), primary biliary cirrhosis (three patients), non-A, non-B, non-C hepatitis (one patient), and cryptogenic (one patient). Treatment with rhGH increased serum IGF-I (median increase over placebo, +93 microg.liter(-1); P = 0.004), IGF-binding protein-3 (+0.9 mg.liter(-1): P = 0.004), and acid labile subunit (+10.7 nM; P = 0.004). Total body potassium (+8.0 g; P = 0.023), body weight (+1.6 kg; P = 0.008), and total body water (by bioelectrical impedance; +4.9 kg; P = 0.004) increased. Resting metabolic rate (+313 ml.kg(-1).min(-1); P = 0.004) and lipid oxidation (+1072.0 kcal.d(-1); P = 0.032) increased. Metabolic changes included increased fasting plasma glucose (+1.2 mM; P = 0.008), insulin (+33.8 mU.liter(-1); P = 0.004), C-peptide (+0.7 nM; P = 0.004), and free-fatty acids (+0.1 mEq.liter(-1); P = 0.04). Clinical side effects included worsening edema and ascites. Hepatocellular function did not change. Therefore, rhGH treatment in CLD: 1) overcame hepatic GH resistance; 2) may have improved whole-body protein catabolism; 3) increased lipolysis and lipid oxidation; 4) increased insulin resistance; and 5) had potent antinatriuretic effects. Long-term safety and efficacy require further assessment.