Mutagenicity and genotoxicity of ClearTaste.

The present study investigates whether ClearTaste is mutagenic/genotoxic by employing it as a test article in bacterial reverse mutation (Ames test) and in vitro human peripheral blood lymphocyte micronucleus assays conducted by a Good Laboratory Practice certified third party as parameterized by the United States Food and Drug Administration. ClearTaste is a taste modulator derived from the filtrate of submerged Cordyceps sinensis and is typically processed into a powder. It functions as a bitter, sour, astringency, metallic and lingering aftertaste mitigator/blocker. The Ames test includes revertant colony counts almost exclusively less than 100/plate and significantly fewer ClearTaste counts as opposed to known mutagen counts. The micronucleus assay reported cytotoxicity exclusively < 25% for doses up to 2,000 µg/L with Cytokinesis Block Proliferation Indices less than water and statistically significant differences between micronucelated cells post dosing compared to cyclophosphamide and vinblastine controls. The conclusion of these data is that ClearTaste is neither muta- nor carcinogenic.

Prothrombin time and activated partial thromboplastin time using a point-of-care analyser (Abaxis VSpro®) in Bennett's wallabies (Macropus rufogriseus).

There are few reports of coagulation times in marsupial species. Blood samples collected from 14 Bennett's wallabies (Macropus rufogriseus) under anaesthesia during routine health assessments were analysed for prothrombin time (PT) and activated partial thromboplastin time (aPTT) using a point-of-care analyser (POC) (Abaxis VSPro®). The wallabies had an aPTT mean of 78.09 s and median of 78.1 s. The PT for all wallabies was greater than 35 s, exceeding the longest time measured on the POC. Although PT was significantly longer, aPTT was similar to the manufacturer's domestic canine reference range.

Morphologic evidence suggestive of hypertension in western gray kangaroos (Macropus fuliginosus).

Marked renal vascular changes, suggestive of hypertension, were present in adult western gray kangaroos (Macropus fuliginosus) from a single facility over a 14-year period. A subset of these kangaroos also had vague clinical nervous system deficits, including blindness. To characterize the vascular lesions, determine prevalence, and document other changes, case histories and archival tissue sections from 21 adult kangaroos (8 male, 13 female) that died or were euthanatized between 1994 and 2008 were reviewed. Relevant lesions included increased thickness of the renal arteriolar tunica media with smooth muscle hypertrophy and/or hyperplasia, accumulation of extracellular matrix within arterioles, increased vascular tortuosity, and varying degrees of juxtaglomerular hyperplasia. Renal tissue from two more severely affected animals was further examined by transmission electron microscopy, highlighting arteriolar endothelial cell hypertrophy and disruption of the medial architecture. Hypertrophy of arteries and arterioles in other organ systems was also present (3/21), including vessels in the brain and spinal cord of one animal with clinical neurologic signs. Four kangaroos had antemortem retinal detachment, a potential sequel of hypertension in humans and domestic mammals. The cause of these vascular lesions in this mob is uncertain. Lesions were not associated with an infectious disease process, age, underlying renal disease, or thyroid abnormalities. In the absence of other causes, hypertension was a differential. Further investigation into clinical significance and predisposing factors, such as genetics and diet, is warranted.

Comparison of a step-down dose of once-daily ciclesonide with a continued dose of twice-daily fluticasone propionate in maintaining control of asthma.

OBJECTIVE: To compare a step-down approach in well-controlled asthma patients, as recommended by treatment guidelines, from fluticasone propionate 250 microg twice daily (FP250 BID), or equivalent, to ciclesonide 160 microg once daily (CIC160 OD) with continued FP250 BID treatment. RESEARCH DESIGN AND METHODS: Patients with well-controlled asthma prior to study entry were included in two identical, randomized, double-blind, double-dummy, parallel-group studies. After a 2-week run-in period with FP250 BID, patients were randomized to CIC160 OD (n = 58) or FP250 BID (n = 53) for 12 weeks. Primary endpoints were percentage of days with asthma control, asthma symptom-free days, rescue medication-free days and nocturnal awakening-free days. Secondary endpoints included lung function variables, asthma symptom scores, rescue medication use and asthma exacerbations. Safety variables were also recorded. RESULTS: Patients had >or= 97% of days with asthma control, 98% asthma symptom-free days and 100% of days free from rescue medication use and nocturnal awakenings in both treatment groups (median values). There were no significant between-treatment differences for any of the primary or secondary efficacy variables. Overall, 42 treatment-emergent adverse events (TEAEs) were reported in the CIC160 OD group and 49 TEAEs were reported in the FP250 BID group. There were no clinically relevant changes from baseline in the safety variables in either treatment group. CONCLUSIONS: Patients well controlled on FP250 BID, or equivalent, who were stepped down to CIC160 OD, maintained similar asthma control compared with patients who received continued treatment standardized to FP250 BID.

Attentional deficits in concussion.

PRIMARY OBJECTIVE: The purpose of the present study was to examine deficits in the alerting, orienting and executive components of attention in individuals who have recently suffered a concussion. RESEARCH DESIGN: A group design was used in which the performance by individuals with concussion was compared to control subjects matched for age, height, weight and activity level. METHODS AND PROCEDURES: Participants completed the Attentional Network Test (ANT) that breaks down attention into alerting, orienting and executive components. Reaction time and response accuracy were the dependent variables. MAIN OUTCOMES AND RESULTS: It was found that only the orienting and executive components of attention were affected by concussion, whereas the alerting component was normal. Furthermore, participants with concussion required a significantly longer time than controls to initiate correct responses. CONCLUSIONS: These results suggest that the orienting and executive components of attention are most susceptible to the effects of concussion.

An investigation of the tylosis with oesophageal cancer (TOC) locus in Iranian patients with oesophageal squamous cell carcinoma.

Oesophageal cancer is one of the ten leading causes of cancer mortality worldwide. Earlier loss of heterozygosity (or allelic imbalance) studies have implicated regions on chromosomes 3p, 5q, 9p, 13q, 17p, 17q, and 18q in the development of sporadic oesophageal cancer and recent data have linked the familial tylosis with oesophageal cancer (TOC) gene-containing region on chromosome 17q25 with this cancer. We have studied allelic imbalance (AI) at microsatellite markers both closely linked to and distant from the TOC gene locus in 60 sporadic squamous cell oesophageal cancers from Iran and have investigated the most likely candidate gene by mutation analysis in these tumours. Forty-four out of these 60 samples (73%) show allelic imbalance at one or more loci within or adjacent to the TOC minimal region, while the highest incidence of AI was observed at the D17S2244 and D17S2246 loci (almost 70% AI in informative cases), correlating with the TOC minimal region. Analysis of the coding regions of a candidate gene in these tumours failed to show an equivalently high incidence of mutation, although two mutations and one polymorphism were observed. These data support and extend previous observations that the TOC region of chromosome 17q25 may be involved in the aetiology of the sporadic form of oesophageal cancer from a number of different geographical populations and suggest that the causative gene may be epigenetically silenced rather than mutated.

Diagnosis and management of a patent urachus in a white rhinoceros calf (Ceratotherium simum simum).

A 10-day-old female southern white rhinoceros calf (Ceratotherium simum simum) was diagnosed with a patent urachus after urine was observed dribbling from the umbilicus. After being separated from its mother, the animal was sedated with i.m. butorphanol and anesthetized with isoflurane in oxygen for surgical correction of the patent urachus. Mild postoperative complications involved seroma formation and partial skin incision dehiscence, which necessitated three follow-up immobilizations for reevaluation and treatment of the surgical site. Histopathology did not reveal an infectious etiology as the cause for the complications or for the patent urachus. The etiology of the patent urachus in this animal remains undetermined. This report represents the first documented case of a patent urachus in a white rhinoceros.

Workforce planning. Careering down a radical path.

A review of the workings of the medical unit in a district general hospital concluded a radical change in roles would be needed over the next 10 years. The role of healthcare assistants, nursing and therapy assistants and auxiliaries will need to be enhanced to take on more of the unit's work in future. The review proposed the creation of a healthcare practitioner role, covering much of the current workload of junior doctors, nurses and therapists and extended responsibilities for diagnostic tests and their interpretation.

Tyzzer's disease in a red panda (Ailurus fulgens fulgens).

A debilitated 9-yr-old female red panda (Ailurus fulgens fulgens) with a recent history of corticosteroid administration displayed anorexia, depression, and diarrhea for 2 days. Blood work revealed a moderate nonregenerative anemia, leukocytosis, hypokalemia, hyperbilirubinemia, and mildly elevated alanine aminotransferase and aspartate aminotransferase. Serology was negative for occult heartworm, Toxoplasma gondii, feline leukemia virus, feline infectious peritonitis, feline immunodeficiency virus, and canine distemper virus. Electron microscopy of the feces demonstrated corona-like virus particles. The panda died 3 days after initial presentation. Histologic findings included multifocal, acute, hepatic necrosis and diffuse, necrotizing colitis. Liver and colon lesions contained intracellular, curved, spore-forming, gram-negative, silver-positive rods morphologically consistent with Clostridium piliforme. This panda most likely contracted Tyzzer's disease subsequent to having a compromised immune system after corticosteroid administration and concurrent disease.

Cardiopulmonary and anesthetic effects of medetomidine-ketamine-butorphanol and antagonism with atipamezole in servals (Felis serval).

Seven (three male and four female) 4-7-yr old captive servals (Felis serval) weighing 13.7 +/- 2.3 kg were used to evaluate the cardiopulmonary and anesthetic effects of combined intramuscular injections of medetomidine (47.4 +/- 10.3 microg/kg), ketamine (1.0 +/- 0.2 mg/kg), and butorphanol (0.2 +/- 0.03 mg/kg). Inductions were smooth and rapid (11.7 +/- 4.3 min) and resulted in good muscle relaxation. Significant decreases in heart rate (85 +/- 12 beats/min) at 10 min after injection and respiratory rate (27 +/- 10 breaths/min) at 5 min after injection continued throughout the immobilization period. Rectal temperature and arterial blood pressure did not change significantly. The PaO2 decreased significantly, and PaCO2 increased significantly during immobilization but remained within clinically acceptable limits. Hypoxemia (PaO2 < 60 mm Hg) was not noted, and arterial blood oxygen saturation (SaO2) was greater than 90% at all times. Relative arterial oxygen saturation (SpO2) values, indicated by pulse oximetry, were lower than SaO2 values. All animals could be safely handled while sedated. Administration of atipamezole (236.8 +/- 51.2 microg/kg half i.v. and half s.c.), an alpha2 antagonist, resulted in rapid (4.1 +/- 3 min to standing) and smooth recoveries.

Abdominal assessment in the home: from A to Zzz.

Conducting a through abdominal assessment in the home setting is an important part of the home care nurse's role. By using every letter of the alphabet, the tool presented in this article helps the nurse conduct a thorough health history in a concise manner. In addition, reviewing the procedure outlined in the article and using the documentation form presented, the nurse can conduct a through abdominal assessment in the home in a cost-effective manner.

Double-Blind Comparison of Apolipoprotein and Lipoprotein Particle Lowering Effects of Atorvastatin and Pravastatin Monotherapy in Patients With Primary Hypercholesterolemia.

METHODS AND RESULTS: A total of 305 subjects with primary hypercholesterolemia were randomized in a 3:1 ratio to receive either atorvastatin 10 mg daily or pravastatin 20 mg daily according to a 16-week double-blind comparative study of the effect on apolipoprotein and lipoprotein particle levels. All patients had low-density lipoprotein (LDL)-cholesterol levels between 4.2 and 6.6 mM and triglyceride concentrations below 4.5 mM at baseline. After 16 weeks of treatment, apoB (-27% and -16%; P <.001), apoE (-13.3% and -5.6%; P <.05) and the triglyceride-rich LpC-III:B particle (-33% and -26%; P <.05) levels were reduced to a significantly greater extent in the atorvastatin than in the pravastatin treatment group. Both atorvastatin and pravastatin increased apoA-I levels, an effect that was more pronounced in the pravastatin group (+7% and +11%; P <.002). The increased apoA-I levels predominated on LpA-I in the atorvastatin group (+11%) and on LpA-I:A-II in the pravastatin group (+13%). ApoA-II levels were decreased with atorvastatin to a greater extent than with pravastatin (-1% and +2.8%; P <.05). CONCLUSIONS: Although atorvastatin and pravastatin belong to the same therapeutic family, they produce different effects in apoliprotein concentrations in hypercholesterolemic patients. Atorvastatin, an agent of the new generation, appears to efficiently reduce apoB-containing lipoprotein particles containing apoC-III.

Efficacy and safety of atorvastatin compared to pravastatin in patients with hypercholesterolemia.

Plasma cholesterol and other lipoproteins play a significant role in the development of atherosclerosis and subsequent coronary heart disease (CHD). This 1 year study was designed to confirm the efficacy and safety of atorvastatin (Lipitor) compared to pravastatin, a marketed agent for low density lipoprotein cholesterol (LDL-C) reduction in hypercholesterolemic patients. Patients were recruited at 26 centers in six European countries. After a 6 week placebo baseline phase, patients were randomized to receive atorvastatin 10 mg or pravastatin 20 mg daily. The dose could be doubled at week 16, if LDL-C levels remained > or = 3.4 mmol/l (135 mg/dl). Atorvastatin significantly lowered LDL-C from baseline by 35% compared with 23% for pravastatin (P < 0.05). A total of 72% of atorvastatin patients attained the LDL-C target level of < 3.4 mmol/l, compared to 26% of pravastatin patients. Atorvastatin also significantly reduced TC, TG and apo B (P < 0.05). Safety was assessed by recording adverse events and measuring clinical laboratory parameters. The adverse event profile was similar for both treatment groups and neither treatment caused clinically relevant laboratory abnormalities. Atorvastatin 10 and 20 mg once daily is superior to pravastatin 20 and 40 mg once daily in treating patients with hypercholesterolemia.

Nisoldipine CC: clinical experience in hypertension.

Nisoldipine coat core (CC) is a long-acting formulation of the dihydropyridine calcium channel blocker nisoldipine, suitable for once-daily administration in the treatment of patients with hypertension. Data are reported from three randomized, controlled trials. In two of these, nisoldipine CC was shown to be equivalent in efficacy and tolerability to atenolol in patients with mild to moderate hypertension and to enalapril in elderly patients with hypertension. In a third study using ambulatory blood pressure monitoring in black patients with severe hypertension, nisoldipine CC maintained blood pressure control over the 24-hour dosing period. In addition, regression of left ventricular (LV) mass and improvement in LV function were observed at the end of the 4-month treatment period. Further data are presented from a pharmacokinetic pharmacodynamic modelling study investigating the potential effects of dose-dumping of nisoldipine from the controlled-release formulation, which may occur when the drug is taken with food. This study illustrates the superior control of plasma nisoldipine concentrations and blood pressure provided by the CC compared with an immediate-release formulation, and indicates that an interaction between nisoldipine CC and food is unlikely to cause adverse events. The results of these trials provide further support for the use of nisoldipine CC as an effective agent for the treatment of patients with hypertension, providing consistent antihypertensive efficacy and good tolerability with once-daily administration.

Assessing general practitioners' care of adult patients with learning disability: case-control study.

OBJECTIVE: To compare general practitioners' care of adult patients with learning disability with that of control patients in the same practice. DESIGN: Case-control study of patients and controls by a structured interview study of general practitioners. SETTING: Avon. PATIENTS: 78 adult patients with learning disability and 78 age and sex matched controls--cared for by 62 general practitioners. MAIN MEASURES: Number and content of consultations and opinions of the general practitioners. RESULTS: There were more consultations for diseases of the central nervous system and of the skin among the patients than the controls (15 v 3 for central nervous system disease and 15 v 4 skin disease). There were also significantly fewer recordings of blood pressure and cervical cytology tests (34 v 51 for blood pressure and 2 v 18 for cytology). Although more patients were taking drugs affecting the central nervous system (33 v 6), more controls were taking drugs for musculoskeletal complaints (17 v 7). CONCLUSION: Although adult patients with learning disability consult with their general practitioners at equivalent rates to other patients, they get less preventive care and consult for different types of problems than do other patients. The reasons for these differences in preventive care are not clear. Carers and general practitioners should be informed of these differences to ensure that appropriate care is given.

Eficacia e tolerabilidade da felodipina em dose unica diaria e nifedipina, duas vezes ao dia, como monoterapia na hipertensao arterial leve / Effectiveness and tolerability of felodipine once daily and nifedipine twice daily as monotherapies for mild hypertension

Esse estudo foi projetado para comparar a felodipina de liberacao prolongada com a nifedipina retard em termos de seu efeito anti-hipertensivo,telerabilidade e impacto na qualidade de vida.Setenta e sete pacientes com hipertensao arterial primaria e pressao diastolica de 95-110 mmHg,na posicao supina,foram randomizados para quatro semanas de tratamento duplo-cego com felodipina,na dose de 5mg,uma vez por dia,ou nifedipina,na dose de 20mg,duas vezes por dia.A pressao arterial foi medida no termino do intervalo posologico,isto e,24 e 12 horas depois da administracao da felodipina e nifedipina,respectivamente.Foram registrados os efeitos adversos relatados espontaneamente ou em resposta a uma pergunta aberta e a qualidade de vida foi avaliada,usando-se dois questionarios auto-administrados.Depois de quatro semans de tratamento a pressao arterial media,na posicao supina,diminuiu de 165/104 mmHg para 154/91mmHg no grupo tratado com a felodipina e de 169/102mmHg para 155/90mmHg no grupo tratado com a nifedipina.Nao huve diferencas sisgnificativas na reducao da pressao arterial na posicao supina ou em pe entre os grupos.A qualidade de vida pareceu ser semelhante entreos tratamentos,mas foram relatadoa mais reacoes adversas,em particular,edema maleolar e rubor,com a nifedipinado que com a felodipina.As reacoes adversas exigiam a interrupcao do tratamanto em 5 de 40 pacientes do grupo da nifedipina,em comparacao com 1 de 37 pacientes do grupo da felodipina.Em conclusao,a felodipina na dose de 5mg,uma vez por dia,e anifedipina,na dose de 20mg,duas vezes por dia foram igualmente eficazes como tratamento anti-hipertensivo,mas a felodipina foi melhor tolerada