Dosing obese cats based on body weight spuriously affects some measures of glucose tolerance.

The primary objective was to investigate whether dosing glucose by body weight results in spurious effects on measures of glucose tolerance in obese cats because volume of distribution does not increase linearly with body weight. Healthy research cats (n = 16; 6 castrated males, 10 spayed females) were used. A retrospective study was performed using glucose concentration data from glucose tolerance and insulin sensitivity tests before and after cats were fed ad libitum for 9 to 12 mo to promote weight gain. The higher dose of glucose (0.5 vs 0.3 g/kg body weight) in the glucose tolerance tests increased 2-min glucose concentrations (P < 0.001), and there was a positive correlation between 2-min and 2-h glucose (r = 0.65, P = 0.006). Two-min (P = 0.016 and 0.019, respectively), and 2-h (P = 0.057 and 0.003, respectively) glucose concentrations, and glucose half-life (T1/2; P = 0.034 and <0.001 respectively) were positively associated with body weight and body condition score. Glucose dose should be decreased by 0.05 g for every kg above ideal body weight. Alternatively, for every unit of body condition score above 5 on a 9-point scale, observed 2-h glucose concentration should be adjusted down by 0.1 mmol/L. Dosing glucose based on body weight spuriously increases glucose concentrations at 2 h in obese cats and could lead to cats being incorrectly classified as having impaired glucose tolerance. This has important implications for clinical studies assessing the effect of interventions on glucose tolerance when lean and obese cats are compared.

Streptomyces sanglieri which colonised and enhanced the growth of Elaeis guineensis Jacq. seedlings was antagonistic to Ganoderma boninense in in vitro studies.

Actinomycete strain AUM 00500 was 99.5 % similar to Streptomyces sanglieri NBRC 100784(T) and was evaluated for antagonistic activity towards Ganoderma boninense, the causative fungus of basal stem rot of oil palm. The strain showed strong antifungal activity towards G. boninense in in vitro and SEM analysis showed various modes of inhibition of the fungus. Ethyl acetate extracts of single culture and inhibition zone of cross-plug culture by HPLC indicated that strain AUM 00500 produced two different antibiotics of the glutarimide group namely cycloheximide and actiphenol. In greenhouse trials, oil palm seed treated with spores of S. sanglieri strain AUM 00500 at 10(9) cfu/ml showed significant (P < 0.05) increase in oil palm seedlings growth when compared to the control. Streptomyces sanglieri strain AUM 00500 successfully colonised the epidermal surface of the roots of treated oil palm seedlings and it was recovered from root fragments plated on starch casein agar.

Ultrasonography alone for diagnosis of breast cancer in women under 40.

INTRODUCTION: Recent guidelines suggest that ultrasonography should be used as the primary imaging modality in women under 40 years of age with mammography being offered if further imaging is required. The aim of this study was to assess the adequacy of ultrasonography and the utility of mammography in this patient group by reviewing the role these imaging techniques had in the diagnosis of breast cancer in our unit. METHODS: All breast cancers diagnosed in patients 39 years or younger from June 2009 to June 2011 were reviewed. This was a retrospective review of presentation, clinical findings, imaging modality (ultrasonography, mammography, magnetic resonance imaging [MRI]) and histology. Mammography was the primary imaging modality until May 2011 in women between 35 and 39 years of age. Both invasive and intraductal carcinoma were included in the study but lobular carcinoma in situ was excluded. RESULTS: A total of 2,495 patients were referred to the symptomatic breast clinic in this age group during the study period. Thirty women were identified with either invasive cancer (n=27) or ductal carcinoma in situ (n=3). Twenty-eight patients underwent mammography, graded as uncertain, suspicious or malignant in the majority. Malignancy was missed in one patient. All 30 patients underwent ultrasonography, reported as uncertain, suspicious or malignant, an indication for diagnostic core biopsy. Ultrasonography alone did not miss any cancers but did fail to detect multifocal disease in one patient. CONCLUSIONS: In this study group, ultrasonography was reliable as the primary imaging modality for women under 40, identifying all cancers in this cohort. Mammography and/or MRI remain essential adjuncts to accurately determine multifocality and/or the extent of disease.

Rapid identification of cyclic tetrapyrrolic photosensitisers for photodynamic therapy using on-line hyphenated LC-PDA-MS coupled with photo-cytotoxicity assay.

INTRODUCTION: Photodynamic therapy is a treatment modality that involves site-directed generation of cytotoxic reactive oxygen species by light-activated photosensitisers. OBJECTIVE: In order to rapidly identify new photosensitisers from natural extracts, we developed a liquid chromatography-photodiode array-mass spectrometry (LC-PDA-MS) method to rapidly identify plant extracts that contain photosensitisers, particularly those possessing a cyclic tetrapyrrole structure. METHOD: Six previously isolated compounds (1-6) were identified in bioactive fractions derived from 15 plant extracts on the basis of their chromatographic retention times, UV-visible profiles, accurate mass and fragmentation patterns. RESULTS: Samples containing uncommon photosensitisers were rapidly identified using this method, and subsequent scale-up isolation efforts led to two new compounds (7 and 8) which were confirmed to be active photosensitisers in a photo-cytotoxicity assay. CONCLUSION: This method serves as a useful tool in prioritising samples that may contain new photosensitisers out of a larger group of photo-cytotoxic natural products extracts.

Iron deficiency anemia and cardiac mortality in patients with left ventricular systolic dysfunction undergoing coronary stenting.

AIM: The aim of this study was to assess cardiac mortality in patients with reduced ejection fraction (EF< or =45%) and anemia (Hb< or =12 g/dL) undergoing coronary stenting and to investigate whether iron-deficiency anemia influenced outcome when compared to non-anemic patients or patients with other types of anemia. METHODS: One hundred twenty consecutive patients undergoing percutaneous coronary intervention (PCI) between April 2003 and December 2005 were identified and followed for a median of 30 months. Patients were divided into 2 groups, anemic (Hb< or =12 g/dL) and non-anemic. Anemic patients were then divided into 3 sub-groups based on laboratory analysis and anemia work-up: iron-deficiency, malignancy-associated, and anemia of chronic disease (including chronic kidney disease). Mortality rates and cause of death were retrieved using both the Social Security database and the hospital records. RESULTS: Thirty-one percent of patients had iron deficiency, 24% had a malignancy-associated anemia and 45% had anemia of chronic disease. Overall mortality was 12% of which 29% was cardiac death. All-cause and cardiac mortality were significantly higher in anemic vs. non-anemic patients, (31% vs. 6%, P<0.001, and 10% vs. 1%, P=0.016, respectively). Iron-deficiency anemia strongly predicted cardiac mortality (33% vs. 1% in non-anemic patients, P<0.001), while malignancy-associated anemia was the strongest predictor of non-cardiac death (57% vs. 4% in non-anemic patients, P<0.001). Anemia of chronic disease neither predicted cardiac nor non-cardiac death. CONCLUSIONS: To the authors' knowledge, this is the first study to show that iron-deficiency anemia is a strong predictor of cardiac death when compared to patients with other types of anemia or to non-anemic patients.

Imaging appearances and endovascular management of uncommon pseudoaneurysms.

Pseudoaneurysms are uncommon and their aetiology is varied. They occur in numerous anatomical locations and present with a multitude of clinical presentations sometimes life-threatening. This review describes the causes, sites, and presentations of uncommon pseudoaneurysms, as well as illustrating their diagnostic appearances and endovascular management.

Sugars consumption by 379 11-12-year-old English children in 1990 compared with results in 1980.

The amount of sugars consumed by young adolescents was assessed in 1990 using the same methods as those employed in a similar survey in 1980. The children were the same age (mean 11 years 6 months) and from the same seven schools in both survey. In 1980, 405 children completed the study and 379 in 1990. Information was collected using two 3-day dietary diaries, each child being interviewed by a dietitian upon completion of a diary. The dietitian in this study was calibrated closely with the dietitian who undertook the 1980 study so as to ensure comparable diet evaluation methods. Total sugars consumption was unchanged (117 g/day in 1980, 118 g/day in 1990) but consumption of non-milk extrinsic sugars increased (83 g/day in 1980, 90 g/day in 1990) and milk and intrinsic sugars decreased (34 g/day in 1980, 28 g/day in 1990) between the two surveys. In 1990, non-milk extrinsic sugars contributed 17% to total dietary energy intake, while milk and intrinsic sugars contributed 5%. There was little difference in percent contributions between the sexes, but some social-class trends were apparent. Confectionery provided 33% and soft drinks provided 27% of non-milk extrinsic sugars, these two dietary sources providing 60% of non-milk extrinsic or 46% of total sugars intake. These levels of consumption are considerably higher than those currently recommended in the UK.

Congenital disorder of glycosylation type 1a: three siblings with a mild neurological phenotype.

We report 3 siblings (1 male and 2 female) recently diagnosed with congenital disorder of glycosylation type Ia (CDG-Ia) in their mid-20s. They experience mild mental retardation but manage to function independently in society. Their professions are library assistant, professional artistic painter and secretarial work. All three siblings have cerebellar hypoplasia and ataxia, but are able to ambulate easily. Two of the siblings have required strabismus surgical repairs. All have antithrombin III deficiency, osteoporosis, and mild dysmorphic features. Hypergonadotrophic hypogonadism was a feature of the two female siblings. A type 1 sialotransferrin pattern and phosphomannomutase (PMM) deficiency have been demonstrated. They are compound heterozygotes for R141H and L32R mutations in the PMM2 gene. While there is clinical heterogeneity in CDG-Ia, we believe that our patients are among the mildest of intellectually affected CDG-Ia patients reported to date.

Seizures, ataxia, developmental delay and the general paediatrician: glucose transporter 1 deficiency syndrome.

AIM: Glucose transporter 1 deficiency syndrome (GLUT1-DS) is an important condition for the general paediatrician's differential armamentarium. We describe a case series of eight patients in order to raise awareness of this treatable neurometabolic condition. The diagnosis of GLUT1-DS is suggested by a decreased absolute cerebrospinal fluid (CSF) glucose value (<2.2 mmol/L) or lowered CSF: plasma glucose ratio (<0.4). METHODS: This is a review of eight Queensland patients with GLUT1-DS. The clinical presentation, clinical course, laboratory investigations and treatment outcomes are discussed. RESULTS: The clinical features noted in our patient cohort include combinations of ataxia, developmental delay and a severe seizure disorder that is refractory to anticonvulsant medications. Seizures are the most common clinical manifestation and may be exacerbated by phenobarbitone. The paired CSF: plasma glucose results ranged from 0.2 to 0.39 (normal <0.6) with an average of 0.33. 3-O-Methyl-D-Glucose uptake and GLUT1 Genotyping analysis have been performed on five patients thus far. Rapid and impressive seizure control was observed in 100% of our patients once the ketogenic diet was instituted, with half of the cohort being able to wean completely from anticonvulsants. CONCLUSION: Children presenting with a clinical phenotype consisting of a refractory seizure disorder, ataxia and developmental delay should prompt the consideration of Glucose transporter 1 deficiency syndrome. While the diagnostic test of lumbar puncture is an invasive manoeuvre, the diagnosis provides a viable treatment option, the ketogenic diet. GLUT1-DS displays clinical heterogeneity, but the value of early diagnosis and treatment is demonstrated by our patient cohort.

Basal plasma insulin and homeostasis model assessment (HOMA) are indicators of insulin sensitivity in cats.

The objective of this study was to compare simpler indices of insulin sensitivity with the minimal model-derived insulin sensitivity index to identify a simple and reliable alternative method for assessing insulin sensitivity in cats. In addition, we aimed to determine whether this simpler measure or measures showed consistency of association across differing body weights and glucose tolerance levels. Data from glucose tolerance and insulin sensitivity tests performed in 32 cats with varying body weights (underweight to obese), including seven cats with impaired glucose tolerance, were used to assess the relationship between Bergman's minimal model-derived insulin sensitivity index (S(I)), and various simpler measures of insulin sensitivity. The most useful overall predictors of insulin sensitivity were basal plasma insulin concentrations and the homeostasis model assessment (HOMA), which is the product of basal glucose and insulin concentrations divided by 22.5. It is concluded that measurement of plasma insulin concentrations in cats with food withheld for 24 h, in conjunction with HOMA, could be used in clinical research projects and by practicing veterinarians to screen for reduced insulin sensitivity in cats. Such cats may be at increased risk of developing impaired glucose tolerance and type 2 diabetes mellitus. Early detection of these cats would enable preventative intervention programs such as weight reduction, increased physical activity and dietary modifications to be instigated.

Transpleural ultrasound diagnosis of a pulmonary arteriovenous malformation.

Pulmonary arteriovenous malformations (PAVMs) are rare. We discuss a case of an 81-year-old female who attended hospital with a haemothorax. Ultrasound not only demonstrated an echogenic effusion in the right pleural space, but also identified an associated tubular structure. Doppler was applied to this structure, which exhibited pulsatile flow. This raised the possibility of a PAVM, which was subsequently confirmed on CT and angiography. Although, PAVM is a rare cause of haemothorax, the diagnosis should still be considered and transpleural ultrasound can detect these malformations non-invasively by the bedside.

Tolerability of topiramate in children and adolescents.

OBJECTIVE: To examine the tolerability of topiramate (TPM) in paediatric practice. METHODOLOGY: A retrospective cohort study of patients aged less than 18 years commenced on TPM by paediatric neurologists. Patients were identified from the dispensing databases of two paediatric tertiary referral hospitals and from the authority prescription records of four paediatric neurologists. The clinical data were obtained from the patients' medical records. RESULTS: There were 159 patients who were identified as having been commenced on TPM and follow-up data were available for 127 (80%) patients. The median (range) age at commencement of TPM was 8.1 (0.5-17.9) years, with 12 patients aged less than 2 years. After 4 years, 60% of patients had ceased the medication. Treatment limiting adverse effects included aggression/psychosis (n = 10), cognitive impairment/sedation (n = 6), anorexia/weight loss (n = 4) and desquamation (n = 1). Prior aggression (hazard ratio 5.91 (2.12-16.44)) and female gender (hazard ratio 2.94 (1.02-8.41)) were risk factors for ceasing TPM because of an adverse event. Thirty percent of children commenced on TPM experienced a treatment limiting adverse effect within 2 years of commencement. CONCLUSIONS: The frequency of treatment limiting adverse events in children receiving topiramate is higher than previously reported.

Cell kinetic studies in the murine ventral tongue epithelium: thymidine metabolism studies and circadian rhythm determination.

The oral mucosa is a rapidly replacing body tissue that has received relatively little attention in terms of defining its cell kinetics and cellular organization. The tissue is sensitive to the effects of cytotoxic agents, the consequence of which can be stem cell death with the subsequent development of ulcers and the symptoms of oral mucositis. There is considerable interest in designing strategies to protect oral stem cells and, hence, reduce the mucositis side-effects in cancer therapy patients. Here we present details of a new histometric approach designed to investigate the changing patterns in cellularity in the ventral tongue mucosa. This initial paper in a series of four papers presents observations on the changing patterns in the labelling index following tritiated thymidine administration, which suggest a delayed uptake of tritiated thymidine from a long-term intracellular thymidine pool, a phenomenon that will complicate cell kinetic interpretations in a variety of experimental situations. We also provide data on the changing pattern of mitotic activity through a 24-h period (circadian rhythms). Using vincristine-induced stathmokinesis, the data indicate that 54% of the basal cells divide each day and that there is a high degree of synchrony in mitotic activity with a mitotic peak occurring around 13.00 h. The mitotic circadian peak occurs 9-12 h after the circadian peak in DNA synthesis. The data presented here and in the subsequent papers could be interpreted to indicate that basal cells of BDF1 mice have an average turnover time of about 26-44 h with some cells cycling once a day and others with a 2- or 3-day cell cycle time.

Simulation of cell proliferation in mouse oral epithelium, and the action of epidermal growth factor: evidence for a high degree of synchronization of the stem cells.

Computer simulation has been carried out to help to determine the cell-proliferative mechanisms underlying data gathered from a double-labelling experiment on the dorsal tongue of the mouse. Good fits to the data have been obtained by assuming that there is a high degree of synchrony in the stem cells, which have a 24-h cell cycle time, and that daughters of these cells undergo two further divisions, with mean cell cycle times of 48 h, before differentiating. This results in one-seventh of proliferative cells being stem cells, which ties in well with the concept of epidermal proliferative units. There is no need to assume that S-phase duration changes diurnally. The administration of epidermal growth factor seems to increase the degree of synchrony. In such systems, the influx to S-phase and the efflux from it have very sudden short peaks, which it is impossible to observe unless observations are taken very frequently. There are therefore implications for the designs of experiments that attempt to study diurnal rhythms or the effect of factors that disturb the normal proliferative pattern of cells.