Impact of two types of complete pelleted, wild ungulate feeds and two pelleted feed to hay ratios on the development of urolithogenic compounds in meat goats as a model for giraffes.

Urolith formation has been documented in giraffes and goats. As research in giraffes poses logistical challenges, 16 buck goats were used as a model. The impact of two commercially available, pelleted feeds used for giraffes, ADF-16 and Wild Herbivore (WH), as well as the impact of alfalfa hay and pellet proportions (20% hay:80% pellets, 80P or 80% hay:20% pellet, 20P) on the formation of urolithogenic precursors in goat urine was accomplished in a 2 × 2 factorial balance study. Complete diets contained 0.60, 0.32, 0.35 and 0.26% phosphorus (P) with calcium:P ratios of 1.60, 4.16, 3.06 and 5.23, for 80P-ADF-16, 20P-ADF-16, 80P-WH and 20P-WH respectively. Total faeces and urine were collected over two 5-day periods to assess N and mineral balance. Fresh urine samples were collected and evaluated microscopically for urolithic crystal content. Urinary nitrogen (N) was lower and N retention was higher in goats fed 80P diets (p < 0.05). Intake of P was greatest for goats fed 80P-ADF-16; however, urinary P excretion and P retention were not affected by treatment. Crystal scores were higher in animals receiving 80P diets (p = 0.08), with crystals being composed predominantly of calcium phosphate. Urine pH was alkaline (>8) for all treatments. Urinary P concentration, a risk factor for urolithiasis, was highest (p ≤ 0.06) in the 80P-ADF-16 treatment (0.38 vs. 0.01, 0.02 and 0.04 mg/dl for 20P-ADF-16, 80P-WH and 20P-WH respectively), reflecting its highest dietary P level. Further investigation is recommended to determine the long-term effects of these diets on urolithogenic compound formation.

Pretreatment haematological laboratory values predict for excessive myelosuppression in patients receiving adjuvant FEC chemotherapy for breast cancer.

BACKGROUND: A predictive model that identifies patients at risk of excessive neutropenia following chemotherapy would be valuable in guiding the use of supportive therapies. PATIENTS AND METHODS: We conducted a retrospective analysis of 741 patients who had received adjuvant 5-fluorouracil, epirubicin, cyclophosphamide (FEC) chemotherapy for breast cancer. The cause of every schedule alteration was identified. The ability of pretreatment haematological indices to predict for excessive myelosuppression was assessed. RESULTS: Pretreatment absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) were strongly associated with the risk of neutropenic events (NEs), febrile neutropenia (FN) or receiving suboptimal chemotherapy dose intensity (DI<85%). The timing and pattern of NEs suggest that they reflect intrinsic chemosensitivity rather than cumulative toxicity and that FN results from chance infection rather than protracted myelosuppression. By combining quintiles on the basis of the rank order of ANC and ALC, we defined five groups of patients with variable risks of NE (18%-52%), DI<85% (9%-36%) and FN (4%-21%). CONCLUSIONS: Pretreatment differential white blood cell count can be used to identify patients at increased risk of significant myelosuppression with FEC chemotherapy. Patients in the highest risk group have a risk of FN>20% and would qualify for primary prophylaxis with granulocyte colony-stimulating factor support under current guidelines.

Determination of nitrogen balance in goats fed a meal produced from hydrolyzed spent hen hard tissues.

To provide an economically viable and environmentally sound method for disposing of spent laying hens, we manufactured a proteinaceous meal from the hard tissue fraction of mechanically deboned laying hens (primarily feathers, bones, and connective tissue). We hydrolyzed the hard tissue and coextruded it with soybean hulls to create a novel feather and bone meal (FBM) containing 94.2% DM, 23.1% CP, 54.5% NDF, and 7.3% fat (DM basis). We evaluated the FBM in supplements for meat goats in which it provided 0, 20, 40, or 60% of the N added to the supplement compared with a negative control supplement with no added N source. The remainder of the N was contributed by soybean meal (SBM). Supplementation of N resulted in greater DMI than the negative control (P = 0.005), and DMI changed quadratically (P = 0.11) as FBM increased in the supplement. Digestibility of DM was similar in all diets, including the negative control (P > 0.10). Fiber digestibility increased linearly as dietary inclusion of FBM increased (P = 0.04 for NDF, P = 0.05 for ADF), probably as a result of the soybean hulls in the FBM. Nitrogen digestibility declined linearly from 60.5% with 0% FBM to 55.6% with 60% FBM (P = 0.07), but N retention changed by a quadratic function as FBM replaced SBM (P = 0.06). Negative control goats had less N digestibility (P < 0.001) and N retention (P = 0.008) than N-supplemented goats. Feather and bone meal had a greater proportion of ruminally undegradable B(3) protein than SBM (23.1 vs. 0.3% of CP, respectively). Ruminal VFA and pH were unaffected by replacing SBM with FBM, but supplying no source of N in the concentrate resulted in reduced total VFA in ruminal fluid (P = 0.04). Ruminal ammonia concentration increased quadratically (P = 0.07) as FBM increased, reflecting increased intake, and it was much less in unsupplemented goats (P < 0.001). Serum urea had less variation between 0 and 4 h after feeding in goats receiving 40 or 60% of added N as FBM in comparison with those receiving only SBM or 20% FBM. Feather and bone meal promoted a more stable rumen environment, possibly because of reduced rates of protein degradation within the rumen. A palatable by-product meal for ruminants can be made from spent laying hen hard tissue, one that supports N metabolism similar to that of traditional protein sources.

Evaluation of secondary protein nutrients as a substitute for soybean meal in diets for beef steers and meat goats.

Finding appropriate disposal techniques for waste products is one of many challenges facing the poultry-processing industry. One waste generated in significant quantities is dissolved air floatation sludge, a product of wastewater treatment. Converting dissolved air floatation sludge into a dry feed product (meal) for incorporation into livestock feed appears to be a viable solution. This meal, called secondary protein nutrients (SPN), is high in protein (45% CP), fat (28% crude fat), and minerals. The protein consists of 85% B(2) and B(3) fractions, which are moderately to slowly degradable in the rumen, and therefore may potentially escape ruminal degradation and be available for digestion in the lower gastrointestinal tract. The goal of this research was to evaluate SPN as an alternative to traditional protein sources for ruminants by substituting it on an equivalent N basis for soybean meal in cattle and meat goat diets (0, 25, 50, 75, and 100% for cattle; 0, 20, and 40% for goats). When included in corn silage-based steer diets, increasing SPN resulted in linear and quadratic declines in both DMI and ADG (P < 0.001). Dry matter intake diminished with inclusion rates above 50%, and ADG were reduced after inclusion of SPN reached 25% of added N. Feed efficiency (the reciprocal of the efficiency of gain, which is represented by G:F) declined linearly (P < 0.001) with each incremental increase in SPN. Addition of up to 40% added N as SPN in goat diets caused no change in DMI, digestibility of DM or fiber, or N retention. Ruminal VFA concentrations showed little variation in either species. Increasing the proportion of SPN in the feed caused linear declines in ruminal NH(3) in steers (P < 0.001). Increasing SPN in goat diets, however, resulted in only a trend toward reductions of this parameter (P = 0.14). The decreases observed may have resulted from decreasing ruminal protein degradability or increasing fat caused by increasing the proportion of SPN in the feed. Urinary urea N as a percentage of urinary N showed significant declines in cattle, but not in goats, over the ranges of SPN offered. These results indicate that SPN can be included in diets for ruminants to supply up to 40% of supplemental N with little negative impact on animal performance.

Identification of a novel class of inhibitor of human and Escherichia coli thymidine phosphorylase by in silico screening.

Structure-based computational screening of the National Cancer Institute database of anticancer compounds identified novel non-nucleobase-derived inhibitors of human thymidine phosphorylase as candidates for lead optimization. The hierarchical in silico screening strategy predicted potentially strong low molecular weight ligands exhibiting a range of molecular scaffolds. Of the thirteen ligands assayed for activity, all displayed inhibitory activity against Escherichia coli thymidine phosphorylase. One compound, hydrazine carboxamide 2-[(1-methyl-2,5-dioxo-4-pentyl-4-imidazolidinyl)methylene], was found to inhibit E. coli thymidine phosphorylase with an IC(50) value of 20 microM and an IC(50) value of 77 microM against human thymidine phosphorylase. As this hydantoin derivative lacks the undesirable ionic sites of existing tight-binding nucleobase-derived inhibitors, such as 5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]uracil hydrochloride, it provides an opportunity for the design of potent thymidine phosphorylase inhibitors with improved pharmacokinetic properties.

Influence of cranberry juice on attachment of Escherichia coli to glass.

An extract from fresh cranberries was shown to decrease the strength of attachment of Escherichia coli to glass coverslips when incubated together for 2 h. Pre-conditioning of the surface prior to biofilm formation also significantly weakened the strength of attached cells.

Comparison of sedative effects of romifidine following intravenous, intramuscular, and sublingual administration to horses.

OBJECTIVE: To compare sedative effects of romifidine following IV, IM, or sublingual (SL) administration in horses. ANIMALS: 30 horses that required sedation for routine tooth rasping. PROCEDURE: Horses (n = 10/group) were given romifidine (120 microg/kg) IV, IM, or SL. Heart rate, respiratory rate, head height, distance between the ear tips, thickness of the upper lip, response to auditory stimulation, response to tactile stimulation, and degree of ataxia were recorded every 15 minutes for 180 minutes. Tooth rasping was performed 60 minutes after administration of romifidine, and overall adequacy of sedation was assessed. RESULTS: IV and IM administration of romifidine induced significant sedation, but SL administration did not induce significant sedative effects. Scores for overall adequacy of sedation after IV and IM sedation were not significantly different from each other but were significantly different from scores for horses given romifidine SL. Sedative and other effects varied among groups during the first 60 minutes after drug administration; thereafter, effects of IV and IM administration were similar. CONCLUSIONS AND CLINICAL RELEVANCE: Onset of action was fastest and degree of sedation was greater after IV, compared with IM, administration of romifidine, but duration of action was longer after IM administration. Sublingual administration did not result in clinically important sedative effects.

Differential effect of the loop diuretic furosemide on short latency auditory and vestibular-evoked potentials.

OBJECTIVE: This study aimed to investigate the differential effect of the loop diuretic furosemide on the auditory and vestibular (otolith) end organs in the same animals simultaneously. DESIGN AND METHODS: Auditory nerve-brain stem-evoked responses (ABR-generated in the cochlea) and short latency vestibular-evoked responses to linear acceleration impulses (L-VsEP-generated in the otolith organs) were recorded from albino Sabra rats both before and at minute intervals after intravenous injections of the loop diuretic furosemide. In some animals, an equal volume of saline was injected to control for the effect of the injection itself. In most animals, more than one injection of saline or furosemide was possible (furosemide, N = 17 injections in 10 rats; saline, N = 18 injections in 9 rats). Peak-to-peak amplitude and peak latency changes in the first wave in each recording (representing end-organ activity) as a function of postinjection time were compared between the two evoked potentials using analysis of variance and repeated t-tests. RESULTS: Saline injections caused only minor changes in the amplitude of the ABR and the L-VsEP. After administration of furosemide, the amplitude of the L-VsEP hardly changed. However, there was a noticeable decrease in the amplitude of the ABR. CONCLUSIONS: Although furosemide has a major depressant effect on cochlear function, vestibular end-organ activity is hardly altered.

Tea tree oil allergy: what is the offending agent? Report of three cases of tea tree oil allergy and review of the literature.

Tea tree oil is currently enjoying popularity as a 'cure-all' for a variety of skin conditions, from infections to psoriasis, and many household and personal products containing Melaleuca oil are available. However, despite its chemical complexities and enthusiastic use, there have been only a few reports of allergic reactions to tea tree oil. At the Skin and Cancer Foundation (Sydney, NSW, Australia), three of 28 normal volunteers tested strongly positive to patch testing with tea tree oil. Following further patch testing with tea tree oil constituents, all three patients reacted strongly to two preparations containing sesquiterpenoid fractions of the oil. Because patients often neglect to mention that they have used 'natural' remedies, it is important that physicians are aware of the potential adverse effects of these products. Furthermore, identification of the allergenic ingredients in tea tree oil may assist the growing industry to produce safer products.

Complexity and human health: the case for a transdisciplinary paradigm.

Transdisciplinary thinking is an emerging philosophy underpinning health social science. We advance a definition of transdisciplinary thinking and link it with complexity theory. Complexity theory's concern with non-linear relationships, interactive causality and emergent properties of systems compels researchers to adopt a transdisciplinary perspective. We construct a generic framework for analyzing health processes from diverse disciplines and apply it to coronary heart disease in the Australian Coalfields. Insights from this analysis support our argument that transdisciplinary thinking maximizes understanding of the complexity of human health.

Transient evoked otoacoustic emissions in newborns in the first 48 hours after birth.

Newborns are often discharged from hospital at the age of about 48 hours. At this age, transient evoked otoacoustic emissions (TEOAEs) are not necessarily recordable in all healthy newborns. In order to determine the factors which would enable the successful recording of TEOAEs before discharge to facilitate screening for hearing, 65 fullterm newborns under 48 hours of age were tested, the youngest being 10 hours old. The ears of those neonates in whom TEOAEs could not be obtained (N = 7 neonates bilaterally, 6 unilaterally) were examined otoscopically, cleaned of vernix and retested for TEOAEs. We were thus able to record in at least one ear in all neonates tested, if the ears were clean, if they were asleep and if the testing room was quiet.

Thyroxine affects physiological and morphological development of the ear.

The onset and development of distortion product otoacoustic emissions (DPE) representing cochlear amplifier activity were studied in neonatal hyperthyroid (n = 10) and control (n = 10) rat pups. These were compared to the onset and development of auditory nerve-brainstem evoked responses (ABR) representing overall cochlear function, and to morphological development of the ear. DPEs were recorded at an earlier postnatal age to high (8 kHz) frequencies and progressed to lower (3 kHz) frequencies with age. ABRs to high-intensity clicks were recorded at least 2 days before DPEs, although DPE onset at 8 kHz preceded adult-like ABR thresholds. Both ABR and DPEs appeared earlier in the hyperthyroid rats. Histological evidence showed earlier morphological development of the ear in these animals. ABR thresholds and DPE amplitudes matured at a slower rate in the experimental group despite their earlier onset. There was no difference in ABR and DPE thresholds between adult hyperthyroid and control rats. However, in the experimental group, DPEs had smaller amplitudes to high (70 dB SPL) and to low (50 dB SPL) stimulus intensities at low frequencies. Hence, despite thyroxine-injected rat pups having earlier onset of auditory structure and function (lower ABR thresholds and earlier functioning active cochlear amplifier), it appeared that neonatal hyperthyroidism affected the later state of the cochlea, such that DPEs, especially to low-frequency stimuli, were depressed during and after maturation.

Is metabolism an important arbiter of anticancer activity of ether lipids? Metabolism of SRI 62-834 and hexadecylphosphocholine by [31P]-NMR spectroscopy and comparison of their cytotoxicities with those of their metabolites.

Antineoplastic ether lipids have entered phase I clinical trial and, although their mechanism of action remains unclear, it is widely believed that the plasma membrane is the primary cellular drug target. In the present study the hypothesis was tested that metabolism of ether lipids acts as a detoxification process. [31P]-nuclear magnetic resonance (NMR) spectroscopy was used to study the metabolism of the ether lipid SRI 62-834 (SRI) and the phosphate ester hexadecylphosphocholine (HPC) in the presence of both isolated phospholipases C and D and post-mitochondrial rat liver homogenate. Both SRI and HPC were slowly metabolised by phospholipase D to their alkyl phosphates and choline, and the alkyl phosphates were subsequently metabolised by phosphatase to yield the alcohols and inorganic phosphate. These studies failed to detect any metabolism of either SRI or HPC by phospholipase C, and the metabolism of platelet-activating factor (PAF) by this enzyme was not inhibited by the addition of either compound. The cytotoxicity of SRI, the related compound HPC and their metabolites was determined in vitro using three cell lines. Cytotoxicity was measured by analysis of cell growth kinetics, MTT assay and lactate dehydrogenase release. Closely similar results were obtained in the JB1 rat hepatoma cell line, in the non-transformed BL8 rat hepatocyte cell line, and in A549 human lung adenocarcinoma cells. SRI was the most toxic of the compounds analysed, the concentration required to produce 50% toxicity or growth inhibition (IC50) being 6-9 microM. The putative metabolite of SRI, 2,2'-bis(hydroxymethyl)tetrahydrofuran, and the known metabolites [2'-(octadecyloxymethyl)tetrahydrofuran-2'-yl]methyl phosphate and 2-hydroxymethyl-2-octadecyloxymethyltetrahydrofuran exhibited IC50 values of > 200, > 100 and 40-70 microM, respectively, consistent with metabolic detoxification. HPC was more cytotoxic (IC50, 37 microM) than its phosphate metabolite (IC50, 140 microM), but its toxicity was similar to that of its metabolite hexadecanol (IC50, 28 microM), suggesting that only the former metabolic route leads to detoxification.

Management of anterior and posterior epistaxis.

Management of epistaxis is directly related to the site of the bleeding. Anterior nosebleeds are the least dangerous and the most common, especially among children. Sinus disease, colds, allergies, abrupt temperature changes and dry heat produce fragile and hyperemic nasal mucosa that bleeds easily with nose blowing or mild abrasion. Anterior epistaxis can be reached easily and stopped by pinching the nostrils, applying silver nitrate cautery or lightly packing the anterior nose. Posterior epistaxis may be severe and may be more difficult to locate and control. Occurring more often in the elderly, posterior nosebleeds are frequently associated with hypertension, atherosclerosis and conditions that decrease platelets and clotting function. Visualization of the bleeding site is enhanced by proper positioning of the patient, use of topical vasoconstricting anesthesia and suctioning. Anterior and posterior nasal packing, hospitalization, antibiotics and close follow-up may be required to control posterior nosebleeds.

The effect of stimulus repetition rate on the diagnostic efficacy of the auditory nerve-brain-stem evoked response.

This study investigates the hypothesis that an increase in the click presentation rate during diagnostic testing with the auditory nerve-brain-stem response (ABR) will increase the efficiency with which lesions may be detected in the nervous system. Cats were exposed to conditions of hypoxia, hypercapnia and acidemia, and hypoglycemia was induced in rats. ABR was recorded using the standard 10/sec click rate and also a higher (55/sec) rate during both the control state and experimental state. Various parameters of the ABR were compared at the two click rates in the control and experimental states to see if the higher click rate was more effective in detecting pathology in the nervous system. It was found that in only a very few cases was the higher stimulus presentation rate more effective, and that in general ABR recordings at one stimulus rate only is quite sufficient for work in a clinical setting.

Desmopressin, but not vasopressin, decreases activity of the hypothalamo-neurohypophysial system in Brattleboro rats.

The pituitary neural lobe of homozygous Brattleboro rats has high rates of glucose utilization not affected by chronic treatment with exogenous vasopressin, despite attenuation of polydipsia and polyuria. We evaluated whether this effect may result from the inability of vasopressin to affect the hypothalamo-neurohypophysial metabolism or from the development of resistance to chronic vasopressin treatment. We used the [14C]deoxyglucose method to compare 28-h effects of vasopressin treatment (5 U/kg, i.m., twice a day) with that of desmopressin (100 micrograms/kg, i.p., once a day), a long-lasting antidiuretic hormone, on glucose utilization of the hypothalamo-neurohypophysial system and related structures in conscious homozygous Brattleboro rats. Vasopressin and desmopressin reduced water intake, plasma osmolality and plasma Na+ concentration similarly. Vasopressin decreased glucose utilization in the supraoptic nucleus, subfornical organ and median preoptic nucleus, but did not alter activity in the paraventricular nucleus and neural lobe. Desmopressin decreased glucose utilization in all these structures. The results indicate that desmopressin has a more potent inhibitory action on the hypothalamo-neurohypophysial system than vasopressin over this short duration of treatment. The lack of response in the neural lobe from chronic treatment with vasopressin seems to be due to its inability to affect the paraventricular nucleus metabolism. The maintenance of metabolic activity in the paraventricular nucleus of vasopressin-treated Brattleboro rats suggests that this structure contributes importantly to the metabolism of neural lobe.

The influence of sound stimulus parameters on the acoustic reflex waveform.

The transient increase in admittance seen at the beginning of the acoustic reflex response in man was investigated with a view to reaching a better understanding of its possible mechanisms. The sound stimulus intensity, its duration and its off-time were varied to investigate their effects on the morphology of the admittance waveform. The results found suggest that the transient increase may not be due to a temporary partial decoupling of the ossicular chain during the initial stages of stapedial contraction, but rather that it may be caused by a slight improvement in the coupling between the middle ear components.

EEG mean frequencies are sensitive indices of phenylalanine effects on normal brain.

We previously reported that changes in plasma phenylalanine (PHE) concentrations of 1000 microM or more adversely affected cognitive function and reduced mean frequency of the EEG power spectrum. In the present study, we characterized EEG effects of changes in plasma PHE from physiological to supraphysiological concentrations. Subjects were mentally normal children and adult volunteers with 3 different genotypes for phenylalanine hydroxylase (PHY): homozygous deficient, heterozygous, and homozygous normal. Double-blinded crossover studies were performed at equilibrium during PHE restriction and supplementation. The mean frequency of the power spectrum and the mean across a set of alpha-theta factors showed highly significant, reversible, generalized EEG slowing during PHE supplementation in subjects homozygous for PHY deficiency. Smaller but significant changes in EEG mean frequencies occurred in the heterozygous and normal subjects. Spectral profiles of EEG change were similar in both groups; the mean alpha-theta was more sensitive in the second group. Demonstration of EEG changes with PHE supplementation in normal individuals has important dietary implications.

Phosphonate biosynthesis: isolation of the enzyme responsible for the formation of a carbon-phosphorus bond.

The first isolation of a naturally occurring phosphonate in 1959 led rapidly to the discovery of a variety of metabolites containing a phosphorus-carbon bond. Phosphonates have been found in bacteria, fungi, and higher organisms such as the snail schistosome vector Biomphalaria. The biosynthetic path to the P-C bond has, however, remained undefined. Thus although it was shown twenty years ago that the isotope label from [14C]glucose or from [32P]phosphoenolpyruvate is incorporated into 2-aminoethylphosphonate by the protozoan Tetrahymena pyriformis, the presumed stoichiometric transformation of phosphoenolpyruvate to phosphonopyruvate has never been demonstrated. Low conversions of phosphoenolpyruvate into 2-aminoethylphosphonate and the trapping of phosphonopyruvate from phosphoenolpyruvate have been reported, but these reactions have not proved reproducible, and the existence of the critical enzyme, phosphoenolpyruvate phosphonomutase, has remained notional. We now report experiments that resolve this enigma, and describe the isolation and characterization of the pure mutase from T. pyriformis.

Substituted 5H-dibenz[b,g]-1,4-oxazocines and related amino acids with antiinflammatory activity.

During an investigation of the antiinflammatory properties of a number of tetracyclic derivatives of 6,8-dichlorodibenz[b,f]oxepin-10(11H)-one, the ring-expanded 1,3-dichloro-5H-dibenz[b,g]-1,4-oxazocine (9) was prepared and found to be considerable pharmacological interest. It was subsequently found that the corresponding ring-opened amino acid 66, a close analogue of the antiinflammatory agent fenclofenac, also possessed significant antiinflammatory activity, superior both to the dibenzoxazocine and to fenclofenac. These findings prompted extensive synthetic programs in both areas, and a number of derivatives in the amino acid series showed potencies considerably in excess of the standard compound. These phenylacetic acids, however, were significantly more ulcerogenic than fenclofenac whereas the corresponding dibenzoxazocines showed few signs of ulcerogenicity at doses up to 1 g/kg.