Direct thermo-optical tuning of silicon microresonators for the mid-infrared.

We use light from a visible laser diode to directly tune silicon-on-chip microresonators by thermo-optical effect. We show that this direct tuning is local, non invasive and has a much smaller time constant than global temperature tuning methods. Such an approach could prove to be highly effective for Kerr comb generation in microresonators pumped by quantum cascade lasers, which cannot be easily tuned to achieve comb generation and soliton-mode locked states.

Impaired Odor Perception in Autism Spectrum Disorder Is Associated with Decreased Activity in Olfactory Cortex.

Autism Spectrum Disorders (ASDs) are characterized by atypical sensory functioning in the visual, tactile, and auditory systems. Although less explored, olfactory changes have been reported in ASD patients. To explore these changes on a neural level, 18 adults with ASD and 18 healthy neurotypical controls were examined in a 2-phase study. Participants were first tested for odor threshold and odor identification. Then, (i) structural magnetic resonance (MR) images of the olfactory bulb were acquired, and (ii) a functional MR imaging olfaction study was conducted. ASD patients exhibited decreased function for odor thresholds and odor identification; this was accompanied by a relatively decreased activation in the piriform cortex. In conclusion, these findings suggest, that the known alterations in olfaction in ASD are rooted in the primary olfactory cortex.

New records of angular rough sharks Oxynotus centrina in the coastal waters of Malta, with observations on post-capture resilience and release behaviour.

One male and one female angular rough sharks Oxynotus centrina were caught south-east of Malta between May and June at a depth of 60-100 m < 5 km from shore. The immature female (total length, LT 565 mm) was landed dead but the male (535 mm LT ) was found alive. This communication presents important biological observations on post-capture recovery and release behaviour of this species.

Lymphspiration: The Axillary Web and Its Lymphatic Origin.

Axillary web syndrome (AWS) is a frequently overlooked problem that causes morbidity in the early post-operative period following cancer surgery with axillary lymph node removal (1-3). AWS, also known as "cording" was first described in 2001 by Moskovitz as "a visible web of axillary skin overlying palpable cords of tissue that are made taut by shoulder abduction" (1). Over a decade has passed since Moskovitz's seminal article was published, and we still lack a good understanding of AWS. This condition has been suboptimally studied using widely differing criteria. This has resulted in almost meaningless data such as the incidence of the problem, which varies from 6 to 72% following cancer surgery with axillary lymph node dissection (ALND) or sentinel node biopsy (SNB) (1-5). AWS continues to perplex the medical and scientific community. For instance, there is no explanation for the observation that individuals with a lower body mass index (BMI) are at higher risk for AWS (1-3). There are differing views on the physiological and etiological aspects of AWS. Some believe there is a vascular component involving the lymphatic and/or venous system (1, 6-11). Others consider the cord to be composed of fascial tissue (12). The terminology used to describe the cord varies dependent on the researcher's opinions, which are based on their speculations as to the underlying pathophysiology of the condition. The purpose of this paper is to present a new perspective that supports the theory that AWS is associated with the lymphatic system.Based on our clinical experience including more in-depth analysis of specific cases, our clinical research, and the accumulated literature, we present our proposal to explain the pathophysiology of AWS, define the period of onset and duration of AWS, outline possible reasons for the association between AWS and BMI, and postulate why we occasionally see cases of AWS that are associated with conditions that disturb normal lymphatic function but are unrelated to surgery.

Characterizing axillary web syndrome: ultrasonographic efficacy.

The aim of this study was to determine if ultrasound could successfully characterize axillary web syndrome (AWS) and clarify the pathophysiologic basis of AWS as a vascular or lymphatic abnormality, or an abnormal tissue structure. This prospective study evaluated women who developed AWS following breast cancer surgery. Using an 18 MHz ultrasound transducer, images were taken of the AWS cord and compared to mirror images on the contralateral side. A blinded radiologist assessed the ultrasound characteristics of and structural changes in the skin and subcutaneous tissue and formulated an opinion as to the side in which AWS was located. Seventeen subjects participated in the study. No structure or abnormality consistent with AWS could be identified by ultrasound. There were no statistical differences between the ipsilateral and contralateral side in skin thickness; subcutaneous reflector thickness, number or disorganization; or subcutaneous tissue echodensity (p>0.05). The radiologist correctly identified the side with AWS in 12 of 17 subjects (=0.41). A distinct ultrasonographic structure or abnormality could not be identified in subjects with AWS using 18 MHz ultrasound. The inability to identify a specific structure excludes the possibility that AWS is associated with vein thrombosis or a fascial abnormality, and supports the theory that AWS may be pathology that is not visible with 18 MHz ultrasound, such as microlymphatic stasis or binding of fibrin or other proteins in the interstitial space.

Quality of life in breast cancer survivors: An assessment of international breast cancer dragon boat racers.

Resistance exercise is deemed safe for women recovering from conventional breast cancer therapies but few clinicians are aware that dragon boat racing, as a form of resistive exercise, is available to the breast cancer community. The objectives of this study were to 1) increase clinician awareness of dragon boat racing (DBR) in breast cancer survivors as a community-based physical activity, and 2) evaluate quality of life (QOL) in breast cancer survivors with or without lymphedema who participate in DBR. This prospective, observational study surveyed 1,069 international breast cancer dragon boat racers from eight countries to compare function, activity, and participation in women with and without selfreported lymphedema using the Lymph-ICF questionnaire. Seventy-one percent of women (n=758) completed the questionnaires. Results revealed significantly higher Lymph-ICF scores in the lymphedema participants, signifying reduced QOL, when compared to the nonlymphedema participants (p<0.05), except for "go on vacation" for which no statistical difference was reported (p=0.20). International breast cancer survivors with lymphedema participating in DBR at an international competition had reduced function, limited activity, and restricted participation compared to participants without lymphedema. Clinicians should consider utilizing DBR as a community-based activity to support exercise and physical activity after a breast cancer diagnosis.

Axillary web syndrome following breast cancer surgery: symptoms, complications, and management strategies.

Axillary web syndrome (AWS) is a common condition occurring in up to 86% of patients following breast cancer surgery with ipsilateral lymphadenectomy of one or more nodes. AWS presents as a single cord or multiple thin cords in the subcutaneous tissues of the ipsilateral axilla. The cords may extend variable distances "down" the ipsilateral arm and/or chest wall. The cords frequently result in painful shoulder abduction and limited shoulder range of motion. AWS most frequently becomes symptomatic between 2 and 8 weeks postoperatively but can also develop and recur months to years after surgery. Education about and increased awareness of AWS should be promoted for patients and caregivers. Assessments for AWS should be performed on a regular basis following breast cancer surgery especially if there has been associated lymphadenectomy. Physical therapy, which consists of manual therapy, exercise, education, and other rehabilitation modalities to improve range of motion and decrease pain, is recommended in the treatment of AWS.

Fibre optic spectrophotometry for the in vitro evaluation of ultraviolet radiation (UVR) spectral transmittance of rabbit corneas.

A fibre optic spectrophotometer front-end system for measuring corneas to overcome shortcomings associated with existing instruments was tested. The system allowed prompt measurement postmortem, minimizing beam pathlength to reduce the effects of scatter and unwanted refraction and eliminated optical interfaces and cuvette media. Rabbit corneas were excised immediately postmortem and placed on a detecting fibre optic coupled to an Ocean Optics spectrophotometer and illuminated by a deuterium-halogen source. The compact instrument with its small beam size allowed tissue profiling at test points across the corneal surface and efficient interchange for comparison of different tissues. This simplified system operation allowed rapid tissue altering to study induced changes on transmittance. The corneal transmittance data showed a consistent sharp cut-off at 320 nm in the ultraviolet radiation (UVR) spectrum, which decayed rapidly from postmortem swelling. Inter- and intra-corneal consistency was demonstrated by comparing data from different regions of the same cornea and those from opposite eyes. Changes to the spectra, particularly in the UVB below 300 nm, were evident when the corneal epithelium was removed, indicating that this layer is not the only corneal UVR filter. The new system reduced much of the variability associated with previous methods, as it rapidly measured corneal transmittance postmortem. Data are in broad agreement with published transmittance curves. The removal of the corneal epithelium revealed a substantial stromal contribution to the overall corneal UVR absorption, suggesting that corneas with pathologically or iatrogenically thinned stromas are less effective UVR blockers.

Incidence of MRI-detected brain lesions and neurocognitive function after electrical cardioversion in anticoagulated patients with persistent atrial fibrillation.

BACKGROUND: After electrical cardioversion (eCV) in patients with atrial fibrillation (AF), the risk for clinically apparent cerebral thromboembolism is increased in the subsequent weeks. To date, there is little evidence on the incidence of acute brain lesions (ABL) detected with cerebral magnetic resonance imaging (MRI) after eCV, in particular in patients treated with the Non-Vitamin K Antagonist oral anticoagulants (NOAC). AIMS: The aim of this pilot study was to evaluate the incidence of MRI-detected ABL, as well as the neuro-cognitive function after eCV in patients with persistent AF using NOACs as compared to phenprocoumon. METHODS AND RESULTS: 50 consecutive patients with persistent AF (mean age 69.6±3.5years, 26 male) were evaluated in this prospective study. Cerebral 3Tesla MRI and neuro-cognitive assessment using the National Institutes of Health Stroke Scale (NIHSS) score and the Montreal Cognitive Assessment Test (MoCA) were performed in all patients within 24h before eCV and after a median follow-up duration of 14days (Q1: 13, Q3: 19days). Patients were treated with an OAC for at least 4weeks after eCV and according to the CHA2DS2-Vasc-score thereafter. Thirty-nine patients were treated with NOACs (Dabigatran 10/50 [20%], Apixaban 21/50 [42%] and Rivaroxaban 8/50 [16]) and 11/50 patients with Phenprocoumon (22%). No patient developed ABL on cerebral MRI at the 2-week follow-up. Neurological as well as cognitive function were similar before and 2weeks after eCV (NIHSS-score: p=0.35; MoCa score: p=0.21). CONCLUSION: Electrical CV in patients with persistent AF, in particular when treated with NOACs, carries a low risk for the development of MRI-detected ABL or neurocognitive decline. CLINICAL TRIALS REGISTRATION: GermanClinicalTrialsRegister number: DRKS00010460.

Altered arachidonic acid metabolism during differentiation of the human monoblastoid cell line U937.

The human cell line U937 was used as a model for differentiation along the mononuclear phagocyte lineage. Following treatment with the phorbol ester TPA, PGE2 and TxB2 secretion was induced 50-100-fold, and both PGF2 alpha and PGI2 levels became detectable in the supernatant of TPA-differentiated U937 cells. The content of the prostaglandin precursor, arachidonic acid, remained unchanged in the cellular phospholipids of undifferentiated and TPA-differentiated U937 cells. Of the enzymes involved in the availability and metabolism of arachidonic acid, phospholipase A2 activity was increased 2-fold in the membranes of TPA-differentiated U937 cells, whereas lysophosphatide acyltransferase activity remained unaltered. Cyclooxygenase activity, however, was enhanced 5-10-fold, which was due to enhanced expression of the enzyme as demonstrated by dot-blot analysis. The data suggest that the capacity to secrete prostaglandins is acquired during differentiation with TPA and results mainly from an increased cyclooxygenase activity. Despite the capacity of TPA-differentiated U937 cells to synthesize prostaglandins, none of the known monocytic stimuli further stimulated prostaglandin secretion in TPA-differentiated U937 cells. Generation of leukotrienes appears to represent a later state in the differentiation along the monocyte-macrophage lineage, since neither LTB4 nor cysteinyl-leukotrienes were detectable in the supernatants of either undifferentiated or TPA-differentiated U937 cells.

Interaction of fluorinated ether anesthetics with artificial membranes.

Fluorine-19 nuclear magnetic resonance spectroscopy is applied to the study of the environment of dipalmitoyl phosphatidylcholine-bound fluorinated ether anesthetics (enflurane, fluoroxene and methoxyflurane) both below and above the lipid gel to liquid crystal phase transition temperature. Line widths and spin-lattice relaxation time (T1) measurements are consistent with substantial immobilization of the lipid-bound anesethetic molecules. Heating anesthetic/lipid mixtures above the lipid transition temperature leads to narrowing of the lipid-bound anesthetic fluorine resonances accompanied by little or no change in anesthetic fluorine-19 chemical shifts, suggesting that although the mobility of the bound anesthetic increases at the higher temperature, the nature of the anesthetic-lipid interaction changes little as a result of this phase change. Differential scanning calorimetric studies of the effects of these anesthetics on the phase transition behavior of the phospholipid indicate that the regions of the bilayer in which volatile anesthetics partition at lower concentrations are different from the regions in which they partition at higher concentrations.

Use of total-body electrical conductivity for the assessment of body composition in middle-aged and elderly individuals.

Body composition was predicted for 114 middle-aged and elderly individuals aged 35-90 y by using total-body electrical conductivity (TOBEC), densitometry, and hydrometry. Highly significant correlations were achieved between the TOBEC Phase value and fat-free mass (FFM) determined by densitometry (FFMd) and hydrometry (FFMdw) with values ranging from 0.713 to 0.981. TOBEC predicted FFM (FFMT) was consistently higher than either FFMd or FFMdw for both men and women in all age groups. A theoretical calculation of percent body fat was performed with a three-component model with body density, total body water, and bone mineral content. The recalculation of fat was used to estimate a new FFM (FFMnew). These calculations resulted in a decrease in fat and an increase in FFMnew. Because the TOBEC signal is unaffected by bone mineralization, FFMT may provide a more accurate estimation of body composition than do FFMd or FFMdw in this group of individuals.

Glucocorticoid-induced reduction of prostanoid synthesis in TPA-differentiated U937 cells is mainly due to a reduced cyclooxygenase activity.

The molecular mechanism of the glucocorticoid-induced inhibition of prostanoid synthesis was investigated in human monoblastoid U937 tumor cells and phorbol ester (TPA)-differentiated U937 cells. Prostanoid synthesis was inhibited in TPA-differentiated U937 cells by glucocorticoids such as dexamethasone and prednisolone, whereas aldosterone and progesterone showed no inhibitory effect. None of these methods had any influence on prostanoid secretion of undifferentiated U937 cells. Receptor binding studies revealed the presence of glucocorticoid receptors in both undifferentiated and TPA-differentiated U937 cells (Kp approximately 5 x 10(-9)M), however, the number of receptors per cell was increased 10-fold in TPA-differentiated U937 cells. Expression of lipocortin I and II as measured by Western blot analysis was not affected by dexamethasone. In TPA-differentiated cells, dexamethasone decreased the activities of two enzymes essential for prostanoid synthesis, cyclooxygenase and phospholipase A2, by 60-70% and 30%, respectively. Cells pretreated with the translation inhibitor cyclohexmide and dexamethasone showed similar cyclooxygenase and phospholipase A2 activities as cells treated with cycloheximide alone. Western blot analysis demonstrated that the significantly decreased cyclooxygenase activity correlated with an inhibited protein synthesis. In this human macrophage-like model glucocorticoids thus interfere at least at two levels with prostanoid synthesis by inhibiting the activities of phospholipase A2 as well as cyclooxygenase.

The modulation of chlamydial replication by HLA-B27 depends on the cytoplasmic domain of HLA-B27.

OBJECTIVE: The intracellular persistence of viable Chlamydia trachomatis (CT) within the joint is thought to initiate and maintain the inflammatory process in CT-induced arthritis. CT-induced arthritis is associated with HLA-B27. Recently it was shown that HLA-B27, besides being a T-cell restriction element, can directly influence the invasion and/or replication of enterobacteriae and alters salmonella-induced signal transduction. It was the aim of this study to analyze the effect of HLA-B27 on CT-invasion and replication in human host cells. METHODS: Human Hela cells and Hela cells transfected with either HLA-B27 cDNA or controls (HLA-A1 cDNA; HLA-B27 mutant = HLA-B27 without cytoplasmic tail; B27Q10 = HLA-B27 Exon 1-4 linked to Exon 5 of murine Q10) were infected with CT. By direct immunofluorescence chlamydial invasion was determined 4 hours post infection (p.i.), chlamydial replication 2 days and 4 days p.i. The number of infective CT in the different cell lines was determined by titration of the cell lysates on Hep-2 cells with subsequent immunoperoxidase staining. RESULTS: Invasion was not affected by HLA-B27. However, formation of chlamydial inclusion bodies and replication was suppressed by HLA-B27. Genetically engineered mutants of HLA-B27 (HLA-B27 mutant, B27Q10) lacking the cytoplasmic tail of HLA-B27 did not affect replication. CONCLUSION: The reduction of chlamydial replication by HLA-B27 depends on the cytoplasmic domain of HLA-B27, thus providing a new hypothesis for chlamydial persistence in HLA-B27 positive reactive arthritis.

Estimation of apparent quadrupolar coupling constants for complexes of magnesium ions with mono- and dicarboxylic acid ligands. Applications to magnesium ion: protein interactions.

25Mg+2 ion NMR studies of complexes of magnesium ions with acetate and malonate ligands have yielded apparent quadrupolar coupling constants, chi, of approximately 1.5 MHz. The aquo magnesium ion yields a smaller chi value of 0.12 MHz, consistent with its expected higher symmetry. chi values for magnesium ion: acetate and magnesium ion: malonate complexes are utilized to calculate observed linewidths for magnesium ion: bovine prothrombin fragment 1 and magnesium ion: human Factor XII interactions. These calculated values are compared with observed values and implications of the agreement are discussed.

Evaluation of urinary carnitine and taurine excretion in 5 cystinuric dogs with carnitine and taurine deficiency.

Five client owned dogs with cystinuria were diagnosed with carnitine and taurine deficiency while participating in a clinical trial that used dietary management of their urolithiasis. Stored 24-hour urine samples collected from the cystinuric dogs before enrollment in the clinical diet trial were quantitatively evaluated for carnitine and taurine. These results were compared to those obtained from 18 healthy Beagles. Both groups of dogs were fed the same maintenance diet for a minimum of 2 weeks before 24-hour urine collection. The protocol used for 24-hour urine collections was the same for cystinuric dogs and healthy Beagles except that cystinuric dogs were catheterized at baseline, 8 hours, 12 hours, and at the end of the collection, whereas Beagles were catheterized at baseline, 8 hours, and at the end of the collection. Three of 5 dogs with cystinuria had increased renal excretion of carnitine. None of the cystinuric dogs had increased renal excretion of taurine, but cystinuric dogs excreted significantly less (P < .05) taurine in their urine than the healthy Beagles. Carnitinuria has not been recognized previously in either humans or dogs with cystinuria, and it may be 1 risk factor for developing carnitine deficiency. Cystinuric dogs in this study were not taurinuric; however, cystine is a precursor amino acid for taurine synthesis. Therefore, cystinuria may be 1 risk factor for developing taurine deficiency in dogs. We suggest that dogs with cystinuria be monitored for carnitine and taurine deficiency or supplemented with carnitine and taurine.

Evaluation of the morphologic characteristics and prevalence of canine urocystoliths from a regional urolith center.

OBJECTIVE: To determine whether morphology of single-mineral urocystoliths and age, sex, or breed data could be applied to facilitate radiographic and clinical urocystolith mineral type prediction, respectively, in dogs. SAMPLE POPULATION: Database of 2,041 dogs with pure mineral composition urocystoliths. PROCEDURE: All uroliths were characterized according to geologic descriptive terminology and by breed, sex, and age of dog at time of sample submission. Summary statistics were used to compare features with specific mineral types. Observed trends were analyzed for statistical relevance between observed and expected frequencies for age, sex, color, size, shape, and surface, using the null hypothesis that differences by urocystolith mineral type did not exist. On the basis of expected breed occurrence derived by equations, the null hypothesis that urocystolith occurrence paralleled canine breed popularity was tested. RESULTS: Urocystoliths > 10 mm in any dimension were > 92% likely to be magnesium ammonium phosphate hexahydrate (MAP). Smooth, blunt-edged or faceted, and pyramidal urocystoliths were usually MAP. Jackstone shapes were almost always silica. Botryoidal (grape-like clusters) urocystoliths were likely to be oxalates. Breeds with high relative likelihood of urocystoliths included: English Bulldog, Pekingese, Pug, Welsh Corgi, and West Highland White Terrier. Breeds with low relative likelihood of urocystolith production included: German Shepherd Dog, Shar-Pei, and German Shorthaired Pointer. About 94% of urocystoliths produced in females or spayed females were MAP, whereas males and neutered males produced a greater assortment. CONCLUSIONS AND CLINICAL RELEVANCE: For pure mineral composition urocystoliths, trends in mineral type among breeds and between sexes can be exploited clinically in the diagnosis and management of urolith-related disease. Size and shape, used in conjunction with age, breed, and sex, can facilitate pure urocystolith mineral type prediction.

Reliability of single urine and serum samples for estimation of 24-hour urinary uric acid excretion in six healthy beagles.

Urine uric acid-to-urine creatinine ratios (UUA:UC), urine uric acid concentrations, urine uric acid concentrations corrected for glomerular filtration rate, and urinary uric acid fractional excretions were compared with 24-hour urinary uric acid excretions measured in 6 healthy adult female Beagles. Comparisons, using correlation analysis, were made when dogs consumed a 10.4% protein (dry weight), casein-based diet and a 31.4% protein (dry weight), meat-based diet. The UUA:UC, urine uric acid concentrations corrected for glomerular filtration rate, and urinary uric acid fractional excretions were not reliable estimates of 24-hour urinary uric acid excretions during consumption of either diet. Urine uric acid concentrations in samples collected 2, 4, 6, and 24 hours after initiation of collection correlated with 24-hour urinary uric acid excretions when dogs consumed the casein-based diet; correlation was not found at any time interval when dogs consumed the meat-based diet. Therefore, determination of 24-hour urinary uric acid excretion is recommended because UUA:UC are unreliable.

Bioavailability and pharmacokinetics of intravenously and orally administered allopurinol in healthy beagles.

OBJECTIVES: To determine bioavailability and pharmacokinetic parameters for allopurinol and its active metabolite, oxypurinol. ANIMALS: 6 healthy, reproductively intact female Beagles, 4.9 to 5.2 years old, and weighing 9.5 to 11.5 kg. PROCEDURE: In the first part of the study, allopurinol was administered IV at a dosage of 10 mg/kg of body weight to 3 dogs and 5 mg/kg to 3 dogs; the sequence was then reversed. In the second part of the study, allopurinol was administered orally at a dosage of 15 mg/kg to 3 dogs and 7.5 mg/kg to 3 dogs; the sequence was then reversed. In the third part of the study, allopurinol was administered IV (10 mg/kg), orally (15 mg/kg) with food, and orally (15 mg/kg) without food. Plasma samples were obtained at timed intervals, and concentrations of allopurinol and oxypurinol were determined. RESULTS: Maximal plasma allopurinol concentration and area under plasma allopurinol and oxypurinol concentration-time curves were 2 times greater when dogs were given 10 mg of allopurinol/kg IV, compared with 5 mg/kg, and when dogs were given 15 mg of allopurinol/kg orally, compared with 7.5 mg/kg. Allopurinol elimination half-life, time to reach maximal plasma oxypurinol concentration, and oxypurinol elimination half-life were significantly greater when dogs received 10 mg of allopurinol/kg IV, compared with 5 mg/kg, and when dogs received 15 mg of allopurinol/kg orally, compared with 7.5 mg/kg. CONCLUSIONS: Elimination of allopurinol is dependent on nonlinear enzyme kinetics. The bioavailability of allopurinol, and pharmacokinetic parameters of allopurinol and oxypurinol after oral administration of allopurinol, are not affected by administration with food. CLINICAL RELEVANCE: A dose threshold exists beyond which additional allopurinol would not substantially further inhibit xanthine oxidase activity. Oral administration of > 15 mg of allopurinol/kg to dogs would not be expected to result in greater reduction of plasma and urine uric acid concentrations. Also, allopurinol may be administered to dogs for dissolution or prevention of urate uroliths without regard to time of feeding.

Influence of two diets on pharmacokinetic parameters of allopurinol and oxypurinol in healthy beagles.

OBJECTIVES: To determine whether diet influences the metabolism of IV administered allopurinol in healthy dogs. ANIMALS: 6 healthy female Beagles, 4.9 to 5.2 years old and weighing 9.6 to 11.5 kg. PROCEDURES: Allopurinol was administered IV (10 mg/kg) while dogs consumed a 10.4% protein (dry weight), casein-based diet or a 31.4% (dry weight), meat-based diet. After each dose, plasma samples were obtained at timed intervals, and concentrations of allopurinol and its active metabolite, oxypurinol, were determined by high-performance liquid chromatography. An iterative, nonlinear regression analytical program was used to determine the weighted least-squares, best-fit curves for plasma allopurinol and oxypurinol concentration-time data. From these data, pharmacokinetic parameters were calculated. RESULTS: Pharmacokinetic parameters for allopurinol and oxypurinol were not different when comparing the effect of diet. CONCLUSION: There is no influence of diet on pharmacokinetic parameters of allopurinol or oxypurinol. CLINICAL RELEVANCE: In contrast to observations in human beings, allopurinol metabolism is not influenced by diet. Therefore, formation of xanthine-containing calculi in dogs consuming a high-protein diet and receiving allopurinol is probably not attributable to alteration of allopurinol metabolism.