Time of Cold Ischemia and Delayed Graft Function in a Cohort of Renal Transplant Patients in a Reference Center.

There are many factors involved in the delayed graft function of a renal graft, with prolonged cold ischemia time being one of the most relevant. The aim of this study is to evaluate the relationship between the time of cold ischemia and the delayed graft function, and acute rejection and graft loss at 1 year of follow-up. A retrospective cohort of 347 renal transplant patients were evaluated during the years 2009-2013. The incidence of delayed graft function was 18.4% (n = 65). The cold ischemia time was an independent risk factor for delayed graft function (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.04-1.16). By grouping the time of cold ischemia by intervals, the risk of delayed graft function was greater in the 12-18 hours group (OR 2.06, 95% CI 1.02-4.15) and in the >18 hours group (OR 3.38, 95% CI 1.57-7.27). The risk of acute rejection did not increase with longer cold ischemia (p = 0.69), and cold ischemia time was not a risk factor for renal graft loss at 1-year follow-up (hazard ratio 0.97, 95% CI 0.88-1.06). In conclusion the time of cold ischemia (>12 hours) in renal transplant recipients of optimal deceased donors increases the risk of delayed graft function; however, this does not negatively impact the results in acute rejection or graft loss in the first year of the transplant.

High-Energy Emissions Induced by Air Density Fluctuations of Discharges.

Bursts of X-rays and γ-rays are observed from lightning and laboratory sparks. They are bremsstrahlung from energetic electrons interacting with neutral air molecules, but it is still unclear how the electrons achieve the required energies. It has been proposed that the enhanced electric field of streamers, found in the corona of leader tips, may account for the acceleration; however, their efficiency is questioned because of the relatively low production rate found in simulations. Here we emphasize that streamers usually are simulated with the assumption of homogeneous gas, which may not be the case on the small temporal and spatial scales of discharges. Since the streamer properties strongly depend on the reduced electric field E/n, where n is the neutral number density, fluctuations may potentially have a significant effect. To explore what might be expected if the assumption of homogeneity is relaxed, we conducted simple numerical experiments based on simulations of streamers in a neutral gas with a radial gradient in the neutral density, assumed to be created, for instance, by a previous spark. We also studied the effects of background electron density from previous discharges. We find that X-radiation and γ-radiation are enhanced when the on-axis air density is reduced by more than ∼25%. Pre-ionization tends to reduce the streamer field and thereby the production rate of high-energy electrons; however, the reduction is modest. The simulations suggest that fluctuations in the neutral densities, on the temporal and spacial scales of streamers, may be important for electron acceleration and bremsstrahlung radiation.

Clinical prediction rules for mortality in patients with pulmonary embolism and cancer to guide outpatient management: a meta-analysis.

Essentials Clinical prediction rules (CPRs) can stratify patients with pulmonary embolism (PE) and cancer. A meta-analysis was done to assess prognostic accuracy in CPRs for mortality in these patients. Eight studies evaluating ten CPRs were included in this study. CPRs should continue to be used with other patient factors for mortality risk stratification. SUMMARY: Background Cancer treatment is commonly complicated by pulmonary embolism (PE), which remains a leading cause of morbidity and mortality in these patients. Some guidelines recommend the use of clinical prediction rules (CPRs) to help clinicians identify patients at low risk of mortality and therefore guide care. Objective To determine and compare the accuracy of available CPRs for identifying cancer patients with PE at low risk of mortality. Methods A literature search of Medline and Scopus (January 2000 to August 2017) was performed. Studies deriving/validating ≥ 1 CPR for early post-PE all-cause mortality were included. A bivariate, random-effects model was used to pool sensitivity and specificity estimates for each CPR. Traditional random-effects meta-analysis was performed to estimate the weighted proportion of patients deemed at low risk of early mortality, mortality in low risk patients and odds ratios for death compared with higher-risk patients. Results Eight studies evaluating 10 CPRs were included. The highest sensitivities were observed with Hestia (98.1%, 95% confidence interval [CI] = 75.6-99.9%) and the EPIPHANY index (97.4%, 95% CI = 93.2-99.0%); sensitivities of remaining rules ranged from 59.9 to 96.6%. Of the six CPRs with sensitivities ≥ 95%, none had specificities > 33%. Random-effects meta-analysis suggested that 6.6-51.6% of cancer patients with PE were at low risk of mortality, 0-14.3% of low-risk patients died and low-risk patients had a 43-94% lower odds of death compared with those at higher risk. Conclusions Because of the limited total body of evidence regarding CPRs, their results, in conjunction with other pertinent patient-specific clinical factors, should continue to be used in identifying appropriate management for PE in patients with cancer.

Interobserver Variation in the Diagnosis of Neurologic Abnormalities in the Horse.

BACKGROUND: The diagnosis of equine protozoal myeloencephalitis (EPM) relies heavily on the clinical examination. The accurate identification of neurologic signs during a clinical examination is critical to the interpretation of laboratory results. OBJECTIVE: To investigate the level of agreement between board-certified veterinary internists when performing neurologic examinations in horses. ANIMALS: Ninety-seven horses admitted to the Veterinary Teaching Hospital at The Ohio State University from December 1997 to June 1998. METHODS: A prospective epidemiologic research design was used. Horses enrolled in the study were examined by the internist responsible for care of the horse, and later by an internist who was not aware of the presenting complaint or other patient history. Data were analyzed by descriptive statistics, and kappa (K) statistics were calculated to assess interobserver agreement. RESULTS: Ninety-seven horses were enrolled in the study. Overall, examiners, also referred to as observers, agreed that 60/97 (61.9%) were clinically abnormal, 21/97 (21.6%) were clinically normal, and the status of 16/97 (16.5%) of horses was contested. There was complete agreement among the examiners with regard to cranial nerve signs and involuntary movements. Disagreement involving severity of clinical signs occurred in 31 horses, and 25 of those horses (80.6%) were considered either normal or mildly affected by the primary observer. When examining the results of all paired clinical examinations for 11 different categories, there was wide variability in the results. When examiners rated the presence or absence of any neurologic abnormalities, lameness, or ataxia, the agreement among observers was either good or excellent for 80% of horses. When assessing truncal sway, the agreement among observers was good or excellent for 60% of the horses. When examining the horses for asymmetry of deficits, agreement was either good or excellent for 40% of the horses. Agreement among observers was excellent or good for only 20% of the horses when assessing muscle atrophy, spasticity (hypermetria), and overall assessment of the severity of neurologic abnormalities. CONCLUSIONS AND CLINICAL IMPORTANCE: This study underscores the subjectivity of the neurologic examination and demonstrates a reasonable level of agreement that may be achieved when different clinicians examine the same horse.

Sustained delivery of siRNA poly- and lipopolyplexes from porous macromer-crosslinked gelatin gels.

RNA interference (RNAi) is a promising technique to treat severe diseases on a pre-protein level. We and others postulate that the release of nanoparticle-complexed small interfering RNA (siRNA) from implanted biomaterials could provide structural support for tissue repair, combined with local siRNA transfection of invading and regenerating cells. In this study, we systematically investigated cross-linked gelatin based hydrogel formulations (cGEL) as degradable controlled release matrices for siRNA. Aiming at the definition of correlations between cGEL composition, siRNA nanoparticle formulation, release kinetics of complexed siRNA and transfection efficiency, we combined five different cGEL formulations and three transfection systems, i.e. polyplexes with polyethyleneimine (PEI), PEI in combination with liposomes (lipopolyplexes) and polyplexes based on tyrosin-modified PEI (P10Y). It was found that the distribution of these poly-/lipopolyplexes, when applied onto the negatively charged hydrogels, was strongly dependent on their zeta potential. Furthermore, siRNA release from the hydrogel was a multifactorial process, as diffusion, hydrogel degradation and nanoparticle decomplexation overlapped over time. This resulted in a prolonged release of siRNA for up to 21days. In the case of PEI complexes and lipopolyplexes, release kinetics depended on the cGEL formulation. In contrast, when employing P10Y polyplexes, an initial burst release was observed with no further release thereafter. Silencing activity was determined using constitutively luciferase-expressing SKOV-3-Luc reporter cells. Surface and bulk porosity in hydrogels was introduced by addition of soluble polyethylene glycol during fabrication, leading to improved knockdown. The rapid onset of knockdown efficacy will also provide the basis for the determination of long-term effects.

Dual-component collagenous peptide/reactive oligomer hydrogels as potential nerve guidance materials - from characterization to functionalization.

Toward a new generation of improved nerve guidance conduits (NGCs), novel biomaterials are required to address pressing clinical shortcomings in peripheral nerve regeneration (PNR) and to promote biological performance. A dual-component hydrogel system formed by cross-linking reaction between maleic anhydride groups in an oligomeric building block for cross-linking of free amine functionalities in partially hydrolyzed collagen is formulated for continuous processing and NGC fabrication. The influence of the gelation base is optimized for processing from a double syringe delivery system with a static mixer. A hydrophilic low-concentrated base was introduced to control network formation and to utilize highly reactive macromers for gelation. Cross-linking extent and building block conversion were improved and homogenous monoliths were fabricated. Chemically derivatized hydrogels were obtained by conversion of a fraction of anhydride groups in the oligomeric precursor with monovalent primary amine-containing grafting molecules prior to gelation. Network stability in functionalized hydrogels was maintained and cationic moieties were implement to the gel that promoted in vitro cell attachment and spreading irrespective of mechanical stiffness. A molding strategy was introduced that allowed for fabrication of flexible tubular conduits in tunable dimensions and with chemically patterned structures. These hydrogel-based conduits hold promise for the next generation NGCs with integrated chemical cues for PNR.

Protothecal bursitis after simultaneous kidney/liver transplantation: a case report and review.

Solid organ transplantation is an accepted therapy for end-stage diseases of the kidneys, liver, heart, and lungs. Unfortunately, transplantation is associated with infectious complications. Here, we present a case report of Prototheca wickerhamii olecranon bursitis and review all of the cases in solid organ transplant (SOT) recipients published in the literature to date. In our patient, the infection resolved with surgical therapy and limited antifungal therapy, and no symptoms have recurred over 24 months of follow-up. A review of the literature suggests that 50% of SOT recipients with Prototheca infection present with disseminated infection, and the overall mortality is 75%. More studies are required to determine the optimal management of protothecosis in this population.

External validation of the In-hospital Mortality for PulmonAry embolism using Claims daTa (IMPACT) multivariable prediction rule.

OBJECTIVE: To validate the In-hospital Mortality for PulmonAry embolism using Claims daTa (IMPACT) multivariable prediction rule using admission claims data. STUDY DESIGN: Retrospective claims database analysis. METHODS: This analysis was performed using Humana admission claims data from January 2007 to March 2014. We included adult patients admitted for their first PE during this period (International Classification of Diseases, ninth edition, Clinical Modification code of 415.1x in in the primary position or secondary position when accompanied by a primary code for a PE complication). The IMPACT rule, consisting of age plus 11 comorbidities, was used to estimate patients' probability of in-hospital mortality and classify risk. Low risk was defined as in-hospital mortality ≤ 1.5%. IMPACT was evaluated by evaluating prognostic test characteristic values and 95% confidence intervals (CIs). RESULTS: A total of 23,858 patients admitted for PE were included, and 3.3% died in-hospital. The IMPACT prediction rule classified 2371 (9.9%) as low-risk; with a sensitivity of 97.6%, 95% CI: 96.1-98.5, specificity of 10.2%, 95% CI: 9.8-10.6, negative and positive predictive values of 99.2% (95% CI: 98.7-99.5) and 3.5% (95% CI: 3.3-3.8) and c-statistic of 0.70, 95% CI: 0.0.68-0.72, for in-hospital mortality. IMPACT classified 42.7% of patients < 65 years old as low-risk; with a sensitivity, specificity and c-statistic of 85.0%, 95% CI: 77.4-90.5, 43.3%, 95% CI: 42.0-44.7 and 0.74, 95% CI: 0.69-0.78, respectively. CONCLUSION: The IMPACT prediction rule was valid when implemented in a database consisting largely of Medicare claims. Following further external validation and direct comparison to commonly used clinical prediction rules, IMPACT may become a valuable tool for payers and hospitals wishing to retrospectively assess whether their PE patients are being kept hospitalized for the optimal period of time.

Efficacy and safety of antihyperglycaemic drug regimens added to metformin and sulphonylurea therapy in Type 2 diabetes: a network meta-analysis.

AIM: To assess the efficacy and safety of third-line adjuvant antihyperglycaemic agents in people with Type 2 diabetes mellitus failing metformin and sulphonylurea combination therapy. METHODS: We searched MEDLINE, CENTRAL, clinicaltrials.gov and regulatory websites, and conducted a manual search of references in the identified studies. Randomized trials evaluating antihyperglycaemic agents in adults with Type 2 diabetes experiencing poor glycaemic control despite optimized metformin and sulphonylurea therapy (≥ 1500 mg metformin or maximum tolerated dose; ≥ 50% of maximum sulphonylurea dose for ≥ 3 weeks) were included. Data extraction included: study characteristics; change in HbA1c concentration; weight; systolic blood pressure; and relative risk of hypoglycaemia, urinary tract infections; and genital tract infections. A network meta-analysis was performed. RESULTS: A total of 20 trials evaluating 13 antihyperglycaemic agents were included. Compared with placebo/control, all antihyperglycaemic agents reduced HbA1c levels, albeit by differing magnitudes [range 7 mmol/mol (0.6%) for acarbose to 13 mmol/mol (1.20%) for liraglutide]. Sodium glucose cotransporter-2 inhibitors reduced weight (1.43-2.07 kg) whereas thiazolidinediones, glargine and sitagliptin caused weight gain (1.48-3.62 kg) compared with placebo/control. Sodium glucose cotransporter-2 inhibitors, rosiglitazone and liraglutide decreased systolic blood pressure compared with placebo/control, pioglitazone, glargine and sitagliptin (2.41-8.88 mm Hg). Glargine, thiazolidinediones, liraglutide, sitagliptin and canagliflozin increased hypoglycaemia risk compared with placebo/control (relative risk 1.92-7.47), while glargine and rosiglitazone increased hypoglycaemia compared with most antihyperglycaemic agents (relative risk 2.81-7.47). No antihyperglycaemic agent increased the risk of urinary tract infection, but canagliflozin increased the risk of genital tract infection by 3.9-fold compared with placebo/control. CONCLUSIONS: When added to metformin and a sulphonylurea, antihyperglycaemic agents had varying effects on efficacy and safety endpoints. These conclusions should be considered when clinicians choose between possible adjunctive agents.

Index clinical manifestation of venous thromboembolism predicts early recurrence type and frequency: a meta-analysis of randomized controlled trials.

BACKGROUND: Observational studies suggest index clinical manifestation of venous thromboembolism (VTE) predicts recurrence type. Data regarding the association between index manifestation and recurrence rates are conflicting. OBJECTIVES: To perform a meta-analysis of randomized controlled trials (RCTs) to determine the type and frequency of recurrent VTE (rVTE) in persons after an index deep vein thrombosis (DVT) or pulmonary embolism (PE). PATIENTS/METHODS: We searched bibliographic databases for RCTs of acute (early) treatment of rVTE in persons with an index DVT or PE (±DVT), enrolling ≥ 50 subjects anticoagulated ≥ 3-months and reporting types of rVTE. We pooled (random-effects) the proportion of rVTEs that were DVTs, PEs, and fatal PEs, the proportion of recurrent PEs that were fatal, and absolute rVTE rates. RESULTS: In nine RCTs (N = 13 640; 413 rVTEs) evaluating persons with an index PE; 66% (95% CI, 60-72%) of rVTEs were PE and 27% (95% CI, 22-33%) were fatal PE. Among 25 RCTs (N = 17 340; 692 rVTEs) evaluating persons with an index DVT, 36% (95% CI, 29-44%) experienced a recurrent PE and 10% (95% CI, 7-13%) a fatal PE. Recurrent PEs following an index PE had a higher fatality rate than after an index DVT (41%; 95% CI, 33-48% vs. 25%; 95% CI, 18-33%; P = 0.007). The rVTE rate was higher following an index DVT compared with a PE (2.6%; 95% CI, 1.6-3.8% vs. 4.9%; 95% CI, 4.0-6.0%; P = 0.002). CONCLUSIONS: Our meta-analysis suggests most rVTEs will be the same type as the index event. While index DVTs are associated with a higher rVTE rate than index PEs; recurrent PEs are associated with high fatality.

Histoplasmosis in renal transplant patients in an endemic area at a reference hospital in Medellin, Colombia.

BACKGROUND: Histoplasmosis is an uncommon systemic fungal infection, but it is potentially fatal in immunosuppressed populations. In Latin America, which is considered an endemic area for this mycosis, there have been no published reports regarding the incidence, clinical presentation, morbidity, and mortality of histoplasmosis in renal transplant patients. The objective of this study was to describe cases of histoplasmosis in renal transplant patients treated at the Pablo Tobon Uribe Hospital (Medellin, Colombia) between 2006 and 2013. METHODS: This is a descriptive, retrospective study. RESULTS: The incidence of histoplasmosis in our renal transplant population was 1.1%. The ages of the 9 patients (4 men and 5 women) ranged between 27 and 59 years. In 2 of these patients, histoplasmosis appeared during the first year after transplantation. At the time of transplantation, 66% of patients received induction with alemtuzumab; 88% had a prior rejection episode and required increased immunosuppressive medication; 88% had renal graft dysfunction with creatinine levels >1.5 mg/dL; and the primary clinical presentation was disseminated histoplasmosis followed by the pulmonary form of the disease. Diagnoses were performed by histology in 6 patients, blood culture in 2 patients, and antigenuria in 1 patient. Three patients required treatment with amphotericin B for the severity of their infection, and 2 of these patients died before receiving the cumulative dose of amphotericin B. The 7 remaining patients received itraconazole for 12 months and had a successful treatment response. Regarding complications, 2 patients had hemophagocytic syndrome. At the 1-year follow-up appointment, renal function remained stable in all patients, and no patients had acute rejection or required renal replacement therapy. Thus, the overall mortality rate observed was 22.2%. CONCLUSIONS: In this series, histoplasmosis in renal transplant patients presented as an aggressive opportunistic infection with a higher incidence than that previously reported in the literature. The following risk factors have been associated with histoplasmosis: renal graft dysfunction, previous acute rejection, immunosuppression with tacrolimus-mycophenolate, and induction with alemtuzumab. The clinical presentation of histoplasmosis was nonspecific, which complicated disease diagnosis, and the treatment regimens were highly toxic and associated with significant morbidity and mortality rates.

Cloning, comparative sequence analysis and mRNA expression of calcium-transporting genes in horses.

Epithelial calcium transport occurs by paracellular and transcellular mechanisms. Transcellular transport in intestinal and renal epithelia involves several transport proteins, including transient receptor potential vanilloid member 5 (TRPV5), member 6 (TRPV6), calbindin D9k (CB9), calbindin D28k (CB28), sodium calcium exchanger 1 (NCX1), plasma membrane calcium ATPase 1 (PMCA1), and the vitamin D receptor (VDR). We are interested in the horse because of its unique calcium physiology (high blood calcium, high intestinal calcium absorption, high renal excretion of calcium, low vitamin D concentrations), and because horses often have dysregulated calcium balance with various diseases. We cloned the mRNA for equine TRPV5, TRPV6, CB9, CB28, NCX1, PMCA1, and VDR, performed comparative mRNA and protein sequence analysis, and quantified their mRNA expression in the kidney and gastrointestinal tract. Sequence homology for the mRNAs and proteins was high among mammals (>75%), with fish having the lowest homology (<75%). TRPV5, TRPV6, and CB9 expression was higher in the duodenum and proximal jejunum and followed a similar expression pattern. CB28 expression was greatest in the kidney. PMCA1 and NCX1 expression was similar throughout the intestine, but in the kidney PMCA1 expression was higher. Based on our findings, the proximal small intestine is the main site for transcellular calcium transport, with TRPV6 and CB9 serving as the main transport proteins. In the kidney, TRPV6, CB28, and PMCA1 are likely more important. The low VDR expression in the equine small intestine and kidney relative to the large intestine, together with the reported high intestinal absorption and renal excretion of calcium, and low vitamin D concentrations suggests that epithelial calcium transport in horses is not as dependent on vitamin D as in other species.

Rapid calcitonin response to experimental hypercalcemia in healthy horses.

Calcium has important physiological functions, and disorders of calcium homeostasis are frequent in horses. We have made important progress understanding equine calcium homeostasis; however, limited information on equine calcitonin (CT) is available, in part because of the lack of validated CT assays. To determine the CT response to high ionized calcium (Ca(2+)) concentrations in healthy horses, we induced hypercalcemia in 10 healthy horses using a calcium gluconate 23% solution (5mg/kg; 120 mL/500 kg horse) infused over 4 min. Four horses were infused with 120 mL of 0.9% NaCl and used as controls. We validated a human-specific CT radioimmunoassay for use in horses. Serum Ca(2+) concentrations increased from 6.2+/-0.3mg/dL to 9.9+/-0.5mg/dL (4 min; P<0.01). Serum CT increased from 16.7+/-8.0 pg/mL to 87.1+/-55.8 pg/mL at 2 min, and 102.5+/-51.1 pg/mL at 4 min (P<0.01). Serum CT returned to baseline by 20 min, whereas serum Ca(2+) returned to baseline by 40 min. Of interest, CT concentrations returned to baseline despite hypercalcemia, suggesting thyroid gland C-cell CT depletion. Resting CT values higher than 40 pg/mL were considered abnormally elevated. No significant changes in serum Ca(2+) or CT concentrations were found in control horses. The coefficients of variation for the CT radioimmunoassay were lower than 11.9%. We conclude that the equine thyroid gland C-cell responds quickly to changes in extracellular Ca(2+) concentrations by secreting large quantities of CT into the systemic circulation, indicating that CT is important in equine calcium homeostasis. The human CT radioimmunoassay can be used to measure changes in equine CT.

Blood arginine vasopressin, adrenocorticotropin hormone, and cortisol concentrations at admission in septic and critically ill foals and their association with survival.

BACKGROUND: Sepsis is an important cause for neonatal foal mortality. The hypothalamic-pituitary-adrenal axis (HPAA) responses to sepsis are well documented in critically ill humans, but limited data exist in foals. The purpose of this study was to evaluate the HPAA response to sepsis in foals, and to associate these endocrine changes with survival. HYPOTHESIS: Blood concentrations of arginine vasopressin (AVP), adrenocorticotropin hormone (ACTH), and cortisol will be higher in septic foals as compared with sick nonseptic and healthy foals. The magnitude of increase in hormone concentration will be negatively associated with survival. ANIMALS: Fifty-one septic, 29 sick nonseptic, and 31 healthy foals of < or =7 days of age were included. METHODS: Blood was collected at admission for analysis. Foals with positive blood culture or sepsis score > or =14 were considered septic. Foals admitted with disease other than sepsis and healthy foals were used as controls. AVP, ACTH, and cortisol concentrations were measured using validated immunoassays. RESULTS: AVP, ACTH, and cortisol concentrations were increased in septic foals. Septic nonsurvivor foals (n = 26/51) had higher plasma ACTH and AVP concentrations than did survivors (n = 25/51). Some septic foals had normal or low cortisol concentrations despite increased ACTH, suggesting relative adrenal insufficiency. AVP, ACTH, and cortisol concentrations were higher in sick nonseptic foals compared with healthy foals. CONCLUSIONS AND CLINICAL IMPORTANCE: Increased plasma AVP and ACTH concentrations in septic foals were associated with mortality. Several septic foals had increased AVP : ACTH and ACTH : cortisol ratios, which indicates relative adenohypophyseal and adrenal insufficiency.

Report of the equine herpesvirus-1 Havermeyer Workshop, San Gimignano, Tuscany, June 2004.

Amongst the infectious diseases that threaten equine health, herpesviral infections remain a world wide cause of serious morbidity and mortality. Equine herpesvirus-1 infection is the most important pathogen, causing an array of disorders including epidemic respiratory disease abortion, neonatal foal death, myeloencephalopathy and chorioretinopathy. Despite intense scientific investigation, extensive use of vaccination, and established codes of practice for control of disease outbreaks, infection and disease remain common. While equine herpesvirus-1 infection remains a daunting challenge for immunoprophylaxis, many critical advances in equine immunology have resulted in studies of this virus, particularly related to MHC-restricted cytotoxicity in the horse. A workshop was convened in San Gimignano, Tuscany, Italy in June 2004, to bring together clinical and basic researchers in the field of equine herpesvirus-1 study to discuss the latest advances and future prospects for improving our understanding of these diseases, and equine immunity to herpesviral infection. This report highlights the new information that was the focus of this workshop, and is intended to summarize this material and identify the critical questions in the field.

Effects of dietary glycaemic response after exercise on blood concentrations of substrates used indirectly for muscle glycogenesis.

REASONS FOR PERFORMING STUDY: Exercise depletes muscle glycogen stores, which could subsequently impair performance. Muscle glycogen replenishment is determined by substrate availability. OBJECTIVES: To study the effects of feeding meals of varying glycaemic responses on blood concentrations of substrates used for glycogenesis in horses with exercise-induced glycogen depletion. METHODS: In a 3-way crossover study, 7 horses received each of 3 isocaloric diets for 72 h after undergoing glycogen-depleting exercise: 1) a high soluble-carbohydrate diet, which induced a high-glycaemic (HGI) response; 2 and 3) a low soluble-carbohydrate or a mixed soluble-carbohydrate diet (control group), which both induced a similar low-to-moderate glycaemic (LGI) response. Muscle biopsies and venous samples were collected before and up to 72 h after exercise. RESULTS: Feeding HGI diet resulted in a higher (P<0.001) rate of muscle glycogenesis over 72 h compared to LGI diets. Plasma glycerol, triglyceride, lactate, serum NEFA and total protein concentrations, and haematocrit were significantly (P<0.001) higher after compared to before exercise. Whereas no significant overall dietary effect was observed on these metabolites over 72 h, there was a tendency for glycerol, NEFA and triglyceride concentrations to be lower for LGI compared to HGI diets over 6 h after exercise (P<0.05; 1, 6 and 4-6 h after exercise, respectively). CONCLUSIONS: These data suggest that horses fed LGI meals after exercise had limited lipid utilisation without any significant shift of substrate utilisation toward gluconeogenesis, which could have contributed to the slower rate of muscle glycogenesis compared to horses fed HGI diets.

Parathyroid hormone (PTH) secretion, PTH mRNA and calcium-sensing receptor mRNA expression in equine parathyroid cells, and effects of interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha on equine parathyroid cell function.

Parathyroid hormone (PTH) is secreted by the chief cells of the parathyroid gland in response to changes in ionized calcium (Ca(2+)) concentrations. In this study, we measured PTH secretion, and PTH mRNA and calcium-sensing receptor (CaR) mRNA expression by equine parathyroid chief cells in vitro. We also evaluated the effects of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha on PTH secretion, and PTH and CaR mRNA expression. The relationship between PTH and Ca(2+) was inversely related. PTH secretion decreased from 100% (day 0) to 13% (day 30). PTH mRNA expression declined from 100% (day 0) to 25% (day 30). CaR mRNA decreased from 100% (day 0) to 16% (day 30). Chief cells exposed to high (2.0 mM) Ca(2+) concentrations had a lower PTH mRNA expression compared with low Ca(2+) concentrations. Ca(2+) concentrations had no effect on CaR mRNA expression. The inhibitory effect of high Ca(2+) concentrations on PTH secretion also declined over time. After day 10, there was no significant difference in PTH secretion between low and high Ca(2+ )concentrations. IL-1beta decreased both PTH secretion (75%) and PTH mRNA expression (73%), and resulted in a significant overexpression of CaR mRNA (up to 142%). The effects of IL-1beta were blocked by an IL-1 receptor antagonist. IL-1beta decreased the Ca(2+) set-point from 1.4 mM to 1.2 mM. IL-6 decreased PTH secretion (74%), but had no effect on PTH and CaR mRNA expression. TNF-alpha had no effect on PTH secretion, and PTH and CaR mRNA expression. In summary, the decreased responsiveness of parathyroid cells to Ca(2+) from 0 to 30 days can be explained, in part, by the reduced CaR expression. IL-1beta and IL-6 but not TNF-alpha affected parathyroid function in vitro and may be important in influencing PTH secretion in the septic horse.

Chronic pulmonary disease with radiographic interstitial opacity (interstitial pneumonia) in foals.

Twelve foals, age 3-9 months, examined at The Ohio State University Veterinary Teaching Hospital between 1995 and 2000 were diagnosed with chronic pulmonary disease associated with marked interstitial opacity on radiographic examination. The most characteristic features were a history of respiratory disease of 1-3 months duration, marked clinical signs of respiratory disease, failure to yield a consistent pathogen from tracheobronchial aspirates and a predominantly interstitial pattern on thoracic radiographs. We attributed these signs to chronic interstitial pneumonia. Foals were treated with broad spectrum antimicrobial and corticosteroid drugs. All 12 foals were discharged alive from hospital and, of the 10 available for follow-up, all were disease-free and performing to expectation 5 months to 5 years after discharge. We conclude that chronic interstitial pneumonia, occuring in foals, is associated with a good prognosis and that corticosteroid therapy may be useful in its treatment.

Intradermal testing in healthy horses and horses with chronic obstructive pulmonary disease, recurrent urticaria, or allergic dermatitis.

OBJECTIVE: To compare responses to a variety of intradermally injected allergens among healthy horses and horses with chronic obstructive pulmonary disease (COPD), recurrent urticaria (RU), and atopic dermatitis-insect hypersensitivity (allergic dermatitis [AD]). DESIGN: Case-control study. ANIMALS: 86 horses. PROCEDURE: Results of intradermal testing for horses with COPD, RU, or AD were compared with results for healthy horses. RESULTS: Compared with healthy horses, horses with COPD, RU, and AD were significantly more likely to have positive (> or = 3+) reactions to intradermal allergens (molds, weeds, trees, grasses-crops, and insects) 30 minutes (immediate reaction), 4 hours (late-phase reactions), and 24 hours (delayed-phase reactions) after exposure. In addition, diseased horses reacted to a significantly higher number of allergens in each allergen group than did healthy horses. CONCLUSIONS AND CLINICAL RELEVANCE: Reactions to individual allergens should not be used to determine that horses have hypersensitivity. Overall patterns of reactivity to intradermal allergens may be helpful in management when used in conjunction with a compatible history and evidence of potential exposure to allergens in horses with conditions associated with hypersensitivity to environmental allergens.

An enantioselective assay for (+/-)-modafinil.

Enantiomers of modafinil, (diphenylmethyl)sulphinyl-2-acetamide, were separated by an amylose tris[(S)-1-phenylethylcarbamate] chiral stationary phase, using acetonitrile: water (25:75 v/v) as mobile phase, with excellent selectivity (alpha=1.4) and resolution factors (R(s)=1.5). The assay involved a solid-phase extraction of the enantiomers of modafinil from plasma using a C(18) Cartridge. A good linear relationship was obtained in the concentration of 0.15-3 microg ml(-1) for each enantiomer. The method developed is sufficiently accurate and precise to be used for clinical samples and has a good selectivity with the two main circulating metabolites: the (diphenylmethyl)sulphinyl-2-acetic acid and (diphenylmethyl)sulphonyl-2-acetamide. The use of a polysaccharide-based column on multimodal elution was explored in developing the method.