Robust Fermi-Surface Morphology of CeRhIn_{5} across the Putative Field-Induced Quantum Critical Point.

We report a comprehensive de Haas-van Alphen (dHvA) study of the heavy-fermion material CeRhIn_{5} in magnetic fields up to 70 T. Several dHvA frequencies gradually emerge at high fields as a result of magnetic breakdown. Among them is the thermodynamically important ß_{1} branch, which has not been observed so far. Comparison of our angle-dependent dHvA spectra with those of the non-4f compound LaRhIn_{5} and with band-structure calculations evidences that the Ce 4f electrons in CeRhIn_{5} remain localized over the whole field range. This rules out any significant Fermi-surface reconstruction, either at the suggested nematic phase transition at B^{*}≈30 T or at the putative quantum critical point at B_{c}≃50 T. Our results rather demonstrate the robustness of the Fermi surface and the localized nature of the 4f electrons inside and outside of the antiferromagnetic phase.

Providing systematic detailed information on medication upon hospital discharge as an important step towards improved transitional care.

WHAT IS KNOWN AND OBJECTIVE: Good communication between hospital and primary care physicians (PCPs) is important for the continuity of patient care in the transition phase following hospital treatment. Drug-related problems and medication errors may occur at that interface. Discharge letters often lack a structured medication report at the end and therefore may not provide the reasons for medication changes, resulting in low adherence rates. The objectives were to develop a structured medication report as part of the discharge letter, to evaluate the impact of the medication report in ischaemic stroke patients and to identify the most important issues in the transitional care process of stroke patients. METHODS: First, a structured medication report was developed. Thereafter, the impact of this new medication report on clinical practice was evaluated with an open, prospective, interventional two-phase study conducted at the Klinikum Fulda gAG (Germany), which included patients with ischaemic stroke and >2 drugs in the discharge medication. In the control group (CG), the neurologist included the current medication in the discharge letter. In the intervention group (IG), the clinical pharmacist added the detailed information to a medication report. To evaluate adherence to discharge medication, the PCP was interviewed 3 months after hospital discharge about the medication. Adherence was measured with respect to the entire medication regimen, antithrombotic and cholesterol-lowering drugs and discontinued medication. The most important issues in the transitional care for patients with ischaemic stroke were identified on the basis of the secondary stroke prevention and cardiovascular risk factors. RESULTS AND DISCUSSION: Overall, 312 patients were enrolled in the study with 156 patients in each group. By providing detailed information in the newly developed discharge letter, adherence increased significantly from 83·3% (CG) to 90·9% (IG; P = 0·01). Significant differences between the CG and IG were found with regard to adherence to both antithrombotic drugs [83·8% CG vs. 91·9% IG (P = 0·033)] and statin therapy [69·8% CG vs. 87·7% IG (P < 0·001)]. WHAT IS NEW AND CONCLUSION: The use of a structured medication report as part of the discharge letter leads to improved adherence to hospital discharge medication.

Repellency of DEET, picaridin, and three essential oils to Triatoma rubida (Hemiptera: Reduviidae: Triatominae).

The kissing bug, Triatoma rubida (Uhler) is a common hematophagous bug in Tucson, AZ, and is responsible for causing severe allergic reactions in some bitten individuals. DEET, picaridin, tea tree oil, peppermint oil, and citronella oil were tested for repellency to T. rubida and its ability to probe and feed on a small restrained rat. No long range repellency was observed with any of the test materials. The lowest repellent concentrations observed were: 10% DEET, 7% picaridin; 30% tea tree oil, 3.3% peppermint oil, and 0.165% citronella oil. Only citronella oil was able to stop all probing and feeding by T. rubida. Citronella oil appears to be a promising potential repellent to prevent sleeping people from being bitten by kissing bugs.

Use of AgomiR and AntagomiR technologies to alter satellite cell proliferation in vitro, miRNA expression, and muscle fiber hypertrophy in intrauterine growth-restricted lambs.

Introduction: microRNAs (miRNAs) are small non-coding RNAs that work at the posttranscriptional level to repress gene expression. Several miRNAs are preferentially expressed in skeletal muscle and participate in myogenesis. This research was conducted to alter endogenous miRNA expression in skeletal muscle to promote muscle hypertrophy. Methods: Two experiments were conducted using mimic/agomiR or antagomir technologies to alter miRNA expression and examine changes in myoblast proliferation in vitro (experiment 1) and muscle hypertrophy in vivo (experiment 2). In vitro experiments found that antagomiR-22-3p and mimic-127 increased myoblast proliferation compared to other miRNA treatments or controls. These miRNA treatments, antagomiR-22-3p (ANT22) and agomiR-127 (AGO127), were then used for intramuscular injections in longissimus muscle. Results and discussion: The use of antagomiR or mimic/agomiR treatments down-regulated or up-regulated, respectively, miRNA expression for that miRNA of interest. Expression of predicted target KIF3B mRNA for miR-127 was up-regulated and ACVR2a mRNA was up-regulated for miR-22-3p. ANT22 injection also up-regulated the major regulator of protein synthesis (mTOR). Proteomic analyses identified 11 proteins for AGO127 and 9 proteins for ANT22 that were differentially expressed. Muscle fiber type and cross-sectional area were altered for ANT22 treatments to transition fibers to a more oxidative state. The use of agomiR and antagomir technologies allows us to alter miRNA expression in vitro and in vivo to enhance myoblast proliferation and alter muscle fiber hypertrophy in IUGR lambs during early postnatal growth.

Quality of life after intensity-modulated radiotherapy for prostate cancer with a hydrogel spacer. Matched-pair analysis.

BACKGROUND: Hydrogel spacer is an innovative method to protect the rectal wall during prostate cancer radiotherapy. Clinical effects are not well known. METHODS: Patients have been surveyed before, at the last day, and 2-3 months after radiotherapy using a validated questionnaire (Expanded Prostate Cancer Index Composite). Median dose to the prostate in the spacer subgroup (SP) was 78 Gy in 2 Gy fractions. The results were independently compared with two matched-pair subgroups (treated conventionally without spacer): 3D conformal 70.2 Gy in 1.8 Gy fractions (3DCRT) and intensity-modulated radiotherapy (IMRT) 76 Gy in 2 Gy fractions. There were 28 patients in each of the three groups. RESULTS: Baseline mean bowel bother scores were 96 points in all subgroups. Similar mean changes (SP 16, 3DCRT 14, IMRT 17 points) were observed at the end of radiotherapy. The smallest difference resulted in the spacer subgroup 2-3 months after radiotherapy (SP 2, 3DCRT 8, IMRT 6 points). Bowel bother scores were only significantly different in comparison to baseline levels in the spacer subgroup. The percentage of patients reporting moderate/big bother with specific symptoms did not increase for any item (urgency, frequency, diarrhoea, incontinence, bloody stools, pain). CONCLUSION: Moderate bowel quality-of-life changes can be expected during radiotherapy irrespective of spacer application or total dose. Advantages with a spacer can be expected a few weeks after treatment.

Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas. Results of a prospective phase II study.

PURPOSE: Dose escalations above 60 Gy based on MRI have not led to prognostic benefits in glioblastoma patients yet. With positron emission tomography (PET) using [(18)F]fluorethyl-L-tyrosine (FET), tumor coverage can be optimized with the option of regional dose escalation in the area of viable tumor tissue. METHODS AND MATERIALS: In a prospective phase II study (January 2008 to December 2009), 22 patients (median age 55 years) received radiochemotherapy after surgery. The radiotherapy was performed as an MRI and FET-PET-based integrated-boost intensity-modulated radiotherapy (IMRT). The prescribed dose was 72 and 60 Gy (single dose 2.4 and 2.0 Gy, respectively) for the FET-PET- and MR-based PTV-FET((72 Gy)) and PTV-MR((60 Gy)). FET-PET and MRI were performed routinely for follow-up. Quality of life and cognitive aspects were recorded by the EORTC-QLQ-C30/QLQ Brain20 and Mini-Mental Status Examination (MMSE), while the therapy-related toxicity was recorded using the CTC3.0 and RTOG scores. RESULTS: Median overall survival (OS) and disease-free survival (DFS) were 14.8 and 7.8 months, respectively. All local relapses were detected at least partly within the 95% dose volume of PTV-MR((60 Gy)). No relevant radiotherapy-related side effects were observed (excepted alopecia). In 2 patients, a pseudoprogression was observed in the MRI. Tumor progression could be excluded by FET-PET and was confirmed in further MRI and FET-PET imaging. No significant changes were observed in MMSE scores and in the EORTC QLQ-C30/QLQ-Brain20 questionnaires. CONCLUSION: Our dose escalation concept with a total dose of 72 Gy, based on FET-PET, did not lead to a survival benefit. Acute and late toxicity were not increased, compared with historical controls and published dose-escalation studies.

Development of a classification system for drug-related problems in the hospital setting (APS-Doc) and assessment of the inter-rater reliability.

WHAT IS KNOWN AND OBJECTIVE: Identifying, preventing and resolving drug-related problems (DRP) is an important issue in the pharmaceutical care process. Because DRPs have been detected in a more systematic way, the need for a classification system to document, classify and evaluate the collected data has become necessary. The objective was to develop a classification system for DRPs within the hospital setting, to evaluate the practicality and to assess the inter-rater reliability. METHODS: All DRPs defined in PI-Doc and PCNE, which are relevant in the hospital setting, were included. Further relevant DRPs identified in other projects in a hospital setting as well as DRPs from the daily work on the ward were collected, and a short description of each DRP was written. A prospective study was conducted at Klinikum Fulda, Germany, in both a non-surgical and a surgical setting to explore whether the new classification system is suitable to classify DRPs in clinics with different specifications. For assessing the inter-rater reliability, 24 standardized case reports were provided. All participants classified them independently. The inter-rater reliability was analysed using Kappa coefficient. RESULTS AND DISCUSSION: A classification system for DRPs in the hospital setting (APS-Doc) was established with 10 main categories and 48 subcategories. Practicality was assessed in 250 patients in a non-surgical ward as well as in 100 patients in a surgical ward. The inter-rater agreement was 0·68 (95% CI, 0·66-0·69) for main categories, which comprises substantial agreement. Moderate agreement (κ = 0·58; 95% CI, 0·58-0·59) was demonstrated for the subcategories. WHAT IS NEW AND CONCLUSION: A new hierarchical classification system for DRPs in the hospital setting has been developed. APS-Doc seems suitable for various parts of the medication process such as medication reconciliation and drug therapy within both non-surgical and surgical wards. Inter-rater reliability was found to be substantial in the main categories and moderate in the subcategories.

[Cerebral venous thrombosis and subdural haematoma: complications of spontaneous intracranial hypotension]. / Sinus-/Hirnvenenthrombose und Subduralhämatome als Komplikationen eines spontanen Liquorunterdrucksyndroms.

We report on the case of a spontaneous intracranial hypotension with subdural hygroma, as well as cerebral venous thrombosis (CVT), both known complications of intracranial hypotension. The 45-year-old patient was subsequently treated - according to current guidelines for CVT - with anticoagulation, but developed subdural haematoma (SDH), which required neurosurgical treatment. Our case highlights the complex pathophysiological sequelae of intracranial hypotension, as well as the occasionally difficult treatment decisions. Subdural hygroma probably predisposes patients to SDH during anticoagulation. Thus, the potential benefit of anticoagulation needs to be weighed against the risk of SDH on an individual basis.

Mycotoxin ingestion during late gestation alters placentome structure, cotyledon transcriptome, and fetal development in pregnant sheep.

Ergot alkaloids, a class of mycotoxins, induce vasoconstriction when consumed by animals and humans. Pregnant ewes (n = 16; 81.2 kg ± 7.7) were assigned fed endophyte-infected tall fescue seed (E+; 4.14 µg ergovaline + ergovalinine/g seed) or a control diet (CON; 0 µg ergovaline + ergovalinine) for increasing duration during late gestation (from gd86 to gd110 or gd133) to examine changes in placentome morphology and mRNA transcriptome, and fetal development. Exposure to E+ fescue reduced serum prolactin concentrations at gd110 and gd133 demonstrating treatment efficacy. For control ewes, cotyledon and total placentome weights decreased with advancing gestation due to remodeling of placental tissues; however, cotyledon and placentome weight did not change with advancing gestation in E+ fed ewes. Fetal brain sparing was evident in E+ exposed fetuses at gd110 and gd133 compared to CON, which demonstrates asymmetrical growth and intrauterine growth restriction. Mycotoxin exposure (E+) resulted in differential expression of 22 genes in the cotyledon tissue at gd110 but only one gene at gd133 compared to CON. These results suggest that the response to mycotoxin exposure in the pregnant sheep model has an immediate impact on placental remodeling and fetal development that persists throughout the duration of the exposure period.

5-Hydroxytryptophan strongly stimulates serotonin synthesis in Holstein steers.

Although serotonin has been extensively studied in many species, there is a lack of information in ruminants, and no research has been evaluated if its precursor, 5-hydroxytryptophan (5-HTP), administered into the abomasum may be used as a means to manipulate serotonin metabolism. Thus, the objective of this study was to evaluate if intra-abomasal infusion of 5-HTP increases circulating serotonin in the steer. Eight Holstein steers (471 ± 8.9 kg) were used in a replicated 4 × 4 Latin Square design experiment. The treatments were intra-abomasal infusion of 5-HTP at 0.5, 1, 2.5, and 5 mg/kg BW. Blood was collected at 0, 2, 4, 6, 8, and 24 h after infusion. The serum concentration of 5-HTP increased quadratically (P = 0.005) with a peak at 2 h after administration. The 5-HTP administration increased (P < 0.05) serum serotonin in comparison with baseline with no difference (P > 0.05) between the doses of 5-HTP. When 5-HTP was dosed at 2.5 mg/kg BW or higher, intake decreased, and there was an altered manure consistency. The serum 5-hydroxyindole acetic acid concentrations followed the same pattern as 5-HTP. Plasma glucose content was not affected (P > 0.05) by 5-HTP dosing. However, free fatty acids concentration in the plasma was lower (P > 0.05) compared with baseline for the infusion levels of 0.5 and 1 mg/kg BW. Intra-abomasal infusion of 5-HTP efficiently increases serum serotonin cattle.

Residual effects of abomasal 5-hydroxytryptophan administration on serotonin metabolism in cattle.

Studies of serotonin in animal husbandry has received growing interest. However, there is limited information about serotonin manipulation using 5-HTP administered postruminally and its residual effects in cattle. The objective of this study was to evaluate the effectiveness of 5-HTP infused into the abomasum for enhancing circulating serotonin in cattle. Four Holstein steers (487 ± 7.6 kg) fitted with ruminal cannulas were used in a 4 × 4 Latin Square design experiment. The treatments were intra-abomasal infusion of 5-HTP at 0, 0.25, 0.5, and 1 mg/kg BW. Blood was collected from the jugular vein of each steer at -60, -30, 0, 30, 60, 120, 240, and 480 min from 5-HTP infusion for basal and short term evaluation and, at 1, 2, 4, and 7 d after 5-HTP infusion for long term evaluation. Dry matter intake was not affected (P > 0.05) by intra-abomasal infusions. The half-life of 5-HTP was dose-independent (128 min). The serum 5-HTP, serotonin, and 5-hydroxyindoleacetic acid area under the curve increased (P < 0.05) linearly with an increased dose of 5-HTP. Serum 5-HTP reached peak concentration in approximately 30 min after dosing while serum and plasma serotonin peaked after 240 min postinfusion. Serotonin was greater than control for all 5-HTP doses 1 d and 2 d after infusion in serum and plasma, respectively. Intra-abomasal infusion of 5-HTP at doses up to 1 mg/ kg BW increases circulating serotonin for up 2 days.

Pattern of postruminal administration of l-tryptophan affects blood serotonin in cattle.

Serotonin (5-HT) has many important functions in both central and peripheral nervous systems. Although it has been demonstrated that manipulation of serotonin metabolism is possible in many species, there is limited information about l-tryptophan (TRP), a serotonin precursor, in cattle, and these provide conflicting results. Furthermore, there is no study evaluating how different patterns of intra-abomasal infusion of TRP impact circulating 5-HT. The objective of this study was to evaluate if intra-abomasal infusion patterns of TRP can affect circulating 5-HT and other metabolites from TRP metabolism in the plasma and serum and circulating glucose and insulin in cattle. Eight ruminally cannulated Holstein steers were used in a replicated 4 × 4 Latin square design. Each received intra-abomasal water infusion (control) or intra-abomasal TRP infusion (50 mg/kg BW) in 3 different patterns: a pulse infusion once a day (pulse once), pulse infusion twice a day (pulse twice), or continuous infusion (continuous). For continuous treatment, the TRP dose was diluted in tap water and infused by a peristaltic pump (300 mL/h). To equalize conditions, the other treatments had a water infusion (300 mL/h). The steers were fed every 2 h, and blood was collected from a jugular vein catheter every 4 h for 24 h after the initial infusion. Urine produced during the 24 h period was collected. Serum and plasma TRP, 5-HT and kynurenine, plasma glucose, and serum insulin concentrations were analyzed. Urine was analyzed for concentrations of 5-hydroxyindoleacetic acid. Both serum TRP and kynurenine were increased (P < 0.05) by all TRP infusion treatments, but concentrations in pulse dose treatments were greater than those in continuous infusion. Serum 5-HT increased (P < 0.05) with both pulse TRP infusion treatments; however, the continuous TRP infusion did not increase the serum 5-HT. Plasma 5-HT, glucose, and insulin had a tendency to increase with TRP pulse infusions. The urinary 5-hydroxyindoleacetic acid excretion was highest for pulse dose treatments. An acute supply of TRP in 1 or 2 daily doses increases serum 5-HT and increases circulating glucose and insulin in cattle. The TRP and kynurenine concentrations are similar in plasma and serum. However, the serum 5-HT concentration is more responsive to TRP administration than plasma.

Multiple VH gene segments encode murine antistreptococcal antibodies.

Most mouse strains are able to mount a diverse antibody response against group A streptococcal carbohydrate (GAC). We have previously reported that murine anti-GAC antibodies are for the most part restricted to IgM and IgG3 subclasses. In addition, despite extensive heterogeneity in their isoelectric focusing patterns, greater than 50% of A/J anti-GAC antibodies share a common light chain defined by spectrotypic and idiotypic (VK1GAC) criteria. We have used protein and DNA sequencing strategies to examine the genetic basis of diversity in murine anti-GAC antibodies. In particular, we report that, (a) multiple, closely homologous VH gene segments contribute to the generation of anti-GAC antibodies, (b) a common framework sequence, related to the VK27 subgroup, probably defines VK1GAC, and (c) the A/J anti-GAC VH regions and BALB/c anti-inulin VH sequences are 95% homologous at the protein level and are likely encoded by overlapping VH gene families. Lastly, we discuss the genetic mechanisms that might permit the evolution of multiple, closely homologous germline VH gene segments in the context of highly divergent flanking region sequences.

Case-control study of radon and lung cancer in New Jersey.

Radon is known to cause lung cancer in humans; however, there remain uncertainties about the effects associated with residential exposures. This case-control study of residential radon and lung cancer was conducted in five counties in New Jersey and involved 561 cases and 740 controls. A year long alpha-track detector measurement of radon was completed for approximately 93% of all residences lived in at the time of interview (a total of 2,063). While the odds ratios (ORs) for whole data were suggestive of an increased risk for exposures >75 Bq m(-3), these associations were not statistically significant. The adjusted excess OR (EOR) per 100 Bq m(-3) was -0.13 (95% CI: -0.30 to 0.44) for males, 0.29 (95% CI: -0.12 to 1.70) for females and 0.05 (95% CI: -0.14 to 0.56) for all subjects combined. An analysis of radon effects by histological type of lung cancer showed that the OR was strongest for small/oat cell carcinomas in both males and females. There was no statistical heterogeneity of radon effects by demographic factors (age at disease occurrence, education level and type of respondent). Analysis by categories of smoking status, frequency or duration did not modify the risk estimates of radon on lung cancer. The findings of this study are consistent with an earlier population-based study of radon and lung cancer among New Jersey women, and with the North American pooling of case control radon seven studies, including the previous New Jersey study. Several uncertainties regarding radon measurements and assumptions of exposure history may have resulted in underestimation of a true exposure-response relationship.

Changes in net portal nutrient flux in response to weaning transition and ionophore supplementation in dairy calves.

Dairy calf weaning is associated with ketone concentrations that exceed the levels occurring in adults, and weaning represents a potential energy loss that may be mitigated by ionophore supplementation. To assess the effects of weaning and ionophore supplementation on net nutrient flux across portal-drained viscera (PDV) tissues in dairy calves, concentrations of glucose, acetoacetate (ACAC), beta-hydroxybutyrate (BHBA), nonesterified fatty acids, volatile fatty acids, lactate, pyruvate, insulin, and glucagon and PDV flux rates were determined in Jersey bull calves (n = 19) at 35, 56, 84, and 112 d of age. Calves were randomly assigned at birth to either a commercial pelleted starter without (CON) or with lasalocid (TRT; 83 mg/kg of dry matter). Calves were fed only milk replacer from d 3 to 34 (d 3 to 20 = 454 g/d; d 21 to 34 = 568 g/d). After blood sampling on d 35, calves received replacer (d 35 to 41 = 454 g/d; d 42 to 48 = 227 g/d) and had free access to the CON or TRT starter, and from d 49 to 112 they received CON or TRT ad libitum. Catheters were implanted in the portal vein and in the mesenteric vein and artery between d 21 and 28. Blood flow was measured by continuous infusion of p-aminohippurate into the mesenteric vein. Six serial samples were taken at 30-min intervals from the arterial and portal vein catheters simultaneously. Portal blood flow increased with age but did not differ between CON and TRT calves. Glucose was released preweaning and was extracted postweaning by PDV, but was not affected by ionophore. The portal flux of nonesterified fatty acids was not different from zero during any of the 4 sample ages. Fluxes of ACAC and BHBA in CON and TRT calves went from no measurable flux preweaning to a postweaning PDV release that peaked at d 84, but the d-84 release of ACAC and BHBA was lower in TRT calves. The portal flux of volatile fatty acids increased with age, and PDV release of both butyrate and propionate was lower at d 84 in TRT than in CON calves. However, TRT calves had a greater PDV release of lactate on d 84, partially compensating for the lower release of propionate. Glucagon was greater in CON than in TRT calves at d 84 and could be a response to the elevated ketogenesis observed in CON calves during this period. Changes in the metabolic profile and nutrient flux of transition calves were demonstrated in response to weaning and ionophore supplementation. Inclusion of an ionophore appeared to moderate alimentary output at a postweaning period (d 84) at which ketone concentrations have the potential to exceed the whole animal capacity for utilization.

Tall fescue ergot alkaloids are vasoactive in equine vasculature.

Mares grazing endophyte-infected () tall fescue () typically exhibit reproductive dysfunction rather than problems associated with peripheral vasoconstriction as a primary sign of the fescue toxicosis syndrome. Research using Doppler ultrasonography demonstrated that consumption of endophyte-infected tall fescue seed causes measurable vasoconstriction in the medial palmar artery. The objective of this study was to evaluate contractile responses of medial palmar artery and vein to increasing concentrations of various tall fescue alkaloids. Medial palmar arteries and veins were collected immediately following euthanasia from 23 horses of mixed breed, age, and gender from both forelimbs, and uterine arteries were collected from females ( = 12). Vessels were separated, cleaned of excess connective and adipose tissue, divided into 2- to 3-mm cross-sections, and suspended in a multimyograph chamber with continuously oxygenated Krebs-Henseleit buffer (95% O/5% CO; pH 7.4; 37°C). Following a 90-min equilibration and recovery from reference compound exposure, increasing concentrations of norepinephrine, 5-hydroxytryptamine, ergotamine, and ergonovine for the palmar artery and vein and uterine artery and ergovaline, ergocryptine, ergocristine, ergocornine, and lysergic acid for the palmar artery and vein were added to assess vasoactivity. Data were normalized as a percentage of contractile response induced by the reference compound addition and analyzed as a completely randomized design. Both norepinephrine and serotonin were vasoactive in all 3 types of blood vessels. Neither ergotamine nor ergonovine were vasoactive in the uterine artery. All alkaloids tested with the palmar artery and vein produced a contractile response, except that neither the palmar artery nor the palmar vein responded to lysergic acid ( > 0.05). Ergovaline was the most vasoactive ergot alkaloid in both the palmar artery and the palmar vein ( < 0.05) followed by ergonovine, whereas out of the 4 remaining ergopeptine alkaloids tested, ergocristine induced the lowest contractile response. Although horses do not outwardly appear to be affected by peripheral vasoconstriction as observed in cattle, these data indicate that tall fescue alkaloids are vasoactive and suggest that potential exists for peripheral vascular effects of tall fescue alkaloids in horses. This does not appear to be the case for the uterine artery, and future research should be directed at understanding how ergot alkaloids cause equine reproductive dysfunction.

Effects of weaning and ionophore supplementation on selected blood metabolites and growth in dairy calves.

Dairy calf weaning results in blood ketone concentrations in excess of mature rates of use and can result in excretion of ketones in urine representing a loss of energy. Lasalocid is frequently supplemented as an anticoccidial agent in calf starters; however, in mature ruminants it is known to alter molar ratios of ruminal volatile fatty acids (VFA). Effects of weaning transition and postweaning ionophore supplementation on body weight, dry matter (DM) intake, average daily gain (ADG), and blood concentrations of glucose, acetoacetate, beta-hydroxybutyrate (BHBA), lactate, pyruvate, nonesterified fatty acids (NEFA), VFA, insulin, and glucagon were examined using Jersey bull calves (n = 24) over 16 wk. Calves were blocked into groups of 2 according to birth date and weight and randomly assigned to receive either a commercial pelleted starter (control), or the same diet containing lasalocid (TRT; 83 mg/kg of DM). Calves were fed milk replacer from d 3 to 34 (d 3 to 20 = 454 g/d at 12% solids; d 21 to 34 = 568 g/d at 15% solids), from d 35 to 48 calves received both replacer (d 35 to 41 = 454 g/d; d 42 to 38 = 227 g/d) and free access to control or TRT starter, and from d 49 to 112 received ad libitum control or TRT. Body weight and jugular blood metabolite concentrations were measured and recorded weekly. Postweaning DM intake, average daily gain, and feed:gain did not differ between control and TRT calves. Glucose and NEFA concentrations did not differ between control and TRT, but declined with age. Insulin and glucagon concentrations did not differ between control and TRT, but glucagon concentrations increased with weaning. Total VFA significantly increased following introduction of solid feed at d 35 in both groups with an apparent 1-wk lag in TRT VFA increases compared with control. Jugular acetate and butyrate concentrations were greater in control calves than TRT calves during wk 7. Propionate concentrations did not differ between control and TRT at any time following weaning. Blood BHBA concentrations were greater in control than TRT during wk 8 and 9. Thus, consumption of starter supplemented with lasalocid delayed peak acetate and butyrate and lowered peak BHBA concentrations. However, supplementation at concentrations currently recommended for control of coccidiosis did not appear to be sufficient to enhance growth or efficiency during the wk 7 to 16 postweaning interval for this sample size.

Statistical methods for the analysis of tumor multiplicity data.

The fit of tumor multiplicity data from 93 mouse skin, lung, and liver carcinogenicity experiments to Poisson, negative binomial, and normal distributions was studied. The data were fitted well by the negative binomial distribution. This distribution has two parameters, the mean tumor multiplicity and an exponent determined by the interanimal homogeneity of tumor response. The value of the latter parameter was related to animal strain and the target tissue studied in the carcinogenicity experiments. The null distribution of the two-sample likelihood ratio test based on the negative binomial with common exponent model for tumor multiplicity data was shown by simulation studies to be approximately chi 2 with 1 d.f. Simulation also indicated that the likelihood ratio test has sufficiently better performance when the negative binomial model is valid to make its use more attractive than the more commonly used Wilcoxon test or Student t test. Charts for estimating the number of animals per group that are required to detect specified differences in tumor multiplicities are provided for several commonly used assays.

Development of lymphoma in the thymus of AKR mice treated with the lymphomagenic virus SL 3-3.

A chronological study of the individual thymic lobes of young AKR mice after neonatal inoculation of the oncogenic AKR retrovirus SL 3-3 was performed. 100% of mice treated in this manner develop lymphoma between 60 and 100 days of age. A search for early lymphoma cells in individual thymi was carried out by inoculating the thymocytes subcutaneously in syngeneic and intrathymically in syngeneic and semisyngeneic recipients. Tumor progression was observed in animals between 48 and 60 days of age. These animals have: (a) normal weight lobes, in which no lymphoma cells could be detected, (b) thymus-dependent lymphoma cells, in one or both normal weight lobes; (c) thymus-independent lymphoma cells, found in lobes of normal weight as well as in thymi enlarged by lymphoma cells. Thymocyte characteristics of virus-treated animals of 21 to 63 days of age were compared with those of age-matched controls. Beginning at 28 days a concordant, progressive with time, increase of thymocyte surface staining for the viral envelope glycoprotein gp70 was seen in all lobes from virus-treated animals. Evaluation of cell surface markers by two-color fluorescence with antibodies to CD4 and CD8 showed that after 50 days of age, thymic lobes with and without lymphomas had nonspecific, but marked, alterations of the typical thymocyte surface marker pattern. No characteristic CD4, CD8 surface phenotype was found in primary lymphomas. Using probes for the T-cell receptor J beta 2 gene segments and the Akv ecotropic virus gp70 envelope genes, oligoclonality in J beta 2 rearrangements and clonality using the Akv env genes was demonstrated in thymi with the thymus-dependent phenotype. In lymphomas T-cell receptor beta gene probes showed either oligoclonality or clonality. Clonal virus integrations were found in these lymphomas. These experiments suggest the following series of events in virus-accelerated AKR lymphomagenesis. First, lymphoma cells arise which are initially thymus-dependent and can appear in one or simultaneously in both thymic lobes. These progress to become thymus-independent, fully autonomous, tumor cells. Thymocytes close to or at the time of the initial transformation event show a marked disorder of differentiation defined by the alterations in the CD4, CD8 surface phenotype distribution.

Mouse monoclonal antibody to a melanoma-carcinoma-associated antigen synthesized by a human melanoma cell line propagated in serum-free medium.

A monoclonal antibody, F11, was produced against a tumor-associated antigen from the spent medium of the M14 human malignant melanoma cell line which was grown continuously in serum-free medium. Ouchterlony double-diffusion study revealed that the F11 monoclonal antibody is an immunoglobulin G1. The F11 monoclonal antibody reacted positively with seven of eight (88%) melanoma, five of five (100%) carcinoma, zero to five normal, and zero of two lymphoblastoid cell lines by indirect immunofluorescence test. Also, by indirect immunofluorescence test, F11 monoclonal antibody reacted with cryostat sections from four of five (80%) melanomas, six of seven (86%) carcinomas, zero of one benign nevus, and zero of two benign breast diseases. By the indirect avidin:biotin:peroxidase complex immunoperoxidase method, the F11 monoclonal antibody reacted positively with cryostat sections from five of five (100%) melanomas, five of five (100%) breast cancers, two of two (100%) colon cancers, zero of one benign nevus, and zero of one Hodgkin's disease spleen. Thus, the tumor-associated antigen that the F11 monoclonal antibody recognizes appears to be expressed by melanomas and carcinomas, hence the designation melanoma-carcinoma-associated antigen. Microscopic observations disclosed that the melanoma-carcinoma-associated antigen is present in the cytoplasm, on the membrane of melanoma and carcinoma cells, and in the lumen of glandular structures of breast and colon carcinomas. The molecular weight of the melanoma-carcinoma-associated antigen in spent medium from the M14 CEM cell line is 100,000 as determined by sodium dodecyl sulfate:polyacrylamide gel electrophoretic analysis of indirect immunoprecipitates obtained with the F11 monoclonal antibody.