Short communication: Vitamin D status and responses in dairy cows naturally infected with Mycobacterium avium ssp. paratuberculosis.

Serum samples were obtained from Holstein dairy control cows and cows naturally infected with Mycobacterium avium ssp. paratuberculosis (MAP) to evaluate the effects of disease status on serum 25-hydroxyvitamin D3 (25OHD3) levels. Disease status was stratified for infected cows into asymptomatic, subclinical infection (n = 25), and cows demonstrating clinical signs (n = 20), along with noninfected control (n = 12) cows for comparison. In addition, portions of the ileocecal valve were taken from a subsample of cows (n = 5 per treatment group) at necropsy and processed for RNA sequencing gene transcription studies. Genes associated with vitamin D metabolism were queried to determine any association between infection and gene expression. Serum 25OHD3 levels were significantly lower in cows in the clinical stage of disease compared with either cows in the subclinical stage and noninfected control cows. Differential expression for genes associated with the vitamin D pathway such as CYP27A1, CYP27B1, vitamin D-binding protein (DBP), and IFNG was dependent upon infection status. An upregulation of CYP27A1 was noted for cows in subclinical status, whereas CYP27B1 expression was enhanced for clinical cows. Increased expression of vitamin D-binding protein was observed for infected cattle, regardless of infection status. In summary, decreases in circulating 25OHD3 for animals with clinical disease may suggest that these cows have reduced innate immune responses, thereby influencing the ability of animals to fight infection.

Evaluation of a dedicated MDCT protocol using iterative image reconstruction after cervical spine trauma.

AIM: To evaluate radiation exposure for 64-row computed tomography (CT) of the cervical spine comparing two optimized protocols using filtered back projection (FBP) and adaptive statistical iterative reconstruction (ASIR), respectively. MATERIALS AND METHODS: Sixty-seven studies using FBP (scanner 1) were retrospectively compared with 80 studies using ASIR (scanner 2). The key scanning parameters were identical (120 kV dose modulation, 64 × 0.625 mm collimation, pitch 0.531:1). In protocol 2, the noise index (NI) was increased from 5 to 25, and ASIR and the high-definition (HD) mode were used. The scan length, CT dose index (CTDI), and dose-length product (DLP) were recorded. The image quality was analysed subjectively by using a three-point scale (0; 1; 2), and objectively by using a region of interest (ROI) analysis. Mann-Whitney U and Wilcoxon's test were used. RESULTS: In the FBP group, the mean CTDI was 21.43 mGy, mean scan length 186.3 mm, and mean DLP 441.15 mGy cm. In the ASIR group, the mean CTDI was 9.57 mGy, mean scan length 195.21 mm, and mean DLP 204.23 mGy cm. The differences were significant for CTDI and DLP (p < 0.001) and scan length (p = 0.01). There was no significant difference in the subjective image quality (p > 0.05). The estimated mean effective dose decreased from 2.38 mSv (FBP) to 1.10 mSv (ASIR). CONCLUSION: The radiation dose of 64-row MDCT can be reduced to a level comparable to plain radiography without loss of subjective image quality by implementation of ASIR in a dedicated cervical spine trauma protocol. These results might contribute to an improved relative risk-to-benefit ratio and support the justification of CT as a first-line imaging tool to evaluate cervical spine trauma.

Type 2 diabetes affects hippocampus volume differentially in men and women.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been shown to result in medical complications on several organ systems including the kidneys, eyes, cardiovascular system, and most recently described the brain, including the hippocampus. There is also evidence that females are disproportionately affected by these medical complications. Brain volume reductions have also been associated with chronic low-grade inflammation and dyslipidaemia. This study investigated the relationships among T2DM, gender, inflammation, dyslipidaemia, and hippocampal volumes. METHOD: Participant groups consisted of 40 obese adults with T2DM and 47 lean adults, group-matched on age, gender, race, and education. Each participant underwent medical examination including a standard panel of blood tests, a magnetic resonance imaging, and cognitive evaluation. RESULTS: We show that there is a gender difference in the association of T2DM and hippocampal volumes: diabetic women are most affected despite having better glucose control than their male counterparts. Although females with T2DM had disproportionately lower high density lipoprotein as well as better haemoglobin A1c, neither of these results explained why females with T2DM had the smallest hippocampal volumes. CONCLUSIONS: These important findings indicate that in addition to the higher rate of traditional medical complication, females with T2DM are likely to suffer more brain complications than males. These observations, if supported by larger studies, suggest that in the future gender could be considered when customizing diabetes treatment.

Cardiovascular variability during treatment with haloperidol, olanzapine or risperidone in recent-onset schizophrenia.

This study aimed to investigate the effects of treatment with haloperidol, olanzapine and risperidone on cardiovascular variability in patients with recent-onset schizophrenia by means of spectral analysis. Unmedicated patients (n = 18) had a higher mean heart rate and a tendency for a lower high-frequency power of heart rate variability than healthy control subjects (n = 57), indicating a decreased cardiac vagal control in unmedicated patients with schizophrenia. Patients treated with haloperidol (n = 10) showed significantly lower low-frequency power of heart rate and systolic blood pressure variability compared with olanzapine-treated patients, suggesting that haloperidol attenuated sympathetic functioning. On the contrary, olanzapine-treated patients (n = 10) showed the highest power in the low-frequency range of heart rate and systolic blood pressure variability, suggesting an increased sympathetic cardiac functioning. No significant effects of risperidone (n = 13) were found. None of the antipsychotic agents differed in their parasympathetic cardiovascular effects. We conclude that young, unmedicated patients with schizophrenia differed from controls in their parasympathetic functioning, but the antipsychotic agents haloperidol, risperidone and olanzapine induced only minor cardiovascular side effects.

Adaptation of epithelial sodium-dependent phosphate transport in jejunum and kidney of hens to variations in dietary phosphorus intake.

The objective of this study was to explore the homeostatic response of jejunal and renal epithelia regarding the inorganic phosphate (P(i)) transport capacities to variations in dietary total phosphorus (tP) supply in hens. Adaptive processes were determined by quantitative measures of intake and excretion, P(i) transport studies across brush border membranes, and semiquantitative detection of sodium-dependent phosphate transporters (NaPi II) based on mRNA expression in the jejunum and kidney. Twelve hens (4/group) were adapted to 3 tP feeding levels in a pair-fed manner (60 g/d): low P diet with 0.073% tP, medium P diet with 0.204% tP, and high P diet with 0.343% tP. Excretion was measured during the last 5 d of a 16-d feeding period. After slaughtering, jejunal mucosa and renal cortex were removed. Tissues were used for (32)P uptake studies in brush-border membrane vesicles by rapid filtration technique and NaPi II mRNA expression studies by northern analyses. Plasma P(i) concentrations were additionally measured. The NaPi II transporter mRNA could specifically be detected in chicken jejunum and kidney. Functional parameters of Na(+)-dependent P(i) transport indicated that these transporters were involved in chicken P(i) transport across the apical membranes of jejunal and renal epithelia. Increased tP intake resulted in an increased overall tP excretion. Correlating individual data from all animals by linear regression highlighted that the adaptive decrease of renal P(i) transport capacity and NaPi IIa mRNA expression was associated with an increase in plasma P(i) levels and resulted in a higher tP excretion. Jejunal P(i) transport capacity and NaPi IIb mRNA expression did not react to variations in dietary tP supply. In conclusion, the homeostatic response was mainly based on the adaptive capacity of the kidney in hens.

Efficacy and safety of combination therapy using high- or low-dose hydrochlorothiazide with valsartan or other Angiotensin-receptor blockers.

Only a minority of patients treated for hypertension achieve controlled blood pressure (BP) levels. Therapy with fixed-dose combinations of an angiotensinreceptor blocker (ARB) and low-dose hydrochlorothiazide (HCTZ) is commonly prescribed but not always sufficient to achieve the target BP. The efficacy and safety of the fixed-dose combination of valsartan 160 mg and HCTZ 25 mg was evaluated in patients in whom BP had not been controlled with a fixed-dose combination of another ARB and low-dose HCTZ (12.5 mg) in a multicenter trial. After a wash-out period for antihypertensive drugs, patients with a mean sitting diastolic BP (DBP) at trough (3)100 mm Hg but <110 mm Hg were treated with candesartan cilexetil 16 mg plus HCTZ 12.5 mg or telmisartan 80 mg plus HCTZ 12.5 mg for 4 weeks (phase 1). Patients whose BP was still uncontrolled (DBP (3)90 mm Hg) after 4 weeks of therapy were then given valsartan 160 mg plus HCTZ 25 mg for an additional 4 weeks (phase 2). The primary efficacy parameter was the reduction in DBP between week 4 and week 8 in the intention-to-treat (ITT) population. BP reduction during phase 1 was -14.3+/-11.3/-7.5+/-3.9 mm Hg. DBP was controlled in 26% of the patients after phase 1. In patients treated with valsartan 160 mg plus HCTZ 25 mg during phase 2, DBP decreased by an additional 10.3+/-6.5 mm Hg and the mean sitting systolic BP (SBP) by an additional 11.0+/-11.7 mm Hg. The additional decrease was significant (P<.0001) for both parameters and independent of the fixed-dose combination used during phase 1. Among patients whose BP remained uncontrolled during phase 1, 74% achieved a controlled DBP after phase 2. The incidence of adverse events during both phases was comparably low and the results of laboratory tests were unremarkable. Treatment with valsartan 160 mg/HCTZ 25 mg offered a substantial benefit for patients with hypertension not controlled with the combination of candesartan cilexetil 16 mg or telmisartan 80 mg and low dose HCTZ, while maintaining a comparable safety and tolerability profile.

Refractory depression: mechanisms and evaluation of radically open dialectical behaviour therapy (RO-DBT) [REFRAMED]: protocol for randomised trial.

INTRODUCTION: Only 30-40% of depressed patients treated with medication achieve full remission. Studies that change medication or augment it by psychotherapy achieve only limited benefits, in part because current treatments are not designed for chronic and complex patients. Previous trials have excluded high-risk patients and those with comorbid personality disorder. Radically Open Dialectical Behaviour Therapy (RO-DBT) is a novel, transdiagnostic treatment for disorders of emotional over-control. The REFRAMED trial aims to evaluate the effectiveness and cost-effectiveness of RO-DBT for patients with treatment-resistant depression. METHODS AND ANALYSIS: REFRAMED is a multicentre randomised controlled trial, comparing 7 months of individual and group RO-DBT treatment with treatment as usual (TAU). Our primary outcome measure is depressive symptoms 12 months after randomisation. We shall estimate the cost-effectiveness of RO-DBT by cost per quality-adjusted life year. Causal analyses will explore the mechanisms by which RO-DBT is effective. ETHICS AND DISSEMINATION: The National Research Ethics Service (NRES) Committee South Central - Southampton A first granted ethical approval on 20 June 2011, reference number 11/SC/0146. TRIAL REGISTRATION NUMBER: ISRCTN85784627.

Identification of talinolol metabolites in urine of man, dog, rat and mouse after oral administration by high-performance liquid chromatography-thermospray tandem mass spectrometry.

A new specific HPLC-TSP-MS/MS assay for identification of beta-blocking drug talinolol and its metabolites in urinary samples of man, dog, rat and mouse after single oral administration has been developed. Centrifuged urines were directly injected into the HPLC-TSP-MS system. Based on thermospray MS/MS studies of 10 reference compounds, several selective CID-MS/MS reactions were found, which were typical of substructure elements of potential phase I metabolites. In this way the differentiation of various stereochemical positions of the hydroxyl group in the cyclohexyl ring moiety of metabolites was possible. Renal metabolic profiles for all investigated species were generated by HPLC-multiple reaction monitoring (MRM). The detected metabolites were characterized by TSP full scan and MS/MS analysis in relation to synthesized reference compounds. The major metabolic pathway in all species results in the hydroxylation of the cyclohexylring moiety of talinolol. In dog urine, a phase II metabolite, the O-glucuronide of talinolol (I) was found. In order to identify this structure, the use of electrospray ionization was also necessary.

Cerebral white matter and retinal arterial health in hypertension and type 2 diabetes mellitus.

We examined 33 hypertensive (22 with comorbid type 2 diabetes mellitus (T2DM)) and 29 normotensive (8 with T2DM) middle-aged and elderly adults, comparable in age and education. Relative to normotensive participants, those with hypertension, in addition to a higher prevalence of periventricular white matter (WM) lesions, had significantly lower WM microstructural integrity of major fiber tracts as seen with MRI-based diffusion tensor imaging. Among participants with hypertension, those with co-morbid T2DM (n = 22) had more widespread WM pathology than those without T2DM (n = 11). Furthermore and consistent with previous research, both hypertension and T2DM were related to decreased retinal arterial diameter. Further exploratory analysis demonstrated that the observed retinal arteriolar narrowing among individual with hypertension was associated with widespread subclinical losses in WM microstructural integrity and these associations were present predominantly in the frontal lobe. We found that T2DM adds to the damaging effects of hypertension on cerebral WM, and notably these effects were independent of age and body mass index. Given that the decrease in retinal arteriolar diameter may be a biomarker for parallel pathology in cerebral arterioles, our data suggest that the frontal lobe may be particularly vulnerable to microvascular damage in the presence of hypertension and T2DM.

Invasion success of the bumblebee, Bombus terrestris, despite a drastic genetic bottleneck.

In early 1992, the European bumblebee, Bombus terrestris, was first seen in Tasmania and currently has spread to most of the island. Here, we report on the genetic structure, using micro-satellites, of the invading population from samples collected in the years 1998-2000, a few years after the first sighting of the species in its new area. The data show that the Tasmanian population has a very low genetic diversity, with less than half of the allelic richness (Richness=2.89 alleles; H(exp)=0.591) and lower levels of heterozygosity as compared to populations in New Zealand (4.24 alleles; H(exp)=0.729) and Europe (5.08 alleles; H(exp)=0.826). In addition, the genetic data suggest that the invasion must have happened once, probably around late 1991, and was the result of very few, perhaps only two, individuals arriving in Tasmania. Furthermore, these founders came from the New Zealand population. Today, the population in the south of Tasmania seems to act as a source population from which individuals migrate into other parts of the state. A similar source-sink structure seems also the case for New Zealand. The data show that B. terrestris is a highly invasive species capable of establishing itself even after a dramatic genetic bottleneck. B. terrestris may be an invasive species due to the haplo-diploid sex determination system, which exposes recessive, deleterious mutations to selection. Offspring of such purged lines may then be able to tolerate high levels of inbreeding.

Phytase effects on the efficiency of utilisation and blood concentrations of phosphorus and calcium in Pekin ducks.

1. The objective was to study the effects of a supplementation of a 6-phytase derived from the Peniophora lycii gene in the White Pekin duck. 2. In two balance studies, low-phosphorus (P) diets consisting mainly of maize, solvent extracted soybean meal and solvent extracted sunflower meal were supplemented with phytase up to concentrations of 1500 U/kg (Study 1) or 2000 U/kg (Study 2). Each diet (phytase level) was fed to 8 to 10 individually penned ducks. The intake and excretion of each animal was measured for 5 consecutive days when ducks were in their third week of life. Responses were described by nonlinear regression. 3. Although the basal diets from the two studies were similar in ingredient composition, efficiencies of P utilisation (P accretion/P intake x 100) for the unsupplemented basal diets were 39% in Study 1 and 30% in Study 2. Phytase supplementation significantly improved P utilisation up to levels of about 55% in both studies. A plateau in P utilisation with an increase in phytase supplementation was achieved in Study 2, but not in Study 1. The enzyme was more efficient in Study 2 than in Study 1 at low rates of supplementation. Utilisation of calcium (Ca) was significantly improved by phytase supplementation. Accretions of P and Ca increased at a constant ratio. 4. In a 5-week growth study, diets with an intentionally marginal P level were used. Diets were fed either unsupplemented or supplemented with 1000 or 10,000 U/kg of phytase. Eight pens of 10 sex-separated ducks each (4 pens per sex) were allocated to each dietary treatment. 5. Phytase significantly improved the growth of ducks of both sexes between d 1 and 21, but not between d 22 and 35. Feed conversion rate was not affected by treatment. Blood serum phosphate concentrations, but not calcium, were significantly increased by phytase supplementation. Blood concentrations of creatinine, aspartate aminotransferase and lactate dehydrogenase remained unaffected while alanine aminotransferase was significantly reduced by phytase supplementation. 6. It was concluded that the efficacy of a microbial phytase varies even under similar experimental conditions. Differences in intrinsic phytase activity of maize/soybean meal-based diets may be responsible for this. The 6-phytase used has the potential to improve the utilisation of plant P in duck feeding. A plateau in response was reached above 1500 U/kg.

Intervention to increase seat belt use at a primary care center.

BACKGROUND: Increasing seat belt use represents an ideal opportunity for preventive health care in family practice. Little evidence exists, however, that primary care physicians can increase safety belt use. METHODS: Three hundred twenty-six patients seen in a rural primary care center were randomized to either a control or intervention group. Before their health care examination, patients completed a short questionnaire concerning seat belt use and then viewed a 6-minute videotape explaining reasons to wear seat belts (intervention) or espousing general preventive health care guidelines with no mention of seat belts (control). In 6 months the questionnaire was again administered with no further intervention. RESULTS: Two hundred forty-three (74.5 percent) patients completed both baseline and 6-month questionnaires. Seat belt use increased significantly from baseline to 6 months for the intervention (22 to 37.3 percent, P = 0.00052) and control (20 to 33.6 percent, P = 0.00085) groups; however, the difference between the increase in the intervention (37.3 percent) and control (33.6 percent) groups at 6 months was insignificant (P = 0.641). The most common reasons for not using seat belts were forgetfulness (40.3 percent), fear of being trapped (26.7 percent), and lack of comfort (21.8 percent). CONCLUSIONS: Seat belt use increased in this study, although the intervention videotape was no better than the control videotape at increasing restraint use. This increase in use supports office-based intervention to improve seat belt use, but further research is needed to clarify the mechanism and extent of change possible.

Physician documentation of diabetes care: use of a diabetes flow sheet and patient education clinic.

We assessed two interventions designed to improve the care of patients with diabetes mellitus by documenting the complications of their disease. These were a flow sheet, included with outpatient medical records, and a weekly patient education clinic, in which a nurse educator provided individualized instruction to patients with diabetes. Physician compliance with recommendations of the National Diabetes Advisory Board for diabetes care was measured before (n = 45) and after (n = 158) these interventions. The numbers of referrals to ophthalmologists increased from 22% to 46%, urinalyses increased from 58% to 77%, and lower extremity examinations increased from 36% to 61%. Nutrition education documentation increased from 51% to 69%, and diabetes education documentation increased from 31% to 61%. These results suggest that a significant improvement in physicians' documentation of care of patients with diabetes can be achieved by using a flow sheet and a diabetes patient education clinic.

A hospital microwave system for library telecommunication.

The medical library of the Olin E. Teague Veterans' Center needed access to an online integrated library system at a site eighty miles away. The center already operated a tower-to-tower microwave for teleconferencing and the library was able to use this as a temporary means of communication with the distant online system. The microwave link performed satisfactorily, leading to consideration of its use for other library applications.

[Pharmacologic effects in combined use of oxyfedrine and beta-acetyldiogoxin]. / Uber pharmakologische Wirkungen bei der kombinierten Anwendung von Oxyfedrin mit beta-Acetyldigoxin

In guinea pigs the toxic effect of beta-acetyldigoxin was not increased by simultaneously administered 3-(beta-hydroxy-alpha-methyl-phenethyl-amino)-3'-methoxy-propiophenone (oxy-fedrine). There was no evidence of a potentiation of the glycoside effect by the combination with oxyfedrine (ildamen-Novodigal). The threshold dose for arrhythmia was increased: typical glycoside tachyarrhythmias only occurred after higher infused doses. In anesthetized dogs with heart failure by overdosed pentobarbital, the therapeutic effects of beta-acetyldigoxin were sustained and enhanced by oxyfedrine.

[Acute poisoning with L-triiodothyroinine, L-thyroxine and phendimetrazine bitartrate with suicidal intention]. / Akute Intoxikation mit L-Trijodthyronin, L-Thyroxin und Phendimetrazinbitartrat aus suizidaler Absicht

It is reported on an acute intoxication after application of 8 mg L-thyroxin, 2 mg L-triiodotyronine (200 tablets Thyreotom) and 4.5 g hendimetrazine bitartrate (100 tablets Sedafamem). The clinical picture is described. An endangering of the vital function of the organism was not observed. The symptoms disappeared after 4 days. The pharmacological aspects of the intoxication after application of the hormone of the thyroid gland, its significance for the pathogenesis of the thyreotoxic crisis and its therapy are discussed

A new reporter gene system suited for cell-free protein synthesis and high-throughput screening in small reaction volumes.

The properties of M-hirudin as a new reporter gene system were examined using rabbit reticulocyte lysate for cell-free protein expression. In contrast to the luciferase gene, in vitro translation of M-hirudin is highly robust against changes in concentrations of K+ (and Rb+). In addition, M-hirudin can be detected very sensitively using a reasonably priced fluorimetric thrombin assay. To show that the new reporter gene system is well suited for (u)HTS-applications, cell-free synthesis as well as the fluorimetric assay of M-hirudin were carried out in nanotiter and microtiter plates, respectively.

[D-thyroxin in the therapy of type IIa and IIb hyperlipoproteinemias]. / D-Thyroxin in der Therapie von Hyperlipoproteinämien des Typs IIa und IIb.

21 patients with hyperlipoproteinaemias of type IIa and IIb were treated with D-thyroxin (4 mg/die) after a placebo phase. The observed changes of the cholesterol and triglyceride level in the serum are described. Hypermetabolic and cardiac side effects did not appear in the patients. The possible sites of action of D-thyroxin in the intermediary lipid metabolism are discussed.

[Clinical value of N-acetyl-beta-D-glucosaminidase and alpha-galactosidase in liver diseases]. / Zur klinischen Wertigkeit der N-Azetyl-beta-D-Glukosamminidase and alpha-Galaktosidase bei Lebererkrankungen.

N-acetyl-beta-D-glucosaminidase is a lysosomal glycosidase, which participates in the catabolism of the mucopolysaccharides and of the glycoproteins. For the determination of this enzyme the production of the substrate and a modified methodology are described. Measurements of the activity were performed by 4-nitrophenyl-alpha-D-galactopyranoside and 4-nitrophenyl-N-acetyl-beta-D-glucosaminide as substrates. Examinations of this enzyme were performed in patients with acute virus hepatitis, chronic hepatitis, liver cirrhosis and healthy test persons. In acute hepatitis and liver cirrhosis and significant increase of enzyme is provable, but not in protracted hepatitis.