Acute toxicities in proton therapy for head and neck cancer - A matched analysis of the DAHANCA 35 feasibility study.

Background and purpose: As preparation for a national randomized study comparing proton radiotherapy to photon radiotherapy, DAHANCA 35, we performed a non-randomized pilot study to investigate patient selection, logistics, planning, and treatment delivery. With the present study, as a comprehensive safety analysis, we want to compare toxicity during and up to two months after therapy to a historically matched group of patients treated with photon radiotherapy. Materials and methods: 62 patients treated with protons were matched to 124 patients who received photon treatment outside a protocol. Available data were retrieved from the DAHANCA database. Patients were matched on treatment centre, concurrent chemotherapy, tumour site, stage, p16 status for oropharynx cancers. Selection of patients for proton therapy was based on comparative treatment plans with a NTCP reduction for dysphagia and xerostomia at six months. Results: Baseline characteristics between groups were well balanced, except for the type of drug used concurrently; more photon patients received Carboplatin (21.2 % vs 5.8 %, p = 0.01). Proton therapy was associated with significantly less weight loss at the end of treatment, mean weight loss of 3 % for protons and 5 % for photons (p < 0.001). There were more grade 3 skin reactions and grade 3 mucositis after proton treatment compared with photons at the end of treatment, Risk Ratio (RR) 1.9 (95 % CI: 1.01-3.5, p = 0.04) and RR 1.5 (95 % CI: 1.3-1.7, p < 0.001), respectively. All differences resolved at follow up two months after treatment. There were no significant differences between groups on opioid use, use of feeding tubes, or hospitalization during the observation period. Conclusion: Proton treatment resulted in excess objective mucositis and dermatitis, which was transient and did not seem to negatively influence weight or treatment compliance and intensity. Selection bias was likely especially since NTCP models were used for selection of proton treatment and photon treated patients were matched manually. We are currently including patients in a randomized controlled trial.

Fractional exhaled nitric oxide as a potential biomarker for radiation pneumonitis in patients with non-small cell lung cancer: A pilot study.

INTRODUCTION: The aim of the study was to investigate repetitive fractional exhaled nitric oxide (FeNO) measurements during high-dose radiation therapy (HDRT) and to evaluate the use of FeNO to predict symptomatic radiation pneumonitis (RP) in patients being treated for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A total of 50 patients with NSCLC referred for HDRT were enrolled. FeNO was measured at baseline, weekly during HDRT, one month- and every third month after HDRT for a one-year follow-up period. The mean FeNO(visit 0-6) was calculated using the arithmetic mean of the baseline and weekly measurements during HDRT. Patients with grade ≥ 2 of RP according to the Common Terminology Criteria for Adverse Events (CTCAE) were considered symptomatic. RESULTS: A total of 42 patients completed HDRT and weekly FeNO measurements. Grade ≥ 2 of RP was diagnosed in 24 (57%) patients. The mean FeNO(visit 0-6) ±â€¯standard deviation in patients with and without RP was 15.0 ±â€¯7.1 ppb (95%CI: 12.0-18.0) and 10.3 ±â€¯3.4 ppb (95%CI: 8.6-11.9) respectively with significant differences between the groups (p = 0.0169, 95%CI: 2.3-2.6). The leave-one-out cross-validated cut-off value of the mean FeNO(visit 0-6) ≥ 14.8 ppb was predictive of grade ≥ 2 RP with a specificity of 71% and a positive predictive value of 78%. CONCLUSIONS: The mean FeNO(visit 0-6) in patients with symptomatic RP after HDRT for NSCLC was significantly higher than in patients without RP and may serve as a potential biomarker for RP.

Maternal fish oil supplementation during lactation is associated with reduced height at 13 years of age and higher blood pressure in boys only.

Dietary long-chain n-3 PUFA (n-3 LCPUFA) in infancy may have long-term effects on lifestyle disease risk. The present follow-up study investigated whether maternal fish oil (FO) supplementation during lactation affected growth and blood pressure in adolescents and whether the effects differed between boys and girls. Mother-infant pairs (n 103) completed a randomised controlled trial with FO (1·5 g/d n-3 LCPUFA) or olive oil (OO) supplements during the first 4 months of lactation; forty-seven mother-infant pairs with high fish intake were followed-up for 4 months as the reference group. We also followed-up 100 children with assessment of growth, blood pressure, diet by FFQ and physical activity by 7-d accelerometry at 13·5 (sd 0·4) years of age. Dried whole-blood fatty acid composition was analysed in a subgroup (n 49). At 13 years of age, whole-blood n-3 LCPUFA, diet, physical activity and body composition did not differ between the three groups. The children from the FO group were 3·4 (95 % CI 0·2, 6·6) cm shorter (P=0·035) than those from the OO group, and tended to have less advanced puberty (P=0·068), which explained the difference in height. There was a sex-specific effect on diastolic blood pressure (P sex×group=0·020), which was driven by a 3·9 (95 % CI 0·2, 7·5) mmHg higher diastolic blood pressure in the FO compared with the OO group among boys only (P=0·041). Our results indicate that early n-3 LCPUFA intake may reduce height in early adolescence due to a delay in pubertal maturation and increase blood pressure specifically in boys, thereby tending to counteract existing sex differences.

Effects of RYGB on energy expenditure, appetite and glycaemic control: a randomized controlled clinical trial.

OBJECTIVES: Increased energy expenditure (EE) has been proposed as an important mechanism for weight loss following Roux-en-Y gastric bypass (RYGB). However, this has never been investigated in a controlled setting independent of changes in energy balance. Similarly, only few studies have investigated the effect of RYGB on glycaemic control per se. Here, we investigated the effect of RYGB on EE, appetite, glycaemic control and specific signalling molecules compared with a control group in comparable negative energy balance. SUBJECTS/METHODS: Obese normal glucose-tolerant participants were randomized to receive RYGB after 8 (n=14) or 12 weeks (n=14). The protocol included a visit at week 0 and three visits (weeks 7, 11 and 78) where 24-h EE, appetite and blood parameters were assessed. Participants followed a low-calorie diet from weeks 0-11, with those operated at week 12 serving as a control group for those operated at week 8. RESULTS: Compared with controls, RYGB-operated participants had lower body composition-adjusted 24-h EE and basal EE 3 weeks postoperatively (both P<0.05) but EE parameters at week 78 were not different from preoperative values (week 7). Surgery changed the postprandial response of glucagon-like peptide-1 (GLP-1), peptide YY3-36 (PYY), ghrelin, cholecystokinin, fibroblast growth factor-19 and bile acids (all P<0.05). Particularly, increases in GLP-1, PYY and decreases in ghrelin were associated with decreased appetite. None of HOMA-IR (homeostasis model assessment-estimated insulin resistance), Matsuda index, the insulinogenic index, the disposition index and fasting hepatic insulin clearance were different between the groups, but RYGB operated had lower fasting glucose (P<0.05) and the postprandial glucose profile was shifted to the left (P<0.01). CONCLUSIONS: Our data do not support that EE is increased after RYGB. More likely, RYGB promotes weight loss by reducing appetite, partly mediated by changes in gastrointestinal hormone secretion. Furthermore, we found that the early changes in glycaemic control after RYGB is to a large extent mediated by caloric restriction.

No effect of high-dose atorvastatin on leukotriene B4 formation from neutrophils in patients treated with coronary bypass surgery: a randomized placebo-controlled double-blinded trial with a crossover design.

Inflammation plays a pivotal role in the pathophysiology of cardiovascular disease, (CVD) and leukotrienes may play a role in atherogenesis. Statins reduce mortality from CVD by reducing LDL cholesterol and potentially by other (pleiotropic) mechanisms. The aim of this study was to investigate if atorvastatin exerts an anti-inflammatory effect by reducing leukotriene B4 (LTB4) formation from stimulated neutrophils in patients treated with coronary artery bypass grafting. The study was a randomized, placebo-controlled, double-blinded crossover study. Patients (n=80) were allocated to 80 mg atorvastatin or placebo for 6 weeks before crossing over to the opposite treatment for another 6 weeks. There was no significant correlation between baseline LDL cholesterol levels on formation of LTB4, and atorvastatin had no effect on LTB4 formation. Hence, this study does not support any effect of atorvastatin on LTB4 formation as part of the explanation for its beneficial effect on CVD.

X-ray tomography using the full complex index of refraction.

We report on x-ray tomography using the full complex index of refraction recorded with a grating-based x-ray phase-contrast setup. Combining simultaneous absorption and phase-contrast information, the distribution of the full complex index of refraction is determined and depicted in a bivariate graph. A simple multivariable threshold segmentation can be applied offering higher accuracy than with a single-variable threshold segmentation as well as new possibilities for the partial volume analysis and edge detection. It is particularly beneficial for low-contrast systems. In this paper, this concept is demonstrated by experimental results.

The effect of low-dose marine n-3 fatty acids on the biosynthesis of pro-inflammatory 5-lipoxygenase pathway metabolites in overweight subjects: a randomized controlled trial.

INTRODUCTION: Marine n-3 polyunsaturated fatty acids (PUFA) have a variety of anti-inflammatory properties. This study evaluated the effect of n-3 PUFA in a low, but recommended cardioprotective dosage on the formation of 5-lipoxygenase pathway metabolites in overweight subjects. MATERIALS AND METHODS: Fifty subjects were randomized to 1.1g of n-3 PUFA or olive oil for 6 weeks. RESULTS: Leukotriene B(4) formation decreased by 14% in the n-3 PUFA group which proved to be significant within the group (p=0.005) but not between groups (p=0.25). The formation of 5-hydroxyeicosatetraenoic acid (5-HETE) did not differ significantly between the groups. In the n-3 PUFA group, both 5-hydroxyeicosapentaenoic (5-HEPE) acid and leukotriene B(5) increased significantly compared to the control group (p<0.001). CONCLUSION: In conclusion, we did not observe any significant net anti-inflammatory effect on the 5-lipoxygenase pathway from a daily supplement of 1.1g marine n-3 PUFA for 6 weeks.

Development of neuromodulation treatments in a large animal model--do neurosurgeons dream of electric pigs?

The Göttingen minipig has been established as a translational research animal for neurological and neurosurgical disorders. This animal has a large gyrencephalic brain suited for examination at sufficient resolution with conventional clinical scanning modalities. The large brain, further, allows use of standard neurosurgical techniques and can accommodate clinical neuromodulatory devises such as deep brain stimulation (DBS) electrodes and encapsulated cell biodelivery devices making the animal ideal for basic scientific studies on neuromodulation mechanisms and preclinical tests of new neuromodulation technology for human use. The use of the Göttingen minipig is economical and does not have the concerns of the public associated with the experimental use of primates, cats, and dogs, thus providing a cost-effective research model for translation of rodent data before clinical trials are initiated.

Effect of intensified feeding of heifer calves on growth, pubertal age, calving age, milk yield, and economics.

The objective of this study was to determine if increasing the energy and protein intake of heifer calves would affect growth rates, age at puberty, age at calving, and first lactation milk yield. A second objective was to perform an economic analysis of this feeding program using feed costs, number of nonproductive days, and milk yield data. Holstein heifer calves born at the Michigan State Dairy Cattle Teaching and Research Center were randomly assigned to 1 of 2 dietary treatments (n=40/treatment) that continued from 2 d of age until weaning at 42 d of age. The conventional diet consisted of a standard milk replacer [21.5% crude protein (CP), 21.5% fat] fed at 1.2% of body weight (BW) on a dry matter basis and starter grain (19.9% CP) to attain 0.45 kg of daily gain. The intensive diet consisted of a high-protein milk replacer (30.6% CP, 16.1% fat) fed at 2.1% of BW on a dry matter basis and starter grain (24.3% CP) to achieve 0.68 kg of daily gain. Calves were gradually weaned from milk replacer by decreasing the amount offered for 5 and 12 d before weaning for the conventional and intensive diets, respectively. All calves were completely weaned at 42 d of age and kept in hutches to monitor individual starter consumption in the early postweaning period. Starting from 8 wk of age, heifers on both treatments were fed and managed similarly for the duration of the study. Body weight and skeletal measurements were taken weekly until 8 wk of age, and once every 4 wk thereafter until calving. Calves consuming the intensive diet were heavier, taller, and wider at weaning. The difference in withers height and hip width was carried over into the early post-weaning period, but a BW difference was no longer evident by 12 wk of age. Calves fed the intensive diet were younger and lighter at the onset of puberty. Heifers fed the high-energy and protein diet were 15 d younger at conception and 14 d younger at calving than heifers fed the conventional diet. Body weight after calving, daily gain during gestation, withers height at calving, body condition score at calving, calving difficulty score, and calf BW were not different. Energy-corrected, age-uncorrected 305-d milk yield was not different, averaging 9,778 kg and 10,069 kg for heifers fed the conventional and intensive diets, respectively. However, removing genetic variation in milk using parent average values as a covariate resulted in a tendency for greater milk from heifers fed the intensive diet. Preweaning costs were higher for heifers fed the intensive diet. However, total costs measured through first lactation were not different. Intensified feeding of calves can be used to decrease age at first calving without negatively affecting milk yield or economics.

Neuromodulation in a minipig MPTP model of Parkinson disease.

Large animal neuroscience enables the use of conventional clinical brain imagers and the direct use and testing of surgical procedures and equipment from the human clinic. The greater complexity of the large animal brain additionally enables a more direct translation to human brain function in health and disease. Economical, ethical, scientific and practical issues may on the other hand hamper large animal neuroscience. Large animal neuroscience should therefore either be performed in order to examine large animal species dependent problems or to complement promising small animal basic studies by constituting an intermediate research system, bridging small animal CNS research to the human CNS. We have, accordingly, during the last ten years used the Gottingen minipig to examine neuromodulatory treatment modalities such as stem cell transplantation and deep brain stimulation directed towards Parkinson disease. This has been accomplished by the development of a MPTP-based large animal model of Parkinson disease in the Gottingen minipig and the development of stereotaxic and surgical approaches needed to manipulate the Gottingen minipig CNS. The instituted changes in the CNS can be evaluated in the live animal by brain imaging (PET and MR), cystometry, gait analysis, neurological evaluation and by post mortem examination based on histology and stereological analysis.

Intramammary infusion of leptin decreases proliferation of mammary epithelial cells in prepubertal heifers.

High energy intake and excessive body fatness impair mammogenesis in prepubertal ruminants. High energy intake and excessive fatness also increase serum leptin. Our objective was to determine if an infusion of leptin decreases proliferation of mammary epithelial cells of prepubertal heifers in vivo. Ovine leptin at 100 microg/ quarter per d with or without 10 microg of insulin-like growth factor (IGF)-I was infused via the teat canal into mammary glands of prepubertal dairy heifers; contralateral quarters were used as controls. After 7 d of treatment, bromodeoxyuridine was infused intravenously and heifers were slaughtered approximately 2 h later. Tissue from 3 regions of the mammary parenchyma was collected and immunostained for bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (Ki-67), and caspase-3. Leptin decreased the number of mammary epithelial cells in the S-phase of the cell cycle by 48% in IGF-I-treated quarters and by 19% in saline-treated quarters. Leptin did not alter the number of mammary epithelial cells within the cell cycle, as indicated by Ki-67 labeling. Caspase-3 immunostaining within the mammary parenchyma was very low in these heifers, but leptin significantly increased labeling in saline-treated quarters. Leptin enhanced SOCS-3 expression in IGF-I-treated quarters but did not alter SOCS-1 or SOCS-5 expression. We conclude that a high concentration of leptin in the bovine mammary gland reduces proliferation of mammary epithelial cells. The reduced proliferation is accompanied by an increase in SOCS-3 expression, suggesting a possible mechanism for leptin inhibition of IGF-I action. Whether leptin might be a physiological regulator of mammogenesis remains to be determined.

Modelling patient flows as an aid to decision making for critical care capacities and organisation.

Using real data from a number of hospitals, we predicted the patient flows following a capacity or organisational change. Clinically recognisable patient groups obtained through classification and regression tree analysis were used to tune a simulation model for the flow of patients in critical care units. A tuned model which accurately reflected the base case of the flow of patients was used to predict alterations in service provision in a number of scenarios which included increases in bed numbers, alterations in patients' lengths of stay, fewer delayed discharges, caring for long stay patients outside the formal intensive care unit and amalgamating small units. Where available the predictions' accuracy was checked by comparison with real hospital data collected after an actual capacity change. The model takes variability and uncertainty properly into account and it provides the necessary information for making better decisions about critical care capacity and organisation.

Effects of feeding prepubertal heifers a high-energy diet for three, six, or twelve weeks on feed intake, body growth, and fat deposition.

The objective was to determine the effects of feeding prepubertal dairy heifers a high-energy diet for a duration of 0, 3, 6, or 12 wk on feed intake, growth, and fat deposition. We also used feed composition, daily intake, and body growth data to evaluate the nutritional model of the 2001 National Research Council (NRC) Nutrient Requirements of Dairy Cattle. Holstein heifers (age = 11 wk; body weight = 107 +/- 1 kg) were assigned to 1 of 4 treatments (n = 16/treatment) designated H0, H3, H6, and H12 and fed a low-energy diet for 12, 9, 6, or 0 wk, followed by a high-energy diet for 0, 3, 6, or 12 wk, respectively. Four heifers were killed initially (11 wk of age) and 64 heifers were killed at the end of the treatment period (23 wk of age). The low-energy diet was formulated to achieve 0.6 kg of average daily gain and contained 16% crude protein, and 45% neutral detergent fiber. The high-energy diet was formulated to achieve an average daily gain of 1.2 kg and contained 18% crude protein and 23% neutral detergent fiber. Actual daily gains averaged over the 12-wk treatment period were 0.64, 0.65, 0.83, and 1.09 kg for the H0, H3, H6, and H12 groups, respectively. Body weight, withers height, hip width, carcass weight, liver weight, and perirenal fat increased in heifers fed a high-energy diet for a longer duration. In addition, percentage of fat increased and percentage of protein decreased in rib sections with a longer duration on the high-energy diet. Uterine and ovarian weights adjusted for body weight decreased when heifers were fed the high-energy diet for a longer duration. The 2001 NRC underestimated dry matter intake of the high-energy diet and overestimated dry matter intake of the low-energy diet. On the basis of actual intakes of each diet, the NRC slightly underestimated gain for the low-energy diet and overestimated gain by 40% for the high-energy diet. The likely explanation for this is that the NRC underestimated the proportion of gain that was fat in the heifers fed the high-energy diet and therefore predicted more body gain per unit of energy intake. We concluded that feeding a high-energy diet for a short duration altered body growth and fat deposition in a time-dependent, linear manner consistent with feeding a high-energy diet for a long duration.

Effects of feeding prepubertal heifers a high-energy diet for three, six, or twelve weeks on mammary growth and composition.

The experimental objective was to determine the effects of feeding prepubertal dairy heifers a high-energy diet for 3, 6, or 12 wk on mammary growth and composition. Holstein heifers (age = 11 wk; body weight = 107 +/- 1 kg) were assigned to 1 of 4 treatments (n = 16/ treatment). The treatment period lasted 12 wk and treatments were H0 (low-energy diet fed for 12 wk, with no weeks on the high-energy diet); H3 (low-energy diet fed for 9 wk, followed by the high-energy diet for 3 wk); H6 (low-energy diet fed for 6 wk, followed by the high-energy diet for 6 wk); and H12 (high-energy diet for all 12 wk). The low- and high-energy diets were formulated to achieve 0.6 and 1.2 kg of average daily gain, respectively. Heifers were slaughtered at 23 wk of age and mammary tissue was collected. A longer duration of feeding the high-energy diet increased total mass of the mammary gland, extraparenchymal fat, and intraparenchymal fat, but did not alter the mass of fat-free parenchymal tissue. When adjusted for carcass weight to reflect differences in physical maturity, the mass of fat-free parenchymal tissue decreased in a linear fashion with a longer duration on the high-energy diet. Total masses of mammary parenchymal DNA and RNA were not different. However, after adjustment for carcass weight, the masses of DNA and RNA decreased as heifers were fed the high-energy diet for a longer duration. The percentages of epithelium, stroma, and lumen, the number of epithelial structures, and the developmental scores of mammary parenchymal tissue were not different among treatments. However, the percentage of proliferating epithelial cells in the terminal ductal units, as indicated by Ki-67 labeling, decreased as heifers were fed the high-energy diet for a longer duration. We concluded that feeding prepubertal heifers a high-energy diet for a longer duration resulted in a linear decrease in both the percentage of mammary epithelial cells that were proliferating and in the mass of fat-free mammary parenchyma per unit of carcass. High-energy feeding hastens puberty and, in this study, decreased mammary epithelial cell proliferation in areas of active ductal expansion. These data are consistent with the idea that feeding heifers a high-energy diet will reduce mammary parenchymal mass at puberty.

Chronic subthalamic high-frequency deep brain stimulation in Parkinson's disease--a histopathological study.

This study describes the pathological findings in the brain of a patient with Parkinson's disease (PD) treated with bilateral subthalamic high-frequency deep brain stimulation (STN DBS) for 29 months prior to death. After routine neuropathological examination, tissue blocks containing the electrode tracts, the subthalamic nucleus (STN), the substantia nigra and the pre-frontal cortex were paraffin embedded and cut into 5-microm-thick serial sections and stained with several conventional staining methods and immunohistochemistry. Bilateral nigral depigmentation, cell loss and Lewy body formation confirmed the diagnosis of PD. Microscopic evaluation furthermore confirmed the location of the electrodes in the STN. The electrode tracts were surrounded by a 150-microm-wide glial fibrillary acidic protein (GFAP)-positive capsule consisting of a thin collagen layer lining the lumen of the tract, whilst an area with few cells and axons constituted the capsule wall towards the surrounding normal brain tissue. The brain tissue appeared normal outside the capsule boundaries with no difference in areas of stimulation compared with areas of no stimulation. Our results correspond with previous studies performed after fewer months of STN DBS and indicate mild histopathological changes in the vicinity of the electrode tract, appearing to result from the electrode placement and not from the electrical stimulation.

Short communication: intramammary infusion of IGF-I increases bromodeoxyuridine labeling in mammary epithelial cells of prepubertal heifers.

When dairy heifers are fed to gain more than 900 g of body weight/d, they have less mammary parenchymal DNA at puberty but more insulin-like growth factor-I (IGF-I) in serum. This negative relationship between serum IGF-I concentration and mammary epithelial cell proliferation is in disagreement with the extensively reported role of IGF-I as a stimulator of mammary epithelial cell proliferation. Despite the large body of evidence suggesting that an increase in IGF-I concentration should lead to an increase in mammary epithelial cell proliferation of prepubertal heifers, it had not been previously tested. Our objective was to determine if intramammary infusions of IGF-I would stimulate mammogenesis in prepubertal heifers in vivo. After 7 d of treatment, bromodeoxyuridine was infused intravenously and heifers were slaughtered 3 h later. Samples from 3 regions of the mammary parenchyma were collected, fixed, sliced, and incubated with bromodeoxyuridine monoclonal antibody to identify cells in the S-phase of the cell cycle. Intramammary infusion of IGF-I increased the percentage of epithelial cells in the S-phase by 52% (6.4 vs. 4.2%, +/- 0.3%). Proliferation was similar in all 3 parenchymal regions, and the response to IGF-I was similar in each region. We conclude that local IGF-I increases proliferation of mammary parenchymal epithelial cells in prepubertal heifers.

SorCS3 does not require propeptide cleavage to bind nerve growth factor.

The functional properties of the Vps10p-domain receptor SorCS3 are undescribed. Here, we examine its processing and sorting in cellular transfectants, and analyze the binding of potential ligands to the purified receptor. We show that SorCS3 is synthesized as a proprotein and converted to its mature form by N-terminal propeptide cleavage in distal Golgi compartments. The propeptide is not a requirement for normal processing of the receptor and does not prevent ligands from binding to the SorCS3 precursor form. Expression of wt and chimeric receptors further suggests that SorCS3 predominates on the plasma membrane, exhibits slow internalization and does not engage in intracellular trafficking. SorCS3 emerges as a new neurotrophin binding Vps10p-domain receptor functionally distinct from its relatives Sortilin and SorLA.

Effect of increasing energy and protein intake on body growth and carcass composition of heifer calves.

The objective was to determine whether increased energy and protein intake between 2 and 14 wk of age would increase growth rates of heifer calves without fattening. At 2 wk of age, Holstein heifer calves were assigned to 1 of 4 treatments in a 2 x 2 factorial arrangement with 2 levels of protein and energy intake (moderate [M]; high [H]) in period 1 (2 to 8 wk of age) by 2 levels of protein and energy intake (low [L]; high [H]) in period 2 (8 to 14 wk of age) to produce similar initial BW for all 4 treatments. Treatments were ML, MH, HL, and HH, indicating moderate or high energy and protein intake during the first period and low or high intake during the second period. The M diet consisted of a standard milk replacer (21.3% CP, 21.3% fat) fed at 1.1% of BW on a DM basis and a 16.5% CP grain mix fed at restricted intake to promote 400 g of average daily gain (ADG), whereas the L diet consisted only of the grain mix. The H diet consisted of a high-protein milk replacer (30.3% CP, 15.9% fat) fed at 2% of BW on a DM basis and a 21.3% CP grain mix available ad libitum. Calves were weaned gradually from milk replacer by 7 wk and slaughtered at 8 (n = 11) or 14 wk of age (n = 41). In periods 1 and 2, ADG and the gain:feed ratio were greater for calves fed the H diet. Calves fed the H diet were taller after both periods 1 and 2. No difference was observed in carcass composition at 8 wk, but at 14 wk calves fed MH and HH had less water and more fat than calves fed ML and HL. Plasma IGF-I concentrations were greatest for calves fed the H diet during either period. Plasma leptin concentrations were increased in calves fed the H diet during period 1 from 4 to 6 wk of age. Increasing energy and protein intake from 2 to 8 wk and 8 to 14 wk of age increased BW, withers height, and gain:feed ratio. Calves fed the H diet from 8 to 14 wk of age had more body fat than calves fed the L diet. Increased energy and protein intake can increase the rate of body growth of heifer calves and potentially reduce rearing costs.

Effect of increasing energy and protein intake on mammary development in heifer calves.

The objective of this study was to determine if increased energy and protein intake from 2 to 14 wk of age would affect mammary development in heifer calves. At 2 wk of age, Holstein heifer calves were assigned to 1 of 4 treatments in a 2 x 2 factorial arrangement with 2 levels of protein and energy intake (moderate, M; high, H) in period 1 (2 to 8 wk of age) and 2 levels of protein and energy intake (low, L; high, H) in period 2 (8 to 14 wk of age), so that mean initial body weights were approximately equal for all 4 treatments (ML, MH, HL, and HH). The M diet in period 1 consisted of a standard milk replacer (21.3% CP, 21.3% fat) fed at 1.1% of BW on a DM basis and a 16.5% CP grain mix fed at restricted intake to promote 400 g of daily gain, whereas the L diet in period 2 consisted only of the grain mix. The H diet in period 1 consisted of a high-protein milk replacer (30.3% CP, 15.9% fat) fed at 2.0% of body weight on a DM basis and a 21.3% CP grain mix available ad libitum. In period 2, the H diet consisted of just the 21.3% grain mix. Calves were gradually weaned from milk replacer by 7 wk and slaughtered at 8 (n = 11) or 14 wk of age (n = 41). Parenchyma from the distal region, midgland, and proximal region relative to the teat from one half of the udder was collected, fixed, and embedded in paraffin. The other half of the gland was used to determine parenchymal mass, protein, fat, DNA, RNA, and extraparenchymal mass. Total parenchymal tissue, parenchymal DNA, parenchymal RNA, and concentrations of DNA and RNA were higher for calves on the H diet during period 1, but were not affected by diet during period 2. Parenchymal fat percentage was increased by the H diet during period 2. The H diet increased extraparenchymal fat during both periods. The area of parenchyma occupied by epithelium was not affected by treatment, but at the end of period 2, the percentage of proliferating epithelial cells as indicated by Ki67, an marker of cell proliferation, expression was greater for calves on the M diet in period 1 compared with calves on the H diet in period 1. Diets did not influence parenchymal protein percentage or the ratio of RNA to DNA. Higher energy and protein intake from 2 to 8 wk of age increased parenchymal mass and parenchymal DNA and RNA in mammary glands of heifer calves without increasing deposition of parenchymal fat. Diet also influenced histological development of mammary parenchyma and subsequent proliferation of ductal epithelial cells. Implications of these effects for future milk production potential are unknown.

Routine X-ray control of upper central venous lines: Is it necessary?

BACKGROUND: Insertion of central venous catheters (CVCs) is a procedure associated with a varying risk of complications, depending on the setting and the skill of the clinician who undertakes the procedure. The aim of this study was to monitor the complication rate of CVC insertion and evaluate the value of routine chest X-ray control. METHODS: Anesthesiologists at eight hospitals filled in a questionnaire immediately after insertion of a CVC. The post-procedural clinical evaluation, including expected complications, was compared to actual radiological findings. Chest X-ray was ordered by the anesthesiologist, and described by staff radiologists. RESULTS: The clinicians had from 2 months to 30 years of experience as anesthesiologists, and trainees inserted 34% and specialists 66% of the catheters, using landmark techniques. Over a period of 2 months, 473 CVC-insertion procedures were included in the investigation. Two patients (0.4%) had a pneumothorax: one was among the 11 cases in which the clinician suspected complications after the procedure, and another was found in a high-risk patient 13 h after CVC insertion. Both patients were treated successfully with chest tubes. The favorite approach was right vena jugularis interna with 324 (69%) catheters; of these patients one had a pneumothorax, catheter-tip placement was correctly predicted in 317 (97%), and no catheters were repositioned. CONCLUSION: In the hands of trained clinicians, insertion of CVCs is a safe procedure. We found no value of routine X-ray control and omission of routine chest X-ray must be considered.