Technical note: Nitrogen isotopic fractionation can be used to predict nitrogen-use efficiency in dairy cows fed temperate pasture.

The objective of this study was to investigate the relationship between nitrogen isotopic fractionation (δ(15)N) and nitrogen-use efficiency (milk nitrogen/nitrogen intake; NUE) in pasture-fed dairy cows supplemented with increasing levels of urea to mimic high rumen degradable protein pastures in spring. Fifteen cows were randomly assigned to freshly cut pasture and either supplemented with 0, 250, or 336 g urea/d. Feed, milk, and plasma were analyzed for δ(15)N, milk and plasma for urea nitrogen concentration, and plasma for ammonia concentration. Treatment effects were tested using ANOVA and relationships between variables were established by linear regression. Lower dry matter intake (P = 0.002) and milk yield (P = 0.002) occurred with the highest urea supplementation (336 g urea/d) compared with the other two treatments. There was a strong linear relationship between milk δ(15)N - feed δ(15)N and NUE: [NUE (%) = 58.9 - 10.17 × milk δ(15)N - feed δ(15)N (‰) (r(2) = 0.83, P < 0.001, SE = 1.67)] and between plasma δ(15)N - feed δ(15)N and NUE: [NUE (%) = 52.4 - 8.61 × plasma δ(15)N - feed δ(15)N (‰) (r(2) = 0.85, P < 0.001, SE = 1.56)] . This study confirmed the potential use of δ(15)N to predict NUE in cows consuming different levels of rumen degradable protein.

Timing of supplementation alters grazing behavior and milk production response in dairy cows.

Offering feed supplements to grazing dairy cows results in substitution of pasture; however, previous data indicate that the time at which concentrate supplements are offered might affect the level of substitution. These data indicated that cows grazed more intensely presunset, regardless of the amount of supplement offered. It was, therefore, hypothesized that substitution rate would be less, and response to supplement greater if cows received their supplement at the p.m. rather than the a.m. milking. Forty-eight multiparous, nonpregnant, Holstein-Friesian cows, approximately 60 d in milk, were randomly allocated to 1 of 3 treatments in an incomplete crossover arrangement. Treatments were pasture only, pasture + 3 kg of concentrate supplement dry matter (DM) offered during the a.m. milking (AM-SUP), and pasture + 3 kg of concentrate supplement DM offered during the p.m. milking (PM-SUP). Time spent grazing and calculated pasture DM intake did not differ between the AM-SUP and PM-SUP cows. However, a tendency (0.18 kg of milk/kg of concentrate DM) was observed for an increased marginal milk response (kg of milk/kg of DM supplement) for the AM-SUP cows when compared with PM-SUP cows. Irrespective of when supplements were offered, supplementation reduced total grazing time by a similar amount, and the reduction in time spent grazing was evident throughout the day. Cows in the PM-SUP group ruminated for longer and cows in the AM-SUP group spent more time idle compared with the pasture only groups. Cows in the AM-SUP group grazed for less time during the major a.m. grazing bout following a.m. milking compared with PM-SUP cows; in comparison, the major p.m. grazing bout following p.m. milking was unaffected by supplementation. The results indicated possible improvements in marginal milk response to supplements from altering the timing of delivery.

Efficacy of topical treatments for cutaneous warts: a meta-analysis and pooled analysis of randomized controlled trials.

Many topical treatments for cutaneous warts exist and previous reviews of trials did not follow intention-to-treat (ITT) principles for analysis. We aimed to perform a meta-analysis and pooled analysis of randomized controlled trials (RCTs) of topical treatment for cutaneous warts using ITT principles. Systematic electronic searches (Cochrane library, Medline, Embase, Clinical trial registers) were conducted in May 2009. Included trials reported completed cure of warts and data were extracted from these trials. We performed random-effects meta-analysis and assessed heterogeneity using the I(2) statistic and conducted a pooled analysis of each treatment. We found 77 relevant studies of which the majority were of low methodological quality. Salicylic acid (SA) was superior to placebo with a risk ratio (RR) for cure of 1·60 [95% confidence interval (CI) 1·15-2·24]. Cryotherapy was not statistically better than placebo, RR 0·89 (95% CI 0·27-2·92), but aggressive cryotherapy was significantly better than gentle cryotherapy with a RR of 2·06 (95% 1·20-3·52). Combined therapy of SA and cryotherapy had a higher cure rate than either SA or cryotherapy alone. The results of the pooled analysis found a cure rate of 23% (5-73%) in placebo trials, 52% (0-87%) in SA trials, 49% (0-69%) in cryotherapy trials, 54% (45-75%) in aggressive cryotherapy trials and 58% (38-78%) in the combined cryotherapy and SA trials. Aside from the use of SA and aggressive cryotherapy there is insufficient evidence from RCTs to support the use of other therapies. Higher quality evidence is needed to evaluate other therapies.

Assessment of the production of analgesia induced by application of a rubber ring or local anaesthetic to the antler pedicle of yearling stags.

AIMS: To compare two methods of applying rubber rings to the pedicles of yearling stags to induce analgesia in the antler prior to removal. To compare the application of a rubber ring with that of a lignocaine ring block of the antler pedicle on the efficacy and time course of the analgesia produced in yearling stags. METHODS: Rubber rings were applied to the pedicles of 36 yearling stags that required velvet antler removal. The standard method, a doubled-over ring expanded and lowered down from the distal end of the antler and released midway down the pedicle, was compared with a cable-tie method on the other pedicle, where a ring was pulled around the pedicle by an electrical cable tie threaded through the ring. Brief electrical stimulation (train-of-four mode) was applied proximal and distal to the ring before, and at regular intervals for 1 hour after, application of the ring to a level that produced an auriculopalpebral reflex response. In a second experiment, each pair of antlers per yearling stag (n=36) was allocated to one of three pairs of treatments, viz no treatment (control) and the cable-tie method as described above, control and local anaesthesia (a ring block of 2 ml 2% lignocaine per cm pedicle circumference), or the cable-tie method and local anaesthesia. Electrical stimulation (tetanic mode) was applied to each antler approximately 25 mm distal to the pedicle/antler junction before, and at intervals up to 1 hour after, application of treatments at a level required to produce a head/neck avoidance behavioural response. In a third experiment, the two electrical stimulation protocols used above were directly compared by measuring the response of stags (n=8) to one protocol on each pedicle/antler prior to, and at intervals for 1 hour after, application of a rubber ring. At the end of each treatment in all three experiments, analgesia of the antler was established as a nil behavioural response of the stag to a saw cut to the antler (the 'nick test'). RESULTS: For both methods of application of a ring the minimum electrical stimulation required distal to the ring to elicit a reflex response increased from around 16 to 55 mA by 60 minutes. In contrast, the electrical stimulation required proximal to the ring remained low (approximately 17.0 mA) throughout. No stag subjected to either of the methods of application responded to the nick test 60 minutes after application of the ring. The electrical stimulation required to produce a behavioural response increased very rapidly in stags treated with local anaesthetic and at a slower rate in those treated with the cable-tie method but showed no significant increase in control stags. After 4 and 30 minutes, for local anaesthesia and the cable-tie method, respectively, 95% of stags were not responding to 80 mA. A significantly greater proportion of stags with antlers treated with local anaesthetic and the cable-tie method did not respond to the nick test than controls, and there was no significant difference in the frequency of the response between stags with treated antlers. The minimum current required to produce a response proximal to a rubber ring was slightly higher on average for train-of-four electrical stimulus (mean 18.1 (SD 2.6) mA) than for the tetanic mode (mean 11.9 (SD 2.5) mA). The increase in minimum current required to produce the respective response to stimulation distal to the ring was similar for both methods, although the maximum predicted value (67.4 mA) was lower for train-of-four than for the tetanic mode (84.5 mA). No stag responded to the nick test > or = 60 minutes after application of the ring. CONCLUSIONS: The cable-tie method was no different from the standard method as a procedure for producing analgesia in the antlers of yearling stags and should be accepted as an appropriate procedure for applying analgesic rings to yearling stags. The analgesia produced in the antlers of yearling stags by rubber rings applied by the cable-tie method to the pedicle was similar to that of a lignocaine ring block, but the time course for the development of analgesia was markedly different. Given that a lignocaine ring block is accepted as an adequate method of pain relief for antler removal, the application of rubber rings followed by a period of > or = 30 minutes after application can be advocated as a viable alternative for pain relief.

Interactive effects of nitrogen deposition and fire on plant and soil chemistry in an alpine heathland.

The response of alpine heathland vegetation and soil chemistry to N additions of 0, 10, 20 and 50 kg N ha(-1) year(-1) in combination with simulated accidental fire (+/-) was monitored over a 5-year period. N addition caused rapid and significant increases in plant tissue N content and N:P and N:K of Calluna vulgaris, suggesting increasing phosphorus and potassium limitation of growth. Soil C:N declined significantly with N addition, indicating N saturation and increasing likelihood of N leakage. Fire further decreased soil C:N and reduced potential for sequestration of additional N. This study shows that alpine heathlands, which occupy the headwaters of many rivers, have limited potential to retain deposited N and may rapidly become N saturated, leaking N into downstream communities and surface waters.

Losing touch with the healing art: dermatology and the decline of pastoral doctoring.

Technological advance in society and medicine has brought tremendous improvements and convenience but also a degree of depersonalization. The personal and pastoral aspects of medical practice, which are probably more important in helping patients toward health than we realize, are becoming increasingly stifled by health care systems which are increasingly "scientific," technological, and "efficient." Clinical practice in dermatology requires pastoral as well as technical skills, art as well as science, and yet the balance of current medical culture increasingly favors and encourages "science" over "art." In dermatology, this bias is evident in a reductionist focus of research, the move towards evidence-based medicine and the emergence of teledermatology. Although all these developments are extremely important and valuable, their effect on the doctor-patient relationship needs to be considered carefully. Increasingly rapid scientific advance is paradoxically providing diminishing returns for patients and the healing art is still very much in demand.

Expression of skin-derived antileukoproteinase (SKALP) in reconstructed human epidermis and its value as a marker for skin irritation.

For the investigation of the skin irritancy potential of chemicals in an in vitro model, it is necessary to have sensitive end-points that predict the effects on native human skin. Our aim was to investigate whether the induction of the proteinase inhibitor SKALP in reconstructed epidermis can be used as a marker. The influence of culture conditions and the effect of topical application of sodium lauryl sulfate and oleic acid on SKALP expression were evaluated using immunohistochemistry and Northern blotting. SKALP expression was induced by serum, epidermal growth factor and fibroblasts. In the presence of retinoic acid and 1,25-dihydroxyvitamin D3 SKALP expression was inhibited, whereas supplementation with ascorbic acid and a-tocopherol had no effect. Tape-stripping of excised skin and topical treatment with sodium lauryl sulfate induced SKALP protein expression. Application of sodium lauryl sulfate and oleic acid on reconstructed epidermis also induced SKALP at the protein level but no significant effects could be demonstrated at mRNA levels. In conclusion, SKALP expression, which was increased upon application of sodium lauryl sulfate and oleic acid, can be used as an in vitro end-point for skin irritancy, irrespective of the modifying effects of culture conditions.

Regulation of keratinocyte proliferation and differentiation by all-trans-retinoic acid, 9-cis-retinoic acid and 1,25-dihydroxy vitamin D3.

We studied the effect of all-trans retinoic acid (all-trans-RA), 9-cis-retinoic acid (9-cis-RA) and 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) on proliferation and differentiation of human keratinocytes cultured in a submerged culture system for up to 5 weeks and evaluated changes in cell morphology and in the expression of proliferation- and terminal differentiation-related genes on both the mRNA and the protein levels. Under control culture conditions, the expression of small proline-rich proteins (SPRR1 and SPRR2), involucrin, Ki67 and c-jun reached a maximum after 2 weeks in culture (1 week postconfluence) and then decreased as the tissue architecture of the cultures deteriorated. Upon simultaneous treatment with both retinoids and 1,25(OH)2D3 a culture was generated that remained stable for 4 weeks with at least eight living cell layers. Furthermore, this culture showed a pattern of SPRR2 and involucrin expression which closely resembled that of native epidermis, a maintained Ki67 expression and a strongly induced c-jun expression. Treatment with 1,25(OH)2D3 alone inhibited cell proliferation and stimulated cell differentiation resulting in acceleration of the differentiated phenotype and was accompanied by inhibition of c-jun and Ki67 expression and also, surprisingly by inhibition of SPRR1, SPRR2 and involucrin expression. In contrast, treatment with all-trans-RA and/or 9-cis-RA induced a more proliferative phenotype with a prolonged lifespan as compared to control cultures. SPRR1 was weakly repressed, SPRR2 was strongly repressed, a delayed induction of involucrin occurred, and c-jun and Ki67 expression were maintained. These results show that modulation of the composition of the medium by the addition of various vitamins results in changes in the balance between keratinocyte proliferation and differentiation which correspond to changes in the expression of proliferation and differentiation markers and prolongation of the culture lifespan.

High-voltage pulsed galvanic stimulation: effects of frequency of current on blood flow in the human calf muscle.

1. Twelve healthy subjects received high-voltage pulsed galvanic stimulation (115-475 V d.c.) delivered in separate treatments of 2, 32 and 128 pulses/s for 10 min at the subject's maximum tolerable voltage while calf muscle blood flow was measured by non-invasive Whitney strain-gauge venous occlusion plethysmography. 2. The high-voltage pulsed galvanic stimulation was administered with negative polarity by an intermittent mode of 30 s on, 30 s off. Measurements of calf muscle blood flow were made during each 30 s period when the stimulus was off. The effect of one 30 s maximum isometric contraction of the calf muscles on blood flow was used as a standard for evaluating the effectiveness of high-voltage pulsed galvanic stimulation on calf muscle blood flow. 3. Significant (paired t-tests; P less than 0.05) increases in calf muscle blood flow over the preceding baseline levels occurred for the isometric contraction (322%) and for frequencies of 2 pulses/s (33.5%) and 128 pulses/s (13.36%), but not for a frequency of 32 pulses at which calf muscle blood flow increased in only six of 12 subjects. The mean increases in calf muscle blood flow at 2 and 128 pulses/s represented 11.63% and 4.0%, respectively, of that resulting from the isometric contraction. 4. A clear positive correlation between voltage level and the magnitude of increase in calf muscle blood flow was demonstrated but differed for each frequency used.(ABSTRACT TRUNCATED AT 250 WORDS)

Dermatomyositis: correlative MR imaging and P-31 MR spectroscopy for quantitative characterization of inflammatory disease.

Magnetic resonance (MR) imaging and phosphorus-31 MR spectroscopy were used to examine four patients with dermatomyositis and five control subjects. T2-weighted images of the thigh muscles of patients showed increased signal intensity, with focal and inhomogeneous involvement predominantly in the vastus lateralis and secondarily in the vastus intermedius and vastus medialis. T1 and T2 values of the vastus lateralis in patients were significantly higher than those of the control subjects. T1 values of the rectus femoris and biceps femoris with more generalized inflammation were moderately elevated but still significantly higher than those of the control subjects. P-31 MR spectra of the quadriceps muscles were obtained during rest, during exercise at two graded levels, and in recovery. Concentrations of adenosine triphosphate and phosphocreatine (PCr) in the diseased muscles were 30% below normal values, and the inorganic phosphate/PCr ratios were increased in the patients' muscles at rest and throughout exercise. The T1 and T2 values as well as the P-31 metabolite data correlated with symptoms and clinical assessment.

Ethylenediaminetetra(methylenephosphonic) acid (EDTPO) as a therapeutic chelating agent.

Ethylenediaminetetra(methylenephosphonic) acid (EDTPO), when administered as its calcium salt, is an effective antidote for acute intoxication by a number of metal ions. Significant antidotal action was found for the following cations: Cd2+, Ni2+, Zn2+, Pb2+, Be2+ and UO2+(2). Because EDTPO is capable of chelating more than one calcium ion, better results were obtained when the Ca2EDTPO complex was administered.

A comparison of diethyldithiocarbamate and EDTA as antidotes for acute cadmium intoxication.

For mice which have been given the cadmium equivalent of CdCl2 X 2 1/2H2O at a level of 10 mg/kg, diethyldithiocarbamate (DDTC) administration at 500 mg/kg leads to a higher survival rate than is found with Na2CaEDTA under identical conditions. This occurs when the interval between administration of the cadmium salt and the antidote is either one or two hours. The surviving animals, however, are found to have appreciable levels of cadmium in their brain, liver and kidney when they were treated with DDTC, though their behavior appeared to be normal. The use of 50 mg/kg of DDTC after 2 hr in such cadmium poisoned mice also leads to a higher survival rate and reduced amounts of cadmium retained in the brain, liver and kidney. Unlike the other chelating agents which have been reported as useful in acute cadmium intoxication, DDTC appears to act by forming a lipid soluble complex which is largely immobilized in lipid containing tissues of the animal's body.