Short communication: Effects of different blood buffers administered in electrolyte solution to grain-fed veal calves experiencing diarrhea.

Calf diarrhea can commonly lead to dehydration and metabolic acidosis due to the loss of fluid and electrolytes. The objective of this randomized clinical trial was to examine differences between treating male dairy calves experiencing diarrhea with either a basic bicarbonate electrolyte powder (BBP) composed of sodium bicarbonate (50.7 mmol/L); a mixed buffer powder (MBP) including sodium bicarbonate (33.8 mmol/L), sodium citrate (8.4 mmol/L), sodium acetate (6.3 mmol/L), and potassium citrate (1.9 mmol/L); or a liquid electrolyte (HAL) composed of sodium acetate (50.1 mmol/L). All 3 electrolyte solutions were standardized to provide 50 mmol/L blood buffers and a similarly strong ion difference (74.4, 74.9, and 82.6 mEq/L for BBP, MBP, and HAL, respectively). Holstein male calves (n = 80) were sourced from auction barns or local farms and delivered in 1 batch to the research facility. Calves were housed in individual pens and fed a 24% crude protein and 17% fat calf milk replacer (CMR) twice daily. Starter grain and water were offered ad libitum. Calves were randomly enrolled in 1 of the 3 treatments when experiencing either 2 consecutive days of a fecal score of 2 (runny, spreads easily) or 1 d with a fecal score of 3 (liquid devoid of solid material). Calves were blocked by the different enrollment criteria. The respective electrolyte solution was administered via esophageal tube 1 h after feeding CMR until the fecal score returned to 0 (normal consistency) or 1 (semiformed or pasty). Blood gas measurements were taken at 1, 8, and 24 h post the initial electrolyte feeding, and weight was measured at 1, 2, 7, 14, and 28 d postenrollment. Mixed repeated measure linear regression models were built to assess the effect that the electrolyte solutions had on the blood gas measurements and body weight. A total of 45 calves were enrolled in the trial with 14, 16, and 15 calves randomly assigned to the MBP, HAL, and BBP groups, respectively. As compared with BBP, MBP increased blood CO2 at 8 and 24 h, increased bicarbonate at 24 h, increased base excess at 8 and 24 h, and increased anion gap at 24 h. Calves in the BBP and HAL groups noted more severe eye recession when compared with the MBP group. Average daily gain did not differ between treatments at any time point. Although a severe dehydration challenge was not present, which should be considered a limitation of the study, MBP improved the acid-base status of calves compared with BBP, whereas HAL performed similarly to MBP.

Short communication: Effects of porcine plasma or combined sodium butyrate and Bacillus subtilis on growth and health of grain-fed veal calves.

The objective of this study was to evaluate the effects of incorporating 2 commonly used additives or spray-dried porcine plasma in calf milk replacer (CMR) on calf performance and health. Male Holstein calves (n = 158) transported from auction barns and local dairy farms were randomly assigned to receive 1 of 3 decoquinate-containing CMR for the first 49 d of the experiment: all milk protein and no additives (CONT); 15% of crude protein (CP) replaced with spray-dried porcine plasma, no additives (PLM); or all milk protein and an added combination of sodium butyrate (rate 1.4 kg of butyric acid/Mt) and Bacillus subtilis (1.28 million cfu/g of feed; BB). All milk replacers were formulated to contain 26% CP and 17% fat, 2.4% Lys, and 0.8% Met, and were bucket-fed at daily feeding rates of 520 g during wk 1 and 2, 650 g during wk 3, and 900 g during wk 4 and 5, in a total of 4, 5, and 6 L of solution, respectively. Calves were offered texturized calf starter (18% CP) upon arrival until wk 3 and transitioned to a corn and pellet ration with 2% straw (18.1% CP). No prophylactic administration of antibiotics occurred. All calves were gradually weaned over a 2-wk period. Calves were individually housed until weaned and then housed in groups of 5 in a mechanically ventilated facility in southwestern Ontario, Canada. Fecal scores, treatments administered (antibiotic or supportive therapy), and mortalities were recorded daily. Body weight was measured using a digital scale at arrival and at 14, 49, 56, and 78 d after arrival. No differences were found among the groups with respect to growth, feed efficiency, or incidence of diarrhea or respiratory infection treatment. Calves supplemented with BB had a greater hazard of mortality over the growing period compared with CONT. An interaction was found between the BB group and the level of total serum protein, with the BB group having a lower proportion of days with a fecal score of 3 when the calves had a higher total serum protein level. Calves fed PLM had a lower proportion of d with a fecal score of 3 relative to CONT but no difference in the proportion of d with a fecal score of 2 or higher. This study found that the addition of spray-dried plasma in CMR reduced diarrhea severity; however, supplementing BB was associated with a higher hazard of calf mortality and had a varying response on fecal score.

Effect of porcine plasma on growth and health of Holstein calves.

The objective of this trial was to compare the health and performance of calves provided high feeding rates of a whey-based all-milk-protein calf milk replacer (MR) with those fed an MR containing either 5% or 10% porcine plasma, which replaced, respectively, either 15% or 30% of the whey-based proteins in the MR formula. A total of 320 male Holstein calves weighing a mean (± SD) of 47.8 ± 4.1 kg were sourced from local dairy farms, auction facilities, and local order buyers. Calves arrived at the research facility in 4 batches of 80 animals each and were randomly assigned to 1 of 3 groups: (1) MR composed of whey-based milk proteins (control group); (2) whey replacement of 5% spray-dried porcine plasma (replacing 15% of protein); or (3) whey replacement of 10% spray-dried porcine plasma (replacing 30% of protein). Calves were housed in individual pens for the first 56 d of the experiment and offered, twice daily, a 26% crude protein (CP), 20% fat MR standardized using synthetic amino acids to 2.4% lysine, 0.8% methionine, and 1.6% threonine. Amounts of MR offered from wk 1 to 8 were 0.65, 0.78, 0.91, 1.04, 1.04, 0.78, 0.52, and 0.325 kg/d, respectively. Calves were also offered a 20% CP texturized calf starter from d 0 to 56 and then transitioned over 7 d (d 56-62) of a 50% calf starter and 50% corn and pellet ration with 2% straw to a corn and pellet ration with 2% straw (18.1% CP) for the remainder of the experiment (d 63-77). Calves were individually weighed upon arrival, weekly through d 56, and at d 77. Grain was fed ad libitum, and remaining grain was weighed weekly to determine weekly consumption. Remaining grain was discarded and was replaced with fresh grain that was weighed and recorded. All milk was offered individually via bucket twice daily, and refusals were recorded following milk feeding by weighing back the remaining unconsumed milk solution. Calves were health scored twice daily, and any medical treatments or mortality were recorded. Time to mortality and medical treatments were analyzed using survival analysis, health scoring data were analyzed using a generalized linear model, and growth was evaluated using a mixed repeated-measures linear regression model. No differences in mortality or incidence of diarrhea were noted between groups. Although there was a high incidence of respiratory disease (65%), no differences were found between groups. Over the entire experimental period, calves gained 67.0 ± 14.9 kg; however, no differences in growth among groups were noted, with the exception that, on d 77, BW was greater for calves in the control group (115.8 ± 15.5 kg) compared with those fed a MR with 5% porcine plasma (113.4 ± 17.8 kg). No differences were found between groups with respect to feed conversion. In this study, an MR composed of either 5% or 10% spray-dried porcine plasma performed comparably to a whey protein-based MR.

A survey of enteric bacteria and protozoans in fresh bovine faeces on New Zealand dairy farms.

AIMS: To determine the counts and/or prevalence in fresh bovine faeces of Escherichia coli, enterococci, Campylobacter, Salmonella, shiga toxin-producing E. coli (STEC), Giardia and Cryptosporidium, as inputs to numerical models designed to estimate microbial loadings on pasture grazed by cattle in New Zealand. METHODS AND RESULTS: In each season over one year, samples of freshly deposited bovine faeces were collected from four New Zealand dairy farms (n = 155), and enumerated for E. coli, enterococci, Campylobacter, Giardia and Cryptosporidium. They were also tested for the presence of Salmonella and STEC. The overall median bacterial counts (g(-1) wet weight) were E. coli- 5.9 x 10(6); enterococci - 1.3 x 10(4); Campylobacter- 3.9 x 10(5). All counts were highly variable within and between samplings, and few seasonal or regional patterns emerged. However, mean Campylobacter counts were consistently higher in spring. No Salmonella spp. was detected, and only two samples were positive for STEC. Cryptosporidium and Giardia were isolated from 5.2% and 4.5% of the samples, respectively, yielding low numbers of (oo)cysts (1-25 g(-1) and 1-17 g(-1), respectively). CONCLUSIONS: Fresh bovine faeces are a significant source of E. coli, enterococci and Campylobacter on New Zealand pastures, although numbers are likely to vary markedly between faecal samples. SIGNIFICANCE AND IMPACT OF THE STUDY: The study provides the first significant set of indicator and pathogen counts for one of the largest sources of faecal contamination of natural waters in New Zealand, and will be used to model these inputs.

A dominant activating mutation in the effector region of RAS abolishes IRA2 sensitivity.

Previously described mutations in RAS genes that cause a dominant activated phenotype affect the intrinsic biochemical properties of RAS proteins, either decreasing the intrinsic GTPase or reducing the affinity for guanine nucleotides. In this report, we describe a novel activating mutation in the RAS2 gene of Saccharomyces cerevisiae that does not alter intrinsic biochemical properties of the mutant RAS2 protein. Rather, this mutation, RAS2-P41S (proline 41 to serine), which lies in the effector region of RAS, is shown to abolish the ability of the IRA2 protein to stimulate the GTPase activity of the mutant RAS protein. This mutation also modestly reduced the ability of the mutant protein to stimulate the target adenylate cyclase in an in vitro assay, although in vivo the phenotypes it induced suggest that it retains potency in stimulation of adenylate cyclase. Our results demonstrate that although the effector region of RAS appears to be important for interaction with both target effector and negative regulators of RAS, it is possible to eliminate negative regulator responsiveness and retain potency in effector stimulation.

Attention deficit disorder ('minimal brain dysfunction') in adults. A replication study of diagnosis and drug treatment.

This study replicated an earlier one dealing with the diagnosis and treatment of attention deficit disorder (ADD, or minimal brain dysfunction) in adults. Subjects who met provisional operational criteria for adult ADD were entered in a random-assignment, parallel, double-blind trial of placebo and pemoline, a noneuphorigenic psychostimulant drug effective in children with ADD. There was improvement in both the pemoline group and the placebo group, but the difference in improvement was not statistically significant. When the analyses were confined to that subgroup of patients whose parents had described them in the 95th percentile of childhood "hyperactivity" or when the hyperactivity score was partialled out statistically, pemoline was demonstrably more effective than placebo. Revised operational criteria for adult ADD are proposed.

Diagnosis and treatment of minimal brain dysfunction in adults: a preliminary report.

Minimal brain dysfunction (MBD) has long been considered a disorder limited to childhood. A number of longitudinal and adoption studies suggest that MBD may persist into adult life where its existence is concealed by the application of a variety of diagnostic labels. In order to test the hypothesis that MBD does persist into adulthood, 15 putative MBD adults were identified on the basis of current MBD-like complaints, self-description of MBD characteristics in childhood, and a parental rating (on a standardized form) of "hyperactivity" in childhood. Eleven of the 15 subjects were given a double-blind trial of methylphenidate hydrochloride, and all 15 were given an open trial of pemoline, imipramine hydrochloride, or amitryptiline hydrochloride. Eight of the 11 showed a significant response to the double-blind trial of methylphenidate. Of the 15, eight showed a good response to stimulants or tricyclic antidepressants, two showed a moderately favorable response, and five were unresponsive to drug therapy.

The value of serum magnesium determination in hypertensive patients receiving diuretics.

Some clinicians contend that hypomagnesemia is a common problem in patients receiving diuretic therapy and that routine serum magnesium determinations may be indicated in such patients. We determined serum magnesium (Mg++) levels in 354 patients with uncomplicated hypertension. No significant difference was observed in the mean Mg++ between the 245 diuretic-treated patients and the 109 patients not receiving diuretics, 0.965 vs 0.97 mmol/L (1.93 vs 1.94 mEq/L). When analyzed by type of diuretic, there were statistically significant differences in the mean serum Mg++ concentrations between those receiving thiazides, 0.94 mmol/L (1.87 mEq/L); those receiving no diuretics, 0.97 mmol/L (1.94 mEq/L); and those receiving triamterene-containing diuretics, 1.01 mmol/L (2.01 mEq/L). These absolute differences, however, were clinically quite small, and hypomagnesemia was uncommon. Neither patient age, the duration of diuretic use, nor the serum potassium level correlated with Mg++. With respect to dose, those receiving 100 mg/d of hydrochlorothiazide had the lowest Mg++ concentrations and the greatest prevalence of hypomagnesemia (12%), defined as Mg++ less than 0.75 mmol/L (1.5 mEq/L). Serum Mg++ need not routinely be determined in patients with uncomplicated hypertension who are receiving triamterene-containing diuretics or low-dose (50 mg/d or less) hydrochlorothiazide.

An open trial of L-tyrosine in the treatment of attention deficit disorder, residual type.

To elucidate the role of catecholamines in attention deficit disorder, the authors conducted an open 8-week trial of L-tyrosine in 12 adults with attention deficit disorder, residual type. Eight showed marked to moderate clinical response in 2 weeks; at 6 weeks these eight developed tolerance, suggesting that L-tyrosine is not useful in attention deficit disorder, residual type.

An open clinical trial of L-dopa and carbidopa in adults with minimal brain dysfunction.

MBD has long been considered a childhood disorders. Recent research suggests that in some it persists into adult life and that at least one form is a consequence of reduced activity of dopaminergic systems in the brain. To test this hypothesis, three adults with "presumptive" MBD were given L-dopa plus carbidopa. Although overall this combination was less effective than stimulant medication, all the patients showed an initial response, and in one patient L-dopa seemed to potentiate the effect of methylphenidate. The authors point out that various dopamine agonists have different effects and that the possible potentiation effect is consistent with a dopaminergic hypothesis.

Changes in the time course of transmitter action produced by procaine.

1. In addition to reducing the sensitivity of the end-plate to transmitter, procaine produced changes in the time course of the end-plate potential. The time to peak potential was reduced by procaine, whether recording from fibres paralysed by tubocurarine or from fibres paralysed by high magnesium concentration. The rate of decay of potential was also markedly reduced. Similar observations were made recording spontaneous miniature end-plate potentials.2. Procaine did not produce any marked change in the electrical constants of muscle fibres.3. In the presence of procaine the accumulation of charge at the end-plate was prolonged; the rate of decay of charge was reduced. It is suggested that the prolonged end-plate potentials arise from a prolongation of the end-plate current.

On the neuromuscular paralysis produced by procaine.

1. The effects of procaine on neuromuscular transmission in the rat phrenic nerve diaphragm preparation have been examined using intracellular recording techniques.2. The paralysis produced by procaine resembled that produced by tubocurarine and it is concluded that this effect of procaine results from a change in post-junctional sensitivity to transmitter; at low rates of stimulation procaine did not depress the transmitter release.3. During high frequency stimulation of the phrenic nerve a distinct form of prejunctional failure was observed. It is suggested that this depression results from a combination of local anaesthesia and anoxia and that it would explain reports of a reduction in the amount of transmitter released when assayed in a conventional manner.

Arbaprostil's [15(R)-15-methyl PGE2] effects on intrauterine pressure in the nonpregnant and pregnant human female--a report of four clinical trials.

Four clinical trials evaluating arbaprostil's effects on the human uterus are reported. The initial two trials measured intrauterine pressures in nonpregnant and pregnant human females following arbaprostil doses of 10, 25, and/or 50 mcg. No statistical differences were found at any dosage level in either study for average uterine resting pressures, average peak pressures, the number of contractions or Montevideo units. Subsequently, two trials determined the abortifacient potential of arbaprostil in pregnant women during the first trimester. The first utilized total daily doses of 400 and 800 mcgs. while the second used total daily doses of 1200 and 1600 mcgs. Vaginal spotting was noted in one woman receiving 400 mcgs, three receiving 1200 mcgs. and in two receiving 1600 mcgs. One episode of moderate bleeding was seen in the latter study. Based on these studies, arbaprostil exhibits little potential for inducing abortifacient activity at these dosages in these patient populations.

Effectiveness of ranitidine 150 mg at bedtime as maintenance therapy for healed gastric ulcers.

As many as 89% of gastric ulcer patients experience ulcer recurrences within 1 year of successful healing with conventional antiulcer therapies. Because ranitidine is effective in the healing of gastric and duodenal ulcers and the maintenance of healed duodenal ulcers, we hypothesized that ranitidine would also be effective in the maintenance of healed gastric ulcers. A 48-week, placebo-controlled, randomized, double-blind, multicenter trial was conducted to compare ranitidine 150 mg administered at bedtime with placebo for the maintenance of healed gastric ulcers. Endoscopies were performed at baseline and repeated after 12, 24, 36, and 48 weeks of treatment. Gastric ulcer recurrence rates at each scheduled endoscopy were significantly lower in patients receiving ranitidine (5%, 13%, 16%, and 19%, respectively) compared with those receiving placebo (20%, 30%, 40%, and 50%, respectively). Compared with placebo, ranitidine was more effective in maintaining healed gastric ulcers regardless of previous gastric ulcer history, smoking status, age (< 65 vs > or = 65 years), or sex. There were no significant differences between the two treatment groups in the number of patients experiencing adverse events or laboratory abnormalities. Ranitidine 150 mg administered at bedtime provides safe and effective treatment for the maintenance of healed gastric ulcers.

Treatment of attention deficit disorder with DL-phenylalanine.

Nineteen patients meeting the criteria for attention deficit disorder, residual type (adult hyperactivity), were given a 2-week double-blind crossover of DL-phenylalanine versus placebo. Thirteen subjects completed the study; the mean global rating of improvement approached significance as compared with placebo. A significant improvement was noted on mood and mood lability. The phenylalanine responders were then continued on open drug, but lost all positive benefits within 3 months. A later open trial of L-phenylalanine produced no clinical effect.

An open trial of pargyline in the treatment of attention deficit disorder, residual type.

Twenty-two patients who met the Utah criteria for attention deficit disorder, residual type (hyperactivity, minimal brain dysfunction in adults) received an open trial of pargyline (Eutonyl). Of these 22 patients, 13 (59%) showed a moderate to marked therapeutic response. Clinically useful features of pargyline in the treatment of attention deficit disorder, residual type are that its duration of action is greater than 24 hours and that it has not been abused. Pargyline inhibits monoamine oxidase, type B, and its therapeutic efficacy is compatible with the hypothesis that decreased phenethylaminergic function, dopaminergic function, or both play a role in the etiology of the disorder.

Cerebrospinal fluid homovanillic acid and 5-hydroxy-indoleacetic acid in adults with attention deficit disorder, residual type.

Following the hypothesis that attention deficit disorder in adults (attention deficit disorder, residual type; ADD, RT), as well as in children, is associated with decreased central dopaminergic activity, the authors measured lumbar cerebrospinal fluid monoamine metabolites in a group of adults with ADD, RT and matched control subjects. Patients were then entered into a double-blind, placebo-controlled trial of methylphenidate. It was predicted that the patients would have lower levels of homovanillic acid (HVA), the major dopamine metabolite in humans. Patients who had a significant response to methylphenidate showed a trend in this direction. Nonresponding patients had significantly higher levels of HVA than controls.

Development of a scoring system to predict mortality from upper gastrointestinal bleeding.

Despite the widespread application of endoscopy in acute upper gastrointestinal bleeding, there is little evidence of improved survival among those who undergo the procedure. To select high-risk patients who might benefit most from diagnostic and therapeutic endoscopy, the authors developed and validated a scoring system based on prognostic indicators of increased mortality. The scoring system was developed from the best clinical predictors of mortality, determined in a prospective study of consecutive bleeding patients. The model was then tested in a prospective validation phase at three hospitals. Three main factors in the model predict mortality: bleeding, including hematochezia, drop in hematocrit of 5%, short duration of bleeding, absence of melena, and hypotension; liver disease, manifested by prolonged prothrombin time and encephalopathy; and renal disease. Patients determined to be at high risk for death using the scoring system might be candidates for aggressive management and for therapeutic endoscopy.

Improved high-intensity microwave discharge lamp for atomic resonance absorption and fluorescence spectrometry.

An unusually good combination of high intensity and narrow line has been achieved in a microwave discharge lamp by placing the optical window in the center of the microwave cavity. Construction details and performance characteristics are described.

Effect of an upper-arm constricting device on arm blood pressure measurements.

Thousands of blood pressure measurements are done daily without the patients' disrobing. This study was therefore undertaken to determine the validity of such measurements, especially those taken when the patient's armsleeve has been rolled up onto the proximal aspect of the arm. An inflatable constricting device was applied to the proximal aspect of the arm and a standard sphygmomanometer was applied distal to the inflatable cuff. The constricting cuff was inflated to 0, 20, 40, 60, 80, and 100 mm Hg in random sequence, and the blood pressure was recorded at each level. Statistically significant elevations in the mean systolic blood pressure were detected at proximal constricting pressures of 80 mm Hg (P less than .01) and 100 mm Hg (P less than .001), and in the mean diastolic blood pressure at 20 mm Hg (P less than .005). However, the magnitude of the elevations was small: 3.9, 4.4, and 2.5 mm Hg, respectively. We conclude that though a proximal constricting device may induce statistically significant alterations in blood pressure measurements these alterations are small and not likely to affect treatment decisions.