Plasma nitrogen oxides and blood lactate concentrations in Ghanaian children with malaria

OBJECTIVES: To titrate a clinically effective eltenac dosage (0.1, 0.5, and 1.0 mg/kg of body weight), compared with vehicle only, and to compare efficacy of the most effective eltenac dosage with that of 1.1 mg of flunixin meglumine/kg. ANIMALS: 40 healthy horses, ranked after model induction on the basis of lameness severity, were randomly assigned to 5 treatment groups, with 4 replicates of 10 horses each. PROCEDURE: On day -5, after surgical preparation of the left carpal region, 0.7 ml of Freund's complete adjuvant was injected into the intercarpal space. Horses were observed daily, from the day of carpitis induction to day 0, when stride length was used as the method of ranking horses for randomization to treatment assignment. Treatments were administered i.v. once daily for 3 consecutive days, starting on day 0. Prior to carpitis induction on day -5, and at time 0 (pretreatment), 2, 4, 12, 24, 36, 48, 60, 72, and 96 hours after treatment initiation, resting respiratory rate and pulse, rectal temperature, carpal circumference, carpal flexion angle, stride length, carpal hyperthermia, and signs of carpal pain were recorded. RESULTS: Compared with the vehicle and 0.1 mg of eltenac/kg, 0.5 and 1.0 mg/kg caused statistically significant improvements (ie, reduction of carpal circumference, increase in carpal flexion angle, and increase in stride length of the affected limb), but values did not differ significantly between the 2 dosages. Thus, a dose-response plateau for eltenac was reached at 0.5 mg/kg. Comparison with flunixin meglumine at a dosage of 1.1 mg/kg did not indicate significant differences between the 2 treatment groups at the pivotal time of 96 hours for carpal circumference, carpal flexion angle, stride length, carpal hyperthermia, and signs of carpal pain. Adverse reactions were not observed. CLINICAL RELEVANCE: Under conditions of this study, a dosage plateau for eltenac was determined (0.5 mg/kg) that was statistically equivalent to eltenac (1.0 mg/kg) and flunixin meglumine (1.1 mg/kg) in a 3-day i.v. dosing regimen.     

Field study of undifferentiated respiratory disease in housed beef calves

A severe outbreak of undifferentiated respiratory disease affecting 119 of 144 (82.6 per cent) two- to five-month-old housed beef calves was studied by monitoring their clinical signs and rectal temperatures daily or every second day for two months. New cases of respiratory disease, which were first identified three weeks after the calves were housed, occurred over a period of 29 days. The cause of the outbreak was not conclusively determined although 20 per cent of the calves sampled showed serological evidence of recent infection with bovine respiratory syncytial virus and parainfluenzavirus 3. Seventeen of 61 calves (27.9 per cent) which were treated with tilmicosin had to be treated again, compared with nine of 58 calves (15.5 per cent) which were treated with both tilmicosin and flunixin meglumine and did not need further treatment, but this difference was not statistically significant.     

Effect of phenylbutazone and flunixin meglumine on acute toxic mastitis in dairy cows

A double-blinded randomized prospective clinical trial was designed to evaluate the effectiveness of flunixin meglumine and phenylbutazone for treatment of acute toxic mastitis in dairy cows. All cows were treated 4 times at 12-hour intervals by intramammary infusion of gentamicin (150 mg). A total of 45 dairy cows with toxic mastitis were randomly assigned to 1 of 3 treatment groups: group 1 (control), saline solution, IV; group 2, 1 g of flunixin meglumine, IV; or group 3, 4 g of phenylbutazone, IV. Physical examination and udder variables were assessed at initial examination and 24 hours later. Milk production was recorded at regular intervals from 1 week before until 10 weeks after development of mastitis. Rear quarters (34/45) were more commonly affected than front quarters. Thirty-five cows returned to the herd, 9 cows were culled, and 1 cow died. There were no significant differences among treatment groups in the need for further treatment or outcome. Klebsiella spp (18/45) and Escherichia coli (16/45) were the most common pathogens isolated by culture of milk from affected quarters. The overall bacteriologic cure rate on days 7 and 14 was 64 and 75%, respectively. At the time of initial examination, cows of the control group had higher rectal temperature than did cows of the flunixin group. At the examination 24 hours later, the rectal temperature of cows in all treatment groups was lower than the temperature at initial examination; at that time (24 hours), however, there were no significant differences in temperature among the treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measurement of cyclooxygenase inhibition in vivo: a study of two non-steroidal anti-inflammatory drugs in sheep

The anti-inflammatory effects of the non-steroidal anti-inflammatory drugs phenylbutazone (PBZ) and flunixin meglumine (FM) and the relationship between the effects and drug concentration in vivo were studied using a subcutaneous tissue-cage model in sheep. Intracaveal injection of carrageenan induced prostaglandin (PG) E2 production in tissue-cage exudate (maximal concentration, 101 nM) with significant increases in white blood cell (WBC) numbers, skin temperature over the inflamed cage and exudate leukotriene B4 (LTB4) concentration (P < 0.05). Intravenous PBZ, 4.4 mg kg-1 produced mild inhibition of exudate PGE2 generation (10%), but greater inhibition of serum TXB2 (75.3%). The IC50 for TXB2 was 36.0 microM. Phenylbutazone did not alter effects on skin temperature, WBC numbers or exudate LTB4 concentrations. Intravenous FM, 1.1 mg kg-1, significantly inhibited carrageenan-induced exudate PGE2 formation (Emax, 100%, IC50, < 0.4 nM) and serum TXB2 generation (Emax, 100%, IC50, 17 nM) for up to 32 h. Flunixin meglumine significantly inhibited the rise in skin temperature but had a limited effect on exudate WBC. Phenylbutazone and FM have distinct effects on carrageenan-induced cyclooxygenase (COX-2) and platelet COX (COX-1). Flunixin meglumine was a more potent COX inhibitor than PBZ and was more selective for the inducible form of COX in vivo.     

Effect of flunixin meglumine on plasma prostanoid concentrations in horses with colic in the perioperative period

In the present study the significance of eicosanoids in the development of shock in horses on the basis of ileus has been investigated using the prostanoids thromboxane B2 (TXB2) and prostaglandine E2 (PGE2) as indicators. The prostanoid synthesis inhibitor flunixin meglumine was to be examined regarding its efficacy in the effective blockade of the synthesis of these mediators within the peri-operative timeframe as well as its effects on clinical signs and laboratory parameters. 21 horses suffering from ileus and ready for surgical intervention received an intravenous flunixin dosis of 1.1 mg/kg body weight immediately after the initial examination and prior to the surgical procedure. 20 colic horses receiving surgical treatment without application of the drug served as control group. Reference data concerning the approximate standard plasma levels of the prostanoids were determined in 10 healthy horses. Plasma levels of thromboxane B2 and prostaglandine E2 in all colic horses, treatment group as well as controls, initially proved to be significantly higher than the reference values in healthy horses. The untreated control group showed plasma levels highly exceeding the standards within the course of investigation. The application of flunixin meglumine resulted in an effective inhibition of the prostanoid synthesis. Post-operatively as well as within the whole period of investigation the plasma levels of PGE2 and TXB2 of the treated group were considerably lower than those of the control group. Flunixin meglumine had a favorable effect on several cardiovascular parameters. The experimental data concerning the effects of flunixin meglumine thus could be validated in a clinical setting, especially the effective inhibition of the cyclooxygenase enzyme system. The application of the prostanoid synthesis inhibitor flunixin meglumine can be judged as being effective in limiting shock progress in the peri-operative setting given reliable diagnosis.     

Comparison of fluid and flunixin meglumine therapy in combination and individually in the treatment of toxic mastitis

During a three-year study, 54 cows with toxic mastitis were allocated randomly to one of three treatment groups (A, B and C). Each cow was re-examined within 24 hours of the initial examination, and, during this time, group A received fluid therapy (45 liters of intravenous isotonic electrolyte solution) and flunixin meglumine (2000 mg), group B received fluid therapy only, and group C received flunixin meglumine only. In addition all the cases were treated with parenteral and intramammary tetracyclines, oxytocin and calcium boroglucoanate. There was no significant difference in the rate of survival between the treatment groups and 29 of the cows (53.7 per cent, 95 per cent confidence interval of 39 to 67 per cent) survived.     

Rhythmic activities of hypothalamic magnocellular neurons: autocontrol mechanisms

A study was conducted in western Canada to evaluate the efficacy of florfenicol for the treatment of undifferentiated fever (UF) in feedlot calves. One hundred and twenty-five recently weaned, auction market derived, crossbred, beef steer calves suffering from UF were allocated to 1 of 2 experimental groups as follows: florfenicol, which was intramuscular florfenicol administered at the rate of 20 mg/kg body weight at the time of allocation (day 0) and again 48 h later; or control, which was intramuscular saline administered at the same volume as florfenicol at the time of allocation and again 48 h later. Eighty-four calves were allocated to the florfenicol group and 41 calves were allocated to the control group. Outcome measures describing animal health, body weight, and rectal temperature parameters were used to determine the efficacy of florfenicol for the treatment of UF. The 1st relapse of UF, 2nd relapse of UF, overall mortality, bovine respiratory disease mortality, and haemophilosis mortality rates were significantly (P < 0.05) lower in the florfenicol group than in the control group. Animals in the florfenicol group were significantly (P < 0.05) heavier at day 15 and day 45 than animals in the control group. The rectal temperature on days 1, 2, 3, and 4 of animals in the florfenicol group was significantly (P < 0.05) lower than in the control group. In addition, the change in rectal temperature from day 0 to day 4 was significantly (P < 0.05) different between the experimental groups. The results of this study demonstrate that florfenicol is an efficacious antimicrobial for the treatment of UF.     

The tuberculin skin test in BCG-vaccinated individualse]

Endoscopy was undertaken to examine the gastroduodenal mucosa of 24 healthy dogs after seven days and again after 28 days of oral non-steroidal anti-inflammatory drug (NSAID) administration. The dogs were divided into four groups. One group received ketoprofen (1 mg/kg every 24 hours), one group carprofen (2 mg/kg every 12 hours for seven days followed by 2 mg/kg every 24 hours), a third group meloxicam suspension (0.2 mg/kg every 24 hours), and the last group gelatin (one capsule every 24 hours). Serum biochemical and complete blood count parameters did not change significantly after NSAID administration. Gastroduodenal lesions were observed in 17 dogs, but in all cases these were mild to moderate. The dogs receiving gelatin or carprofen showed the fewest and the least severe lesions, although there was no statistically significant difference between the three test drugs and the control group (P < or = 0.05). None of the dogs showed any clinical signs related to the gastrointestinal lesions.     

Glucose transport in the small intestine of rats following section of the pancreatico-biliary duct]

Decoquinate administered orally in a grain mix at dosages of 0.5, 0.538, 0.7, and 0.8 mg/kg of body weight suppressed oocyst discharge and bloody diarrhea in calves inoculated 3 days later with 100,000 oocysts of Eimeria bovis (experiment 1, n = 12 calves) or with 100,000 oocysts each of E bovis and Eimeria zuernii (experiment 2, n = 16 calves). Doses of 0.1, 0.163, 0.243, 0.3, and 0.362 mg/kg of body weight gave only partial suppression of oocyst discharge and diarrhea. Clinical signs of coccidiosis did not recur for 23 days after the treatment was discontinued.     

Study of factors affecting the determination of total plasma 7-fluorobenzo-2-oxa-1,3-diazole-4-sulfonate (SBD)-thiol derivatives by liquid chromatography

A flunixin metabolite, a hydroxylated product, has been identified in camel urine and plasma samples using gas chromatography-mass spectrometry (GC-MS) and GC-MS-MS in the electron impact and chemical ionization modes. Its major fragmentation pattern has been verified by GC-MS-MS in daughter ion and parent ion scan modes. The method could detect flunixin and its metabolite in camel urine after a single intravenous dose of 2.2 mg of flunixin/kg body weight for 96 and 48 h, respectively, which increases the reliability of antidoping control analysis.     

Effects of arrival medication with tilmicosin phosphate on health and performance of newly received beef cattle

Three trials were conducted to evaluate the use of tilmicosin phosphate (Micotil) as a prophylactic medication for newly received, stressed beef cattle. In Trial 1, 57 beef calves (average initial BW = 170 kg) were shipped to the research feedlot from Tennessee and either given no antibiotic at processing or treated with Micotil at 10 mg of tilmicosin phosphate/kg of BW. During a 28-d receiving period, treatment at processing with Micotil did not affect daily gain (P < .17) or DMI (P < .22) compared to control calves. Prophylactic treatment with Micotil decreased (P < .01) the percentage of calves treated for symptoms of bovine respiratory disease from 46.4 to 0%. In Trial 2, 117 calves (average initial BW = 191 kg) were shipped from Tennessee and allotted randomly to the same two treatments as in Trial 1. All calves grazed a 24-ha pasture of irrigated winter wheat during the 28-d receiving period. Treatment of calves with Micotil at the time of arrival processing did not affect (P > .50) daily gain during the trial; however, as in Trial 1, mass treatment with Micotil decreased (P < .01) the percentage of calves treated for respiratory disease from 32.8% to 12.1%. In Trial 3, two truckloads of beef calves (183 total; average initial BW = 232 kg) shipped from Tennessee were allotted randomly to the same two treatments used in Trials 1 and 2 or to a third treatment that consisted of administration of Micotil at arrival processing if the rectal temperature of the calf was > or = 39.7 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of infarct artery patency on prognosis after acute myocardial infarction. The Survival and Ventricular Enlargement Investigators

In this study, adult male rats were injected intraperitoneally with a single dose of serotonin (5-hydroxytryptamine, 5HT; 10 mg kg-1 bodyweight) for 2 h or 18 h, or daily with graded doses of 5HT (0.1-10 mg kg-1) for four days before being killed. Serum and testicular interstitial fluid (IF) concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and immunoreactive-inhibin were measured by radioimmunoassay, and one testis was removed for histological examination. At 2 h after a single injection, 5HT caused a significant inhibition of serum concentrations of LH and inhibin, recovered IF volume and intratesticular testosterone concentrations; testis weight and serum concentrations of testosterone and FSH were unaffected. At 18 h after injection, all parameters had returned to normal, with the exception of intratesticular testosterone concentration which remained lower than normal. The lowest 5HT dose (0.1 mg kg-1) had no effect on any parameter following four daily injections. At a dose of 1.0 mg kg-1 5HT, there was a four-fold increase in the concentration of serum LH, but testis weight, recovered IF volume, testosterone and inhibin concentrations and serum concentrations of FSH were not significantly affected. At the highest dose of 5HT (10 mg kg-1) after four daily injections, testis weight decreased, and IF volume increased nearly three-fold. Testis concentrations of inhibin and serum testosterone were reduced, whereas serum concentrations of both LH and FSH were elevated; intratesticular testosterone concentrations did not differ from controls. Only at the highest dose of 5HT was disruption to the seminiferous epithelium observed, with focal damage ranging in severity from increased degeneration of spermatogenic cell profiles, to complete loss of the germinal epithelium; however, many tubule profiles displayed completely normal spermatogenesis. The acute IF volume reduction and spermatogenic disruption in 5HT-treated rats were consistent with localized ischaemia due to constriction of the testicular arterial supply. The eventual increase in IF volume observed after 5HT treatment appeared to be secondary to the loss of germ cells. Although 5HT also inhibited pituitary LH release and Leydig cell steroidogenesis, these effects appeared to play only a minor role in the induction of spermatogenic damage.     

Influence of dexamethasone on the recrudescence of Anaplasma marginale in splenectomized calves

Dexamethasone was administered at the dose rate of 0.2 mg/kg of body weight to 11 splenectomized Anaplasma-carrier calves (groups 1 and 3) on Monday, Wednesday, and Friday for 3 weeks. Observations were made on these calves and on 7 nontreated, comparable calves (group 2) to determine the influence of treatment on carrier infections. Dexamethasone treatment was associated in every instance with an exacerbation of the Anaplasma parasitemia and a decrease in packed red cell volume. The episode of acute anaplasmosis was of short duration, resembling the primary response, except that complement-fixation response did not increase accordingly. Serum protein electrophoresis of serums from 4 calves (group 3) undergoing the drug-induced response failed to show any significant change during the 3-week treatment period, but did show a significant increase in gamma-globulin immediately after treatment.     

Systemic injections of ciliary neurotrophic factor induce sprouting by adult motor neurons

The ability of ciliary neurotrophic factor (CNTF) to induce sprouting by undamaged adult motor neurons was studied in gluteal muscles of adult ICR mice. Low doses of CNTF (0.02 mg kg-1 day-1) only induced sprouting in gluteus muscles that were beneath the site of injection, whereas high doses of CNTF (0.4-1.2 mg kg-1 day-1) acted systemically to induce motor neuron sprouting. We found little difference between the type or quality of sprouting induced by CNTF compared with muscle paralysis. Both stimuli induced sprouts of the same length, although muscle paralysis tended to induce more sprouts per end-plate. Paralysis also induced more nodal sprouting than did CNTF, but both were weaker stimuli for nodal sprouting than was partial denervation. In addition to its effects on motor neuron sprouting, high doses of CNTF induced loss of up to 36% of the body weight of treated mice. The substantial wasting caused by CNTF indicates that the factor has potent cachectic activity.     

The role of employers in community health care systems

The postoperative analgesia and sedation in cats given carprofen (4.0 mg/kg bodyweight by subcutaneous injection preoperatively) was compared to that in cats given pethidine (3.3 mg/kg bodyweight by intramuscular injection postoperatively) in a controlled, randomised, blinded, multicentre clinical trial. Further dosing with the particular analgesic was allowed if a cat was exhibiting unacceptable pain. In total, 57 carprofen cases and 59 pethidine cases were evaluated. Significantly fewer cats in the carprofen group required additional doses of analgesic, and mean pain scores were significantly lower from four hours after ovariohysterectomy, and at 18 to 24 hours after castration, compared to the pethidine group. In conclusion, carprofen provided as good a level of postoperative analgesia as pethidine, but of a longer duration (at least 24 hours) and was well tolerated. It thus provides an option for 'pre-emptive analgesia' in cats about to undergo surgery.     

The breast cancer screening controversy and the National Institutes of Health Consensus Development Conference on Breast Cancer Screening for Women Ages 40-49

PURPOSE: Unaccustomed exercise is associated with an elevated plasma creatine kinase (CK), myofibrillar inflammation, and delayed onset muscle soreness (DOMS). Nonsteroidal antiinflammatory drugs (NSAID) may attenuate DOMS and indirect indices of inflammation in humans. METHODS: We studied the effects of an NSAID (naproxen sodium (500 mg, 2 times a day for 48 h)) taken before and after resistance exercise in eight healthy, moderately trained men in a randomized, double-blind trial. The exercise consisted of unilateral knee concentric/eccentric weight lifting with 6 sets x 10 repetitions at 80-85% of the 1 repetition maximal contraction. Muscle biopsies of each vastus lateralis (EX = exercised/REST = control) were taken 24 h after exercise for immunohistochemical staining of inflammatory cells (leukocyte common antigen). At 24 and 48 h postexercise, we also determined DOMS, plasma CK activity, and knee extensor muscle torque. RESULTS: Exercise resulted in an increased CK activity at +24 and +48 h (vs preexercise: P < 0.01), with no treatment effect. There were no treatment effects for any of the measured variables except for a return of voluntary knee extension torque to baseline by +48 h postexercise for NSAID treatment (P < 0.05). CONCLUSIONS: NSAID administration did not alter CK rise, muscle force deficit at 24 h postexercise, nor perceived muscle pain. In addition, the increased CK at 24 h postexercise was not associated with an acute myofibrillar inflammatory cell infiltrate in moderately trained men after resistance exercise.     

Randomized trial of the addition of gram-positive prophylaxis to standard antimicrobial prophylaxis for patients undergoing autologous bone marrow transplantation

The purpose of the study reported here was to investigate the impact of prophylaxis against gram-positive infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplantation in a randomized trial. Forty-three patients undergoing high-dose chemotherapy with autologous bone marrow transplant were enrolled in a nonblinded randomized trial to receive or not to receive prophylaxis for gram-positive infections with 10(6) U of penicillin intravenously (i.v.) every 6 h (q6h) (if penicillin allergic, 750 mg of vancomycin i.v. q12h) in addition to standard antimicrobial prophylaxis with 400 mg of norfloxacin orally three times a day, 200 mg of fluconazole orally once a day, and 5 mg of acyclovir per kg of body weight i.v. q12h. The patients were being treated for germ cell cancer (n = 15), breast cancer (n = 16), Hodgkin's disease (n = 3), non-Hodgkin's lymphoma (n = 4), acute myeloid leukemia (n = 1), acute lymphoblastic leukemia (n = 1), and ovarian cancer (n = 3). The trial was stopped because of excess morbidity in the form of streptococcal septic shock in the group not receiving gram-positive prophylaxis. There were significantly fewer overall infections (10 versus 3; P = 0.016) and streptococcal infections (9 versus 1; P = 0.0078) in the group receiving gram-positive prophylaxis. There were no significant differences in the numbers of deaths, duration of broad-spectrum antibiotics, or incidence of neutropenic fever between the two groups. Prophylaxis for gram-positive infections with penicillin or vancomycin is effective in reducing the incidence of streptococcal infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplant. However, this approach may carry a risk of fostering resistance among streptococci to penicillin or vancomycin.     

Prophylactic efficacy of tilmicosin for bovine respiratory tract disease

The prophylactic administration of injectable tilmicosin for pneumonia in weaned beef calves was investigated in 1,806 animals. Comparisons were made among calves receiving an "on-arrival" injection of tilmicosin, calves receiving a single injection of long-acting oxytetracycline, and calves receiving no prophylaxis. Morbidity and mortality attributable to pneumonia, morbidity and mortality attributable to all causes, and case fatality were significantly lower in the group of calves that received tilmicosin, compared with calves that received long-acting oxytetracycline and calves that received no prophylactic antibiotic. Mean time to initial pneumonia treatment was significantly extended in calves that received prophylaxis, compared with those that received no antibiotic on arrival at the feedlot. Calves that received tilmicosin gained significantly more weight than calves that received oxytetracycline. Calves that were not treated for pneumonia during the trial period gained significantly more weight than did those calves that were treated for pneumonia regardless of experimental group. The majority of mortalities were attributable to fibrinous pneumonia (31/34). Important bacterial isolates (Pasteurella spp, Haemophilus somnus, Actinomyces pyogenes) obtained at necropsy did not have resistance to tilmicosin in association with administration of tilmicosin as prophylaxis for pneumonia. However, bacterial resistance to trimethoprim/sulfonamide and to oxytetracycline were commonly found in these postmortem isolates.     

Role of the steady-state Na+ channel current in pacemaker depolarizations in young embryonic chick ventricular myocytes

Thresholds to noxious mechanical and thermal stimulation were measured in 6 groups of sheep prior to induction of anaesthesia and subsequently for a period of 2 h in the post-anaesthetic period. Groups 1-4 were anaesthetised using thiopentone and underwent ventral midline laparotomy. Four animals (group 5) underwent anaesthesia but not surgery, and a further 6 sheep (group 6) undergoing surgery were anaesthetised using ketamine. Groups 1-3 were intravenously administered the following drugs intra-operatively: flunixin meglumine, carprofen and buprenorphine, respectively. Groups 4-6 received no additional treatment. Thresholds to the mechanical test were not changed in the post-anaesthetic period for any group. There was a significant reduction in the responses to thermal stimulation after surgery for sheep in group 4 (45 and 60 min), while sheep in group 2 had thresholds to thermal stimulation greater than those recorded in the remaining groups at all time points post-operatively. Responses to thermal stimulation in sheep undergoing anaesthesia but not surgery (group 5) were unaltered during the 2 h recording period after anaesthesia ended. These data indicate that abdominal surgery induces thermal but not mechanical hyperalgesia in sheep, which appears to be centrally mediated. Moreover, the absence of mechanical hyperalgesia raises the possibility that central changes in noxious information processing may not be detected using mechanical stimuli in the same time course as thermal stimuli.