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PubMed1998

Induced and synchronized estrus in cattle: dose titration of estradiol benzoate in peripubertal heifers and postpartum cows after treatment with an intravaginal progesterone-releasing insert and prostaglandin F2alpha.

Peripubertal beef heifers (n = 57) and postpartum multiparous cows (n = 52) were used to determine the optimal dose of estradiol benzoate (EB) to induce and synchronize estrus after treatment with intravaginal progesterone inserts (IVP4, EAZI-BREED CIDR). All females received an IVP4 for 7 d (d 0 = insertion day) with a 25-mg injection of PGF2alpha (Lutalyse) on d 6. At 24 to 30 h after IVP4 removal, females were randomly assigned to be injected subcutaneously with EB at the following doses: heifers 0, .2, .38, or .75 mg and cows 0, .25, .5, or 1 mg. Furthermore, seven heifers and seven cows from each dose group were bled every 4 h for 76 h starting at EB injection. Serum was collected and assayed for LH and estradiol-17beta (E2). Observations for signs of estrus were made twice daily for 21 d after removal of IVP4, and females were artificially inseminated 8 to 20 h after detection of estrus. The percentage of females showing estrous behavior was increased by EB (P < .04); the greatest response was at .38 mg in heifers (86%) and 1 mg in cows (100%). Dose x time interaction affected (P < .01) E2 concentrations in heifers and cows; the animals that received the higher doses of EB had greater E2 concentrations in a shorter time than those that received the smaller doses. The percentage of cows and heifers with an acute preovulatory LH release (peak LH) was affected by dose, with a linear (P < .01) and a quadratic (P < .01) response. Highest concentrations of LH during peak LH were affected by dose with a linear (P < .01) response in heifers and linear (P < .01) and quadratic (P < .08) responses in cows. Heifers receiving .38 mg and cows receiving .5 and 1 mg of EB had the highest peak LH. Time to LH peak had a linear (P < .03) response in heifers and had linear (P < .04) and quadratic (P < .05) responses in cows. Pregnancy rate was affected (P < .02) in heifers by whether or not they were anestrous before IVP4 treatment (those with estrous cycles = 52% vs those that were anestrous = 22%) and in cows by dose of EB (P < .01; 8, 23, 21, and 67% for 0, .25, .5, and 1 mg, respectively). In conclusion, in females treated with IVP4 and PGF2alpha to induce and synchronize estrus, an injection of EB increased concentrations of E2 and LH and increased number of animals showing estrus. Also, EB increased pregnancy rates in cows. Optimal responses were at .38 mg EB for heifers and at 1 mg EB for cows.

Administration, Intravaginal↗
PubMedDate not supplied

Dose-titration of fenbendazole in the treatment of poultry nematodiasis.

Broiler chickens were fed ad libitum diets containing fenbendazole at various concentrations and durations for the removal of adult Ascaridia galli, Heterakis gallinarum, and Capillaria obsignata. All regimens were 100% effective against A. galli. Fenbendazole at doses of 80 ppm for 3 days and 48 or 30 ppm for 5 days was 100% effective against H. gallinarum. C. obsignata was not removed completely by any regimen, but greater than or equal to 95% effectiveness was seen in birds given fenbendazole at doses of 80 ppm for 3 days and 48 ppm for 5 days. All medicated rations were readily consumed, and the treated birds exhibited no adverse reactions.

Administration, Oral↗
PubMedDate not supplied

Dose titration study of enrofloxacin (Baytril) against respiratory colibacillosis in Muscovy ducks.

Four-week-old specific-pathogen-free Muscovy ducks were inoculated with reovirus. One week later, they were inoculated intratracheally with a O78:K80 strain of Escherichia coli. The next day, they were given enrofloxacin at different doses in the drinking water. Comparison of mortality rates, weight gain, macroscopic lesions, and E. coli re-isolations among treated and untreated birds showed that a 5-day treatment course with 12.5 or 25 ppm enrofloxacin in water for 4 hours in the morning provided good therapeutic efficacy against respiratory colibacillosis.

Animals↗
PubMed2000

Docetaxel-induced mobilization of hematopoietic stem cells in a murine model: kinetics, dose titration, and toxicity.

OBJECTIVE: Docetaxel (DXT) is an anticancer agent that has demonstrated therapeutic efficacy against solid tumors, particularly breast cancer. Based on the use of hematopoietic stem cell (HSC) transplantation to restore hematopoietic reconstitution after myeloablative therapy, this study was performed to determine if DXT could mobilize HSCs in vivo. MATERIALS AND METHODS: C57Bl/6 mice were injected intraperitoneally with varying doses of DXT (equivalent to human doses of 40 to 120 mg/m(2)). Spleens were harvested on days 2, 4, 6, 8, 10, and 12 after DXT administration for recovery of mononuclear cells (MNCs). The number of HSCs present within the MNCs was determined by clonogenic assay for colony-forming units in culture (CFU-C) and by FACS analysis for CD34(+) cells. Peripheral blood samples were obtained at the time of spleen harvest to determine the hematologic profile. Liver and renal function tests were performed to monitor toxicity. RESULTS: DXT mobilize d HSCs in a dose- and time-dependent manner. When measured by the CFU-C assay, maximal mobilization of HSC (>10-fold increase in control; p<0.01) was observed at a dose of 30 mg/kg (equivalent to human dose of 75 mg/m(2)) on day 7. The number of mobilized HSCs peaked on days 6 to 8 at all doses of DXT tested. There was no evidence of weight loss, liver, or renal toxicity at any of the DXT doses tested. CONCLUSION: These results indicate that DXT efficiently mobilizes HSCs in a murine model and provide the rationale for similar studies in a clinical trial.

Animals↗
PubMed1998

Phase II trial with dose titration of paclitaxel for the therapy of human immunodeficiency virus-associated Kaposi's sarcoma.

PURPOSE: To investigate the antitumor activity and safety of paclitaxel in patients with advanced human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS). PATIENTS AND METHODS: Twenty-nine patients with advanced HIV-associated KS were enrolled. The patients were overall quite immunosuppressed (median CD4 count, 15 cells/microL). Paclitaxel was initially administered at 135 mg/m2 over 3 hours every 3 weeks without filgrastim support; the dose was increased as tolerated to a maximum of 175 mg/m2. Patients who failed to respond or progressed could then receive filgrastim support or paclitaxel administered over 96 hours. RESULTS: Of 28 assessable patients, 20 had major responses (18 partial responses [PRs], one clinical complete response [CR], and one CR), for a major response rate of 71.4% (95% confidence interval [CI], 51.3% to 86.8%). Each of the five patients with pulmonary KS responded, as did all four assessable patients who had previously received anthracycline therapy for KS. Of six patients who went on to receive a 96-hour infusion of paclitaxel, five had major responses. Neutropenia was the most frequent dose-limiting toxicity; possible novel toxicities included late fevers, late rash, and eosinophilia. Two patients developed an elevated creatinine concentration and one cardiomyopathy. CONCLUSION: Paclitaxel has substantial activity against advanced HIV-associated KS as a single agent, even in patients with pulmonary involvement or who had previously received anthracyclines. Further research is needed to define the optimal treatment schedule and its role vis-a-vis the other available therapies for this disease.

Acquired Immunodeficiency Syndrome↗
PubMed1982

Gene-dose titration analysis in the search of trans-regulatory genes in Drosophila.

We have searched for trans-regulatory genes in two genetic systems in Drosophila, the bithorax complex (BX-C) and the achaete-scute complex (AS-C). Previous genetic evidence suggests that the activation of both BX-C and AS-C, depends on trans-regulatory genes (Polycomb, Pc, in the former and hairy, h, in the latter) acting in a negative type of control. Mutants of these regulatory genes in heterozygous condition have dominant derepression phenotypes in flies with extra doses of the corresponding gene complexes. We have searched for new loci, with similar gene-dose relationships. We have isolated only new alleles (six) of Pc in the BX-C experiment. In the AS-C experiment four h alleles, and 13 alleles of a new locus (extramacrochaetae, emc) have been discovered. Whereas the h locus shows specific interactions upon achaete, the new locus, emc, is specific for the scute part of the AS-C. Statistical analysis suggests that these are the only loci in the genome with those dose-dependent properties in the two systems.

Alleles↗
PubMed2006

Dose titration of recombinant factor VIIa using thromboelastograph monitoring in a child with hemophilia and high titer inhibitors to factor VIII: a case report and brief review.

The administration of recombinant factor VIIa (rFVIIa) is complicated by a wide inter-subject variation in response, a short half-life, evolving indications for use, and the absence of a test that has been shown to correlate with clinical effect. This report describes a method used to titrate rFVIIa to thromboelastography (TEG) parameters in a difficult to manage hemophilic patient with high titer inhibition to factor VIII. The current concepts of monitoring rFVIla administration in hemophiliacs and uncontrolled hemorrhage in cardiac surgery are briefly reviewed.

Child↗
PubMed1995

Dose titration of moxidectin oral gel against gastrointestinal parasites of ponies.

Moxidectin was tested as an oral gel formulation during a controlled test performed to evaluate dosages against equine gastrointestinal parasites. Four groups of ten ponies were used. Ponies ranged from 1 to 20 years of age and were naturally infected in southern Louisiana or Mississippi. Fecal exams and fecal cultures were performed on all ponies to determine the strongyle egg counts and the percent distributions of large and small strongyles. Following these determinations, ponies were allocated to replicates of four ponies to provide an even distribution of strongyle infection, age, weight and gender. Members of each replicate were then randomly assigned to one of four treatment groups. The doses tested were 300, 400 and 500 micrograms kg-1 body weight. The oral gel vehicle alone served as control. Treatments were administered behind the tongue and the ponies were observed continuously for 4 h for any adverse reactions; thereafter, ponies were observed at least twice daily. Necropsy examinations were performed 14 days post-treatment for the recovery and identification of any parasites present. Moxidectin, at all doses tested, was 100% efficacious against adults of Strongylus vulgaris, Strongylus edentatus, Triodontophorus spp. and 22 species of small strongyles. Moxidectin was also 100% efficacious against larvae of Strongylus edentatus and Oxyuris equi, greater than 94% efficacious against Strongylus vulgaris larvae and Oxyuris equi adults at 14 days post-treatment. Moxidectin proved highly efficacious against luminal small strongyle larvae (> 99.9% against L4 and > 92% against L3) and moxidectin demonstrated some efficacy against encysted small strongyle larvae as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Dose titration of moxidectin oral gel against migrating Strongylus vulgaris and Parascaris equorum larvae in pony foals.

Moxidectin was tested for efficacy in ponies against experimental infections of 56 day Strongylus vulgaris larvae and 11 day Parascaris equorum larvae. Three dosages of moxidectin were tested: 300 micrograms per kg live body weight, 400 micrograms per kg, and 500 micrograms per kg, and the vehicle served as control. Ponies were first infected with 600 S. vulgaris third-stage larvae (L3) on Experiment Day 0 and then with 3000 embryonated P. equorum eggs on Day 45. Moxidectin treatments were administered on Day 56 and necropsy examinations were performed on Day 91. Strongylus vulgaris fourth-stage (L4) and fifth-stage (L5) larvae were recovered at necropsy from the control ponies, in dissections of the cranial mesenteric artery and its branches (L4 and L5), and recovered from nodules in the wall of the cecum and ventral colon (L5). Parascaris equorum larvae were recovered from the small intestine of control ponies. Moxidectin was highly efficacious against S. vulgaris L4 and L5 at all three doses tested (99.6-100%), and appeared to be equally efficacious against P. equorum larvae (100%); however, control ponies had low levels of P. equorum infections compared to previous experimental infections performed using identical methods. This suggests that the prior S. vulgaris infection on Day 0 may have influenced the subsequent experimental P. equorum infection on Day 45 and contributed to the lower recovery.

Administration, Topical↗
PubMed1995

Bovine somatotropin dose titration in lactating dairy ewes. 1. Milk yield and milk composition.

Seventy-four lactating dairy ewes were injected with recombinant bST (sometribove) in a sustained-release formulation. Ewes received 0, 80, 160, or 240 mg of bST every 14 d from wk 3 to 8 of lactation (part 1) and 0, 80, or 160 mg of bST every 14 d from wk 11 to 23 of lactation (part 2). Sometribove increased milk yield over that of the controls for all treatment groups. The increase was largest for the group that was administered 160 mg of bST: milk yield was 34.1 and 53.2% and 6% FCM was 36.9 and 51.8% for parts 1 and 2 of the study, respectively. Sometribove increased milk fat during part 1 of the study, but decreased milk fat during part 2. Protein contents of milk were decreased throughout the study. For all group, bST increased the yield of milk constituents over that of the controls. When milking frequency was reduced from twice to once daily, the difference in milk yield between control ewes and those treated with bST was maintained. Neither mastitis incidence nor milk SCC were affected by bST treatment. Recombinant bST is efficacious in increasing both actual milk yield and 6% FCM over the dose range of 80 to 240 mg/14 d without adverse effects for lactating ewes.

Animals↗
PubMed2001

Bovine somatotropin dose titration in lactating dairy ewes. 3. Treatment interval.

Seventy-four lactating dairy ewes were injected with recombinant bovine somatotropin (bST; sometribove) in a sustained-release formulation. Ewes received 0, 80, 160, or 240 mg of bST/14 d at the end of 2, 4, and 6 wk postlambing, after which injections were withheld for a 28-d period. Response of milk production to bST presented a positive linear contrast and a negative quadratic contrast. After the final injection of bST (d 0), an increase in daily milk production was observed until d +9. A continuous decrease followed with milk production returned to control levels on d +11, +18, and +20, for 80, 160, and 240 mg of bST/14 d. Milk protein content decreased gradually until d +8 before it returned to control levels on d +12, +14 and +14, for 80, 160, and 240 mg of bST/14 d. Levels of bST and IGF-I in plasma presented positive and highly significant linear contrasts and negative quadratics which were significant only for bST. Relative to the evolution of milk production, the evolution of IGF-I levels in plasma was more similar than that of bST, although the correlation of each measure with milk production was high and highly significant. It was concluded that the period between successive injections should be shorter the lower the dose employed; however, a 14-d period seemed to correspond correctly for the dosages and hormone formulation tested.

Animals↗
PubMed1993

A multicenter, randomized, double-blind, placebo-controlled, dose-titration study of oral pilocarpine for treatment of radiation-induced xerostomia in head and neck cancer patients.

PURPOSE: To determine the efficacy and safety of pilocarpine hydrochloride for symptomatic relief of postradiation xerostomia symptoms and for saliva production in patients with head and neck cancer. PATIENTS AND METHODS: One hundred sixty-two head and neck cancer patients who had received at least 40 Gy of radiation (117 patients had received > 60 Gy) with clinically significant xerostomia were enrolled onto a randomized, double-blind, placebo-controlled, multi-center clinical investigation. Patients received 2.5-mg tablets for the first 4 weeks, 5.0-mg tablets for the second 4 weeks, and 10.0-mg tablets for the last 4 weeks of the 12-week study. Patients were allowed to titrate pilocarpine or placebo for improvement in symptoms or to reduce side effects. Patients were evaluated for symptomatic relief by questionnaires and visual analog scales (VAS), and for saliva production by sialometry. RESULTS: Pilocarpine produced a significant improvement (P = .035) in overall global assessments compared with placebo. There was a statistically significant (P = .020) decreased use of oral comfort agents such as artificial saliva, hard candy, and water. Values for symptomatic improvement in dryness approached significance (P = .057). There were statistically significant postdose improvements in whole and parotid salivary flow in pilocarpine treatment groups versus placebo. All pilocarpine dosages tested were judged to be safe. Adverse experiences were primarily sweating, rhinitis, headache, nausea, and urinary frequency, with the most common side effect being mild to moderate sweating. There were no serious drug-related adverse experiences in any of the pilocarpine treatment groups. CONCLUSION: It is concluded that pilocarpine produces clinically significant benefits for the symptomatic treatment of postradiation xerostomia. Best results were obtained with continuous treatment for 8 to 12 weeks with doses greater than 2.5 mg three times per day.

Administration, Oral↗
PubMed1996

Hemodynamic effects of spinal anesthesia in the elderly: single dose versus titration through a catheter.

Sixty elderly patients (> 70 yr old) undergoing surgery for hip fracture were prospectively studied in order to compare hemodynamic tolerance of titrated doses of hyperbaric bupivacaine using continuous spinal anesthesia (CSA) versus single-dose spinal anesthesia (SDSA). Patients were randomized into two groups (CSA group: n = 30; SDSA group: n = 30). The SDSA patients received 10-15 mg of 0.5% hyperbaric bupivacaine (based on age and height), and the CSA patients received a starting dose of 5 mg of 0.5% hyperbaric bupivacaine, followed after 15 min by optional reinjection of 2.5 mg every 5 min until a T10 level sensory block was reached. Onset of anesthesia, noninvasive hemodynamic variables and the need for ephedrine were studied for 4 h after induction of anesthesia. Spinal anesthesia was successful in all patients. Decreases in mean arterial pressure were significantly less frequent and less pronounced in the CSA group (19.9% +/- 1.6% of the baseline value) than in the SDSA group (40.2% +/- 1.9%, P < 0.0001). The mean dose of ephedrine was significantly less in the CSA group (1.8 +/- 0.7 mg, administered to only 37% of patients) than in the SDSA group (19.4 +/- 3.3 mg administered to all patients, P < 0.0001). No late complications related to the spinal anesthesia technique were observed in either group. We concluded that CSA, using small titrated doses of 0.5% hyperbaric bupivacaine, is safe, efficient, and provides better hemodynamic stability than SDSA in elderly patients.

Aged↗
PubMedDate not supplied

Dose-titration to confirm the level of fenbendazole for control of Raillietina cesticillus in broiler chickens.

A total of 452 broiler chickens, naturally infected with Raillietina cesticillus, were allotted into six treatment groups. One group was fed unmedicated broiler ration (Group 1), and the other five groups were fed broiler ration containing fenbendazole at 180 ppm for 3 days (38.5 mg/kg body weight [BW]), 240 ppm for 3 days (50.9 mg/kg BW), 120 ppm for 6 days (52.2 mg/kg BW), 180 ppm for 6 days (79.9 mg/kg BW), or 240 ppm for 6 days (104.3 mg/kg BW). Fenbendazole was 100.0% efficacious against R. cesticillus when administered in the diet at 240 ppm for 6 days; 99.9% at 240 ppm for 3 days and at 180 ppm for 6 days; 99.5% at 120 ppm for 6 days; and 96.9% at 180 ppm for 3 days. Fenbendazole treatment had no adverse effect on weight gain or feed intake.

Animals↗
PubMed2001

Open-label dose-titration safety and efficacy study of tizanidine hydrochloride in the treatment of spasticity associated with chronic stroke.

BACKGROUND AND PURPOSE: Spasticity is a frequently observed motor impairment that develops after stroke; it can cause pain and disability in those affected. The objective of the present study was to evaluate the safety and efficacy of tizanidine, a centrally acting alpha(2)-adrenergic agonist, in the treatment of stroke-related spasticity. METHODS: Forty-seven patients, who were a minimum of 6 months poststroke and had significant spasticity, were studied at 4 centers. Tizanidine was administered in an open-label manner for 16 weeks, beginning at 2 mg/d and slowly titrated to a maximum of 36 mg/d. The Modified Ashworth Scale, muscle strength testing, functional assessments, and Pain and Functional Spasticity Questionnaires were administered at baseline and at 4, 8, 16, and 18 weeks (after 1 week off tizanidine). RESULTS: Spasticity was significantly improved between baseline and week 16, with a decrease in total upper extremity Modified Ashworth Scale score of 2.80+/-0.47 (P<0.0001). No decline in strength was noted. Treatment with tizanidine resulted in a significant improvement in pain intensity (P=0.0375), quality of life (P=0.0001), and physician assessment of disability (P=0.0001). The most frequent side effects were somnolence (62%) and dizziness (32%). No serious adverse events were considered to be drug related. Ten of 47 patients (21%) were able to reach the maximum daily dosage of 36 mg. CONCLUSIONS: Overall, the data suggest that tizanidine is safe and efficacious in the treatment of stroke-related spasticity, preserving muscle strength while reducing muscle tone and painful spasms in affected patients.

Clonidine↗