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Biomedical subjects

G S Foster

Publications and source records attributed to G S Foster.

18 recordsLinked to original sources

Safety and efficacy of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. multicenter phase III clinical trials (safety).

The short-term safety of mangafodipir trisodium (MnDPDP) injection was studied in 546 adults with known or suspected focal liver lesions. An initial contrast-enhanced computed tomography examination was followed by unenhanced magnetic resonance imaging (MRI), injection of MnDPDP (5 micromol/kg), and enhanced MRI. Adverse events were reported for 23% of the patients; most were mild to moderate in intensity, did not require treatment, and were not drug related. The most commonly reported adverse events were nausea (7%) and headache (4%). The incidence of serious adverse events was low (nine events in six patients) and not drug related. Injection-associated discomfort was reported for 69% of the patients, and the most commonly reported discomforts included heat (49%) and flushing (33%). Changes in laboratory values and vital signs were generally transient, were not clinically significant, and did not require treatment. There were no clinically significant short-term risks from exposure to MnDPDP.

Abdominal Pain↗

A multisite phase III study of the safety and efficacy of a new manganese chloride-based gastrointestinal contrast agent for MRI of the abdomen and pelvis.

The purpose of this study was to evaluate the safety and efficacy of a manganese chloride-based oral magnetic resonance (MR) contrast agent during a Phase III multisite clinical trial. Two hundred seventeen patients were enrolled who were already scheduled for MRI of the abdomen and/or pelvis. In this group of patients, it was postulated that the use of an oral agent would better allow discrimination of pathology from bowel. Patients with known gastrointestinal pathology including peptic ulcer disease, inflammatory bowel disease, obstruction, or perforation were excluded to minimize confounding variables that could affect the safety assessment. Of these 217 patients, 18 received up to 900 mL of placebo, and 199 patients were given up to 900 mL of a manganese chloride-based oral contrast agent, LumenHance (Bracco Diagnostics, Inc.). Safety was determined by comparing pre- and post-dose physical examinations, vital signs, and laboratory examinations and by documenting adverse events. Efficacy was assessed by unblinded site investigators and two blinded reviewers who compared pre- and post-dose T1- and T2-weighted MRI scans of the abdomen and/or pelvis. In 111 (57%) of the 195 cases evaluated for efficacy by site investigators (unblinded readers), MRI after LumenHance provided additional diagnostic information. Increased information was found by two blinded readers in 52% and 51% of patients, respectively. In 44/195 cases (23%) unblinded readers felt the additional information would have changed patient diagnosis and in 50 patients (26%), it would have changed management and/or therapy. Potential changes in patient diagnosis or management/therapy were seen by the two blinded readers in 8-20% of patients. No clinically significant post-dose laboratory changes were seen. Forty-eight patients (24%) receiving LumenHance and four patients (22%) receiving placebo experienced one or more adverse events. Gastrointestinal tract side effects were most common, seen in 29 (15%) of LumenHance patients and in 3 (17%) of the placebo patients. LumenHance is a safe and efficacious oral gastrointestinal contrast agent for MRI of the abdomen and pelvis.

Abdomen↗

Adenomyosis: specificity of 5 mm as the maximum normal uterine junctional zone thickness in MR images.

OBJECTIVE: Our objective was to investigate the specificity of the criterion stating that a diagnosis of adenomyosis can be made confidently from MR images of the uterus when the junctional zone is thicker than 5 mm. SUBJECTS AND METHODS: Twenty clinically normal women volunteers (chosen by strict criteria) underwent MR imaging of the uterus. Images were independently evaluated by two experienced observers who measured the greatest thickness of the junctional zone in the anterior, posterior, right and left walls of the uterine corpus and at the top of the fundus. RESULTS: The mean value of the greatest junctional zone thickness (averaged for both observers) was 4.4 +/- 2.1 mm (mean +/- SD, range, 1-9 mm) for the anterior and posterior walls of the corpus, 4.3 +/- 2.1 mm (range, 1-10 mm) for the right and left walls, and 2.3 +/- 1.1 mm (range, 1-5 mm) for the fundus. At least one region of the junctional zone was found to be thicker than 5 mm by at least one observer in 13 (65%) of the 20 subjects; at least one region was found to be thicker than 5 mm by both observers in eight (40%) subjects. At least two regions were measured as thicker than 5 mm by both observers in six (30%) subjects. Serial studies of three volunteers showed transient irregular focal or diffuse thickening (up to 12 mm) of the junctional zone and focal myometrial bulging, probably due to myometrial contractions. CONCLUSION: Our results suggest that if a diagnosis of adenomyosis is based solely on junctional zone thickness in MR images, 5 mm should not be assumed as the upper limit of normal, because this assumption may result in a high false-positive rate.

Adolescent↗

Efficacy of Pasteurella haemolytica subunit antigens in a goat model of pasteurellosis.

The effectiveness of Pasteurella haemolytica biovar A, serovar 1 (Ph1) subunit vaccines was tested in goats, using challenge exposure by transthoracic injection. Twenty-two weanling male Spanish goats were randomly allotted to 4 groups. Six goats were given 2 transthoracic injections into the lung 18 days apart with live Ph1 impregnated in agar beads (positive controls). Six goats were not given injections (negative controls). Five goats were given 2 transthoracic injections into the lung 18 days apart with 4.6 mg of cytotoxin in agar beads. The remaining 5 goats were given 2 IM injections, 18 days apart, into the thigh with 4.6 mg of cytotoxin emulsified in incomplete Freund's adjuvant. Twenty-four days after the second injection, all goats were challenge-exposed to live Ph1 by transthoracic injection into the lung, and 4 days later, all goats were euthanatized and necropsied. Serum neutralizing anticytotoxin titer was measured throughout the experiment. Mean volume of consolidated lung tissue was 0.38 cm3 for the positive control group, 32 cm3 for the negative control group; 19 cm3 for the cytotoxin-lung group; and 88 cm3 for the cytotoxin-adjuvant-IM group. Only the positive control group was protected from Ph1 challenge exposure. The Ph1 cytotoxin subunit vaccine alone appeared to be ineffective, and the anticytotoxin titer was not correlated with protection. In a separate trial, 32 weanling male Spanish goats were randomly allotted to 5 groups. Each was given 2 transthoracic injections into the lung 22 days apart. Six goats were given Ph1 cytotoxin impregnated into agar beads; 6 were given Ph1 lipopolysaccharide impregnated in agar beads; 6 were given Ph1 capsule impregnated in agar beads. Six goats were given agar beads only (negative controls), and 6 were given live Ph1 impregnated into agar beads (positive controls). Twenty days after the second injection, all goats were challenge-exposed to live Ph1 by transthoracic injection into the lung, and 4 days later, all goats were euthanatized and necropsied. Mean volume of consolidated lung tissue was 0.14 cm3 for the positive control group, 7.59 cm3 for the negative control group, 11.21 cm3 for the cytotoxin group, 10.19 cm3 for the lipopolysaccharide group, and 1.6 cm3 for the capsule group. Again, only injection of live Ph1 (positive controls) induced solid protection; however, the capsule subunit vaccine induced partial protection against challenge exposure in this trial. Lipopolysaccharide and cytotoxin subunit vaccines were ineffective in protecting goats against challenge exposure with live Ph1.

Animals↗

Combined enzyme and antimicrobial susceptibility profiles of caprine Pasteurella haemolytica serovar 2 respiratory tract isolates.

The present investigation describes a novel method of demonstrating strain diversity among Pasteurella haemolytica biovar A, serovar 2 (PhA2) nasal turbinate isolates from a flock of 32 experimental goats during a naturally occurring outbreak of pasteurellosis. After a 21 day conditioning period in a feedyard, 51 PhA2 isolates from 27 culture-positive goats were identified including 1 on day 22, 14 on day 25, 21 on day 39, and 15 on day 66. Each PhA2 isolate was evaluated for its enzyme activity against 19 substrates with a commercial semiquantitative enzyme system and for its antimicrobial susceptibility with 12 drugs, resulting in 7 different enzyme profiles and 8 different antimicrobial susceptibility profiles. A total of 14 combined enzyme and antimicrobial susceptibility profiles were produced. The same PhA2 strain was isolated from only 4 of the 12 goats with 2 PhA2 isolations, while the same PhA2 strain was isolated from only 1 of the 6 goats with 3 PhA2 isolations. The data from this investigation demonstrated that the PhA2 upper respiratory tract flora from goats is highly heterologous.

Animals↗

Identification of Pasteurella haemolytica A1 isolates from market-stressed feeder calves by use of enzyme and antimicrobial susceptibility profiles.

An epidemiologic study of Pasteurella haemolytica serovar 1 (Ph1) in market-stressed feeder calves from 7 farms in eastern Tennessee was conducted. The nasal mucus of each calf was cultured sequentially at the farm of origin (day 0), at an auction market (day 133), and at a feedyard in Texas (days 141, 148, 155, and 169). Of the 103 calves tested, 77 were culture-positive, including 1 on day 0, 1 on day 133, 20 on day 141, 57 on day 148, 50 on day 155, and 14 on day 169. From the 143 Ph1 isolates, 20 enzyme profiles were determined by use of a commercial enzyme system that detects 19 enzymatic reactions; 4 antimicrobial susceptibility profiles were obtained, using the disk-diffusion method, which evaluated susceptibility to 11 antibacterial drugs. All isolates were positive for acid phosphatase and alkaline phosphatase, but were negative for alpha-galactosidase, alpha-mannosidase, beta-glucosidase, beta-glucuronidase, cystine aminopeptidase, N-acetyl-beta-glucosaminidase, and trypsin. Other positive enzyme reactions included: leucine aminopeptidase, 140 Ph1 isolates; phosphohydrolase, 90 isolates; alpha-fucosidase, 63 isolates; esterase (C4), 59 isolates; valine aminopeptidase, 30 isolates; esterase lipase (C8), 24 isolates; beta-galactosidase, 2 isolates; and alpha-glucosidase, chymotrypsin and lipase (C14), 1 isolate each. Thirty-four Ph1 profiles were identified, using combined enzyme and antimicrobial susceptibility profiles. The data indicate that the strains isolated during the feedyard period may have been determined more by farm of origin (P < or = 0.001) than by habitation with calves from other farms while in the feedyard.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Market stress-associated changes in serum complement activity in feeder calves.

Classical hemolytic complement (C) of calves was analyzed during a protocol designed to imitate the usual market handling of feeder calves from the southeastern United States. Serum C concentrations of the calves (n = 100 x 4 years) were evaluated on their farm of origin, on arrival at an auction market, on arrival at a feedyard, and during their first 4 weeks in the feedyard. Complement concentrations (measured in CH50 units) were typically lowest at the farm of origin and highest when the calves entered the auction market 28 to 133 days later. Serum C concentrations decreased after the calves encountered the severe stresses of being in the auction market for 7 days, 24-hour truck transport (1,932 km) to the feedyard, and the first 7 days in the feedyard. The C concentrations recovered after 21 to 28 days in the feedyard. Steers had significantly (P less than or equal to 0.05) lower C concentrations than did heifers in 3 of 4 years at the farm of origin, and in 2 of 4 years at the auction market. Morbid calves had significantly (P less than or equal to 0.05) lower C values than did healthy calves on day 7 in the feedyard in 3 of 4 years. There were significant differences in C concentrations of calves from different farms of origin in each of the 4 years. There was no significant difference in C concentrations of calves that were vaccinated vs those not vaccinated with Pasteurella haemolytica.

Animals↗

Comparison of four immune variables and pulmonary lesions of goats with intrapulmonary exposure and subsequent intrathoracic challenge exposure with Pasteurella haemolytica.

A comparison of immune variables following lung sensitization with live Pasteurella haemolytica serotype 1 (Ph1)-impregnated agar beads was done in 2 separate trials. The Ph1 immune variables studied were blood bactericidal activity, serum bacteriolysis, total classical complement, and indirect hemagglutination antibody. Each trial had 16 male weanling goats: 6 controls and 10 principals. In trial 1, each goat was surgically catheterized through the trachea, then the material was deposited in a bronchus. The controls received only agar beads and the principals received agar beads impregnated with live Ph1. These goats were studied for 32 days, euthanatized, and necropsied. In trial 2, the controls were each transthoracically injected with agar beads into the left lung and the principals were similarly injected with agar beads impregnated with live Ph1. These goats were studied for 35 days, then challenge exposed transthoracically by injection of Ph1 in saline solution (1.2 x 10(7) CFU/ml) into the right lung. Four days later, they were euthanatized and necropsied. The volume of lung consolidated tissue was an excellent measure of Ph1 immunity. Principal goats generated solid protective immunity to subsequent challenge exposure because minimal or no lung consolidation was observed, whereas large volumes of lung consolidation were seen in the controls. The principal goats in trial 1 gave a weak serum indirect hemagglutination Ph1 antibody response, which was attributed to the bronchial method of depositing the Ph1. The corresponding response of the control group remained negative. The Ph1 agar beads (1 x 10(6) CFU in 0.5 ml) protected the bacteria from immediate phagocytosis and lysis as indicated by the induced pneumonic deaths of 2 principals 5 days later.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immune response to pulmonary injection of Pasteurella haemolytica-impregnated agar beads followed by transthoracic challenge exposure in goats.

A method of inducing Pasteurella haemolytica serotype 1 (Ph1) lung infection in goats, using low numbers of bacteria and without impairing host immunity, was developed. Two trials were conducted. Results of trial 1, using 10 principals (Ph1 agar beads) and 6 controls (agar beads alone), indicated that Ph1 organisms imbedded in agar beads could survive host lung defenses for 32 days. Results of trial 2 indicated that lung immunity in the inoculated goats (principals) was high and they were more protected than controls against a transthoracic challenge of Ph1 (1.18 x 10(7) colony-forming units) injected into a lung of each goat on posttreatment day 35. When comparing challenge-exposed principals with controls, the controls developed rectal temperatures above normal for a longer time, duration of anorexia was longer, and signs of depression were seen. The controls developed large areas of consolidated lung tissue, more Ph1 isolates were recovered from nasal turbinates and lung tissue, and higher Ph1 concentrations were found in the lungs. The serum Ph1 indirect hemagglutination antibody titers in the principals of both trials increased, compared with titers in controls. Principal goats in trial 2 had higher Ph1 indirect hemagglutination antibody titers after injection of Ph1-impregnated agar beads and less severe lung lesions after challenge exposure than did controls. The small pneumonic consolidated lesions in the principals, compared with extensive lesions in controls after Ph1 challenge exposure, indicated a high degree of immunity after exposure to Ph1 organisms imbedded in agar beads.

Animals↗

Preoperative imaging in primary hyperparathyroidism. Role of thallium-technetium subtraction scintigraphy.

Primary hyperparathyroidism, although often silent clinically, may lead to significant morbidity if it remains untreated. In more than 95% of all cases the cause is a parathyroid adenoma or glandular hyperplasia. Regression of disease follows successful surgical excision of the abnormal parathyroid gland. Recurrent or persistent hyperparathyroidism is most commonly caused by solitary adenomas, which may have an ectopic location. Preoperative localization of lesions may improve postoperative cure rates and decrease morbidity. Thallium T1 201 chloride-technetium Tc 99m pertechnetate subtraction scintigraphy was performed on 15 patients with primary hyperparathyroidism. The sensitivity and specificity for detection of abnormal glands were 90% and 95%, respectively. False-positive or false-negative results were minimize by strict adherence to a protocol and by the use of well-defined diagnostic criteria. Because of the superior sensitivity and specificity, this modality should be the primary imaging method of choice for preoperative evaluation of primary hyperparathyroidism. The relative role of other imaging modalities is also discussed.

Adenoma↗

Blood bactericidal assay (Pasteurella haemolytica) comparison of morbidity in marketed feeder calves.

An in vitro bactericidal assay that used bovine heparinized blood was investigated for its usefulness in detecting differences in the bactericidal immunity of calves against Pasteurella haemolytica serotype 1 (Ph1). Greater than 90% of killing occurred within 30 minutes. The substitution of fetal calf serum for autologous calf plasma caused loss of bactericidal activity of the blood. Decomplemented calf serum also was low in bactericidal activity. The blood bactericidal assay appears to be opsonin antibody-dependent and complement-dependent. The coefficient of variation (CV) that can be expected with this assay was established by use of a group of 8 calves; within-day CV maximum was 0.9, and between-day CV maximum was 2.1. The blood bactericidal assay was used to evaluate 30 calves under typical market stress from 4 farms in eastern Tennessee. All calves had decreased bactericidal activity, as they moved into a feedyard in Texas. The bactericidal activity was reduced among sick calves, based on the severity of clinical signs. Morbidity was highest during the first 14 days in the feedlot. During this period, healthy calves had a decreased bactericidal index (BI) of 4 points, and calves with clinical signs of bovine respiratory tract disease for 3 days had a decreased BI of 8 points. The average reduction in the BI of calves with clinical signs of bovine respiratory tract disease for 6 or more days was 14 points.

Animals↗

Effects of photoperiod and estradiol on tonic gonadotropins in ovariectomized ewes.

Estradiol-17 beta (estradiol) inhibition of tonic (basal, as opposed to cyclic or preovulatory) serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was evaluated in ewes subjected to long or short photoperiods. Nine mature Colombia ewes were ovariectomized early in the breeding season and implanted with either Silastic capsules containing approximately .12 g of estradiol (n = 4) or with empty capsules (n = 5). Ewes were housed indoors for 43 wk under controlled lighting: 17 wk of short days (8.5 h light: 15.5 h dark), 12 wk of long days (15.5 h light: 8.5 h dark) and a second 14 wk of short days. Five intact ewes penned with a vasectomized marker ram were used to evaluate estrus under these photoperiodic conditions. Estrous cycles in intact ewes ceased approximately 10 wk after onset of the long photoperiod and resumed approximately 11 wk after return to short days. In ovariectomized ewes, estradiol dramatically depressed FSH as well as LH during the long photoperiod and, to a lesser degree, depressed FSH, but not LH, during the short photoperiod. These data support the hypothesis that sensitivity of the tonic gonadotropin regulatory mechanism to estradiol inhibition changes with photoperiod and, thereby, modulates the onset and duration of the breeding and anestrous seasons in ewes. A model accounting for seasonal changes in the inhibitory action of estradiol is proposed.

Animals↗

Survival from acute hepatorenal syndrome following splenorenal shunt.

Acute aggravation of chronic hepatorenal syndrome following angiography is described in a patient with recovery and long-term survival following splenorenal shunt. It is believed that this patient represents a type of hepatorenal syndrome which can be expected to tolerate shunt and recover from hepatorenal syndrome. Possible mechanisms of the pathophysiology are discussed and recommendations made on this basis for the selection of such patients for portal decompression.

Acute Kidney Injury↗