The possible human hazard of the naturally occurring bracken carcinogen.
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Biomedical subjects
Publications and source records attributed to D L Jones.
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Ouabain, tetrodotoxin, and calcium selective ionophore (A23187) were administered bilaterally into the hypothalamus of the unrestrained, fully conscious cat, while body temperature and other indicators of thermoregulatory responses were monitored continuously. Posterior hypothalamic microinjection of 2.0 to 10.0 ng or tissue perfusion with 1.1 X 10(-7) to 1.1 X 10(-8) M ouabain elicited dose dependent increases in body temperature accompanied by pinnae vasoconstriction, shivering and postural changes consistent with heat conservation. Tetrodotoxin, microinjected in doses of 0.5 and 5.0 ng or tissue perfusions with 7.8 X 10(-9) to 7.8 X 10(-7) M in the posterior hypothalamus elicited dose dependent falls in body temperature. However, tetrodotoxin microinjected into the anterior hypothalamic region elicited only increases in temperature. The calcium selective ionophore, A23187, at least at the concentrations used in this study, did not appear to produce any consistent effects on thermoregulation. These data support the hypothesis that the ionic milieu of the posterior hypothalamic region is essential in the maintenance of body temperature. Further, they suggest that increasing the [Ca++]/[Na+] acts in a manner similar to a depression in the firing frequency of a distinct population of cells, which may in turn determine in some way the "set-point" for body temperature. There is no evidence to support the concept that increasing the [Ca++]/[Na+] causes an increased release of the synaptic contents of the region.
Changes in synovial fluid and clinical variables after arthroscopic partial synovectomy of the middle carpal joint were studied in 12 normal horses. A 7 mm motorized synovial resector was inserted into each middle carpal joint; one middle carpal joint of each horse was randomly selected to have arthroscopic synovectomy (treated) and the opposite joint was lavaged (control). Lameness examinations and synovial fluid analyses were performed before operation and at 8, 14, 21, and 28 days after operation. Lameness variables did not differ between treated and control legs. Middle carpal and carpometacarpal joint circumference measurements were increased for 4 weeks. Synovial fluid specific gravity, pH, total protein, albumin concentration, and alpha-1-, beta- and gamma-globulin concentrations, at 8 and 14 days were significantly higher than before operation in both treated and control middle carpal joints. No significant differences were found between treated and control middle carpal joints at any time for color, clarity, pH, mucin clot formation, total protein, albumin, and globulin fractions. Arthroscopic partial synovectomy and lavage did not cause significant lameness and resulted in a synovitis indistinguishable from synovitis related to arthroscopic lavage alone.
Gross and microscopic effects of arthroscopic partial synovectomy on synovium and articular cartilage of middle carpal joints were studied in 15 horses. A 7-mm diameter motorized synovial resector was inserted into each middle carpal joint and arthroscopic partial synovectomy and lavage or arthroscopic lavage alone was performed. Study periods were 0 (three horses), 16 (three horses), and 30 days (six horses). No gross evidence of degenerative joint disease was observed at day 16 or 30. At 30 days, resected areas lacked villi and there was deposition of fibrin on the synovial surface with varying amounts of newly formed fibrovascular tissue. Thirty days after arthroscopic synovectomy, normal synovium had not formed in equine middle carpal joints.
Noradrenergic input to the hypothalamus is implicated in cardiovascular and behavioral regulation. The hypothalamus also contains high concentrations of neuropeptide Y (NPY), which often is colocalized in noradrenergic neurons. Systemically, NPY has been demonstrated to act synergistically with norepinephrine. Injections of concentrated solutions of NPY into the cerebral ventricles or hypothalamus have been found to alter ingestive behaviours, but the role of NPY in cardiovascular regulation is unknown. The objectives of this study were to determine if NPY injected directly into the hypothalamus elicits cardiovascular responses and (or) if the simultaneous administration of NPY with norepinephrine alters the cardiovascular responses elicited by norepinephrine alone. The hypothalamus of the urethane-anesthetized rat was mapped for heart rate and blood pressure responses to injections of one of the following: saline; NPY (1.9 or 0.6 pmol per injection site); norepinephrine (24, 81, or 243 nmol per injection site); or the combination of norepinephrine plus NPY. Site and drug selection were randomized. Injections of 0.25 microL were at 1.0 microL/min, bilaterally for bilateral structures and unilaterally for midline structures. Norepinephrine routinely elicited dose-dependent increases in blood pressure with latencies of approximately 1 min, which peaked by 3-5 min, accompanied or followed by tachycardia. Saline and NPY injections alone elicited no significant responses in any site. When NPY was injected together with norepinephrine, there were no significant alterations in cardiovascular variables except for attenuation of pressor responses when NPY was injected into the preoptic region and attenuation of tachycardia when NPY was injected into the caudal hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)
Dissolved organic nitrogen (DON) has been hypothesized to play a major role in N cycling in a variety of ecosystems. Our aim was to assess the seasonal and concentration relationships between dissolved organic carbon (DOC), DON, and NO3- within 102 streams and 16 lakes within catchments of differing complexity situated in Wales. Further, we aimed to assess whether patterns of land use, soil type, and vegetation gave consistent trends in DON and dissolved inorganic nitrogen (DIN) relationships over a diverse range of catchments. Our results reinforce that DON constitutes a significant component of the total dissolved N pool typically representing 40 to 50% of the total N in streams and lakes but sometimes representing greater than 85% of the total dissolved N. Generally, the levels of DON were inversely correlated with the concentration of DIN. In contrast to DIN concentrations, which showed distinct seasonality, DON showed no consistent seasonal trend. We hypothesize that this reflects differences in the bioavailability of these two N types. The amount of DON, DOC, and DIN was significantly related to soil type with higher DON export from Histosol-dominated catchments in comparison with Spodosol-dominated watersheds. Vegetation cover also had a significant effect on DON concentrations independent of soil type with a nearly twofold decrease in DON export from forested catchments in comparison with nonforested watersheds. Due to the diversity in catchment DON behavior, we speculate that this will limit the adoption of DON as a broad-scale indicator of catchment condition for use in monitoring and assessment programs.
The influence of epicardial electrode surface area and implant site on sequential pulse defibrillation threshold was investigated in four isolated heart preparations. Electrodes with surface areas of 2.5, 5.0, and 10.0 cm2 were each sutured, in random order, to the epicardial surface of the isolated heart at each of four sites: mid-ventral left ventricle (LV); mid-dorsal LV; lateral-apical LV; and lateral-basal LV. The epicardial electrode is one of the electrodes in a three-electrode, two-current pathway, sequential pulse system. The first two electrodes, which are catheter-mounted, are located in the right ventricular apex (RVA) and superior vena cava (SVC). In sequential pulse defibrillation, one shock is delivered from the SVC to the RVA, followed 1 msec later by a second shock delivered from the third electrode to the RVA. Sequential pulse defibrillation threshold was obtained with each epicardial electrode used at each site. A single-pulse (SVC to RVA) catheter threshold was also obtained in each heart. The overall mean sequential pulse threshold was 47 per cent less than the mean single-pulse threshold (P less than 0.001). Increasing patch size reduced sequential pulse threshold (P less than 0.03), but no significant effect of patch location could be demonstrated. It is concluded that sequential pulse defibrillation is superior to single-pulse catheter defibrillation and that increasing epicardial patch size is advantageous, although patch location does not influence thresholds in the isolated heart.
The time course of recovery following a brief exposure to 50% N(2)O in O(2) was assessed using a standard psychomotor test, a subjective ranking of experimental pain, and somatosensory evoked potential recordings. Results of this study suggest that recovery from a brief N(2)O exposure may be prolonged and conventional methods of assessing recovery from CNS active drugs like N(2)O may be inadequate.
A number of intraoperative anaphylactic reactions to latex occur in pediatric patients. To determine the frequency and characteristics of latex reactions in pediatric dental patients, a 32-item survey was completed by consenting parental interview at three pediatric dental clinics. Two were hospital-based, specializing in dental care for chronically ill or disabled children. The other was a dental school clinic. A total of 290 surveys were completed, in approximately equal numbers from each of the three clinics. Of the total, 2.7% reported a history of adverse reactions to latex contact. All adverse reactions were reported from the two hospital-based clinics. The rate from the hospital-based clinic specializing in the care of orthopedic and neurologically compromised children (Texas Scottish Rite Hospital, Dallas, TX) was 5.7%. The rate reported from the hospital-based clinic for chronically ill children (Children's Medical Center, Dallas, TX) was 2.0%. A history of eczema, a familial history of allergies, and a history of multiple surgical procedures were significantly more common (P < 0.05) in the population reporting adverse reactions to latex. No adverse latex reactions were reported in the one-third of the pediatric population described as normal, healthy children. Adverse reactions were more common in medically compromised children, particularly those with histories of spina bifida and/or multiple surgical procedures.
Abbott-72517 is an inhibitor of human renin and is being investigated for the treatment of hypertension. It is an orally bioavailable candidate which is being developed for oral as well as intravenous use. The preclinical development of this molecule involved studies to evaluate irritation at the site of injection in an animal model. Several formulation variables such as drug concentration, types of buffer (citrate or acetate), addition of cosolvent (ethanol) to enhance drug solubility, and tonicity modifiers such as glycerin or mannitol were evaluated. Additionally, in vitro formulation--whole blood hemolysis and plasma precipitation studies were conducted. Based on these studies, a liquid formulation containing 1.2 mg/mL Abbott-72517.HCl as base, 0.01M citrate buffer, pH 3.7, in 0.45% sodium chloride containing 2.5% mannitol was recommended for preclinical studies. Various processing and administration parameters were evaluated including filter qualification and compatibility of the drug with typical infusion fluids and administration sets. The liquid formulation was further characterized for physical and chemical stability. It was shown that it has acceptable stability at ambient temperature. Based on the accelerated temperature storage results, T90 at 25 degrees C is > 1 year for the ready-to-use liquid formulation. Additionally, a lyophilized version of the liquid formulation was evaluated.
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