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Biomedical subjects

A R Harris

Publications and source records attributed to A R Harris.

At least 19 recordsLinked to original sources
PubMed2001

Towards developing a non-SnCl2 formulation for RP444, a new radiopharmaceutical for thrombus imaging.

There are many factors influencing the yield and radiochemical purity (RCP) of the radiopharmaceutical RP444. These include heating temperature, heating time, pH, the use of a buffering agent and a bulking agent, as well as the component (XV066, tricine, TPPTS, and Na99mTcO4) concentration. Through a series of radiolabeling experiments, we found that a formulation comprised of 20 microg of XV066, 6.5 mg of tricine, 40 mg of mannitol, 5 mg of TPPTS, and 0.1 mg of Pluronic acid dissolved in 1.0 mL of 250 mM succinate buffer (pH 5.0) gives the best RCP for RP444. The formulation can be lyophilized to form a stable crystal "cake". The radiolabeling is achieved by adding 1.5 mL generator eluant (33-133 mCi of Na99mTcO4) to a lyophilized vial and heating the reaction mixture at 100 degrees C for 10 min. Using this formulation, RP444 is prepared consistently in high yield with RCP > or = 90%. Formation of [99mTc]colloid is minimal (< 0.5%).

Chromatography, High Pressure Liquid↗
PubMed2000

Solid formulations of binucleate Rhizoctonia isolates suppress Rhizoctonia solani and Pythium ultimum in potting medium.

Two isolates of binucleate Rhizoctonia spp., previously selected for efficacy in suppression of Rhizoctonia solani and Pythium spp., as well as plant growth promotion, were incorporated into various solid substrate formulations. These formulated products were assayed at three doses in three glass-house experiments for biocontrol of damping-off diseases in Capsicum annuum. R. solani anastomosis group 4 or Pythium ultimum var. sporangiiferum were incorporated into pasteurized potting medium with each formulated binucleate Rhizoctonia product. All formulations were effective against both pathogens in at least two experiments, but some formulations of one isolate of binucleate Rhizoctonia did not give consistent control of R. solani in one experiment. The most consistent formulation, which provided control of both pathogens at all doses of binucleate Rhizoctonia, was the simple substrate of rice hulls. The implications for commercialization of a biocontrol product are discussed.

Capsicum↗
PubMed1999

Biocontrol of Rhizoctonia solani and Pythium ultimum on Capsicum by Trichoderma koningii in potting medium.

Two isolates of Trichoderma koningii were evaluated for efficacy in control of damping-off diseases in seedlings of Capsicum annuum grown in pasteurized potting medium in a glasshouse. A selected isolate of binucleate Rhizoctonia and two fungicides were also included as standards for control of Rhizoctonia solani and Pythium ultimum var. sporangiiferum. Both isolates of T. koningii reduced seedling death caused by R. solani in one of two experiments, and by P. u. sporangii-ferum in two of three experiments. Neither isolate of T. koningii suppressed damping-off caused by either pathogen as consistently as the binucleate Rhizoctonia or fungicides. The implications of these results for commercial disease management are discussed.

Fungicides, Industrial↗
PubMed1999

Oral contraceptives and oral antibiotics: interactions and advice in an accident and emergency setting.

OBJECTIVE: (1) To determine what advice, if any, would be given by accident and emergency (A&E) doctors to women who were taking the combined oral contraceptive pill (OCP) if they had been issued with broad spectrum antibiotics and (2) after an audit programme had been instigated, whether appropriate advice was given to such women. METHODS: A questionnaire was circulated to 12 doctors working in the Exeter A&E department to assess their level of knowledge in prescribing antibiotics to women taking the OCP. Notes of women aged 15-50 who had been prescribed broad spectrum antibiotics were examined to see if a contraceptive history had been taken. If the patient was found to be taking the combined OCP it was noted whether documented advice had been given about using an additional form of contraception. Six months later after two education sessions had been held, prescriptions and notes were examined. A patient education leaflet was produced to be given to these women, indicating what additional precautions should be taken after having been prescribed antibiotics. SETTING: The A&E department of a busy district general hospital. SUBJECTS: Women aged 15-50 who had been issued with broad spectrum antibiotics. RESULTS: The level of knowledge in regard to contraceptive advice given to women taking the OCP among doctors working in an A&E department was poor. However, after educational sessions and the production of a patient information leaflet, there was an improvement in women receiving correct advice. CONCLUSIONS: The clinical significance of drug interactions between oral contraceptives and antibiotics indicates the importance of asking a full contraceptive drug history of any woman of childbearing age and documenting this in the notes. Regular audit of this topic is needed to keep it at the front of doctors' minds.

Accidents↗
PubMed1984

A review of schistosomiasis in immigrants in Western Australia, demonstrating the unusual longevity of Schistosoma mansoni.

Sixteen patients with imported schistosomiasis in Western Australia, a non-endemic area, are recorded. Ten with Schistosoma mansoni had lived there for over 20 years, three for over 31 years and two for more than 32 years. No record of a life span of 31 years for S. mansoni can be found in the literature. The principal symptomatology in three patients with S. mansoni was hypersplenism. Four patients with S. mansoni were asymptomatic. Ten had eosinophil counts greater than 0.3 X 10(9)/1 and one who showed no peripheral eosinophilia had numerous eosinophil myelocytes in his bone marrow. A diagnosis of schistosomiasis was initially suspected in five cases by respective discovery of eosinophil myelocytes in the bone marrow, radiological evidence of calcification of the bladder wall and beading of both ureters, cytoscopic findings of sandy patches in the bladder, discovery of ova in the wall of a fallopian tube at ectopic gestation and the presence of ova and an adult worm in a uterine leiomyoma. The risk of infection of the Ord River Dam is greater for S. japonicum than for the African species. An epidemiological feature of this series is that refugees from Poland contracted schistosomiasis (S. mansoni) in refugee camps in East Africa and then migrated to Western Australia between 1950 and 1953.

Animals↗
PubMed1984

Visible persistence as a function of viewing condition and eye-handedness relationship.

Duration of visible persistence was investigated as a function of spatial frequency, orientation and viewing condition (binocular, dominant eye and non-dominant eye). Persistence increased with increasing spatial frequency and was longer for oblique than vertical gratings. Viewing condition also influenced visible persistence such that binocular persistence was significantly shorter than for either monocular condition. A post-hoc analysis indicated that this was only true with subjects who were right-handed and right-eyed. Subjects mixed on this relationship showed no differences in persistence across viewing conditions. A second experiment which selected subjects on the basis of this relationship confirmed the results of Experiment 1. The results for the right-right group broaden the generality of the rule showing an inverse relationship between response strength and persistence duration. The results for the Mixed group indicate a lack of binocular summation.

Dominance, Cerebral↗
PubMed1982

Collagenous colitis: a case report and review of the literature.

A case of collagenous colitis is reported and the literature reviewed. The disease presents with watery diarrhea and abdominal pain in middle-aged subjects. Women predominate in the small number of reported cases. Colonic and rectal biopsies show excessive collagenization of the so-called collagen table in the superficial lamina propria. There is an associated degeneration and desquamation of the interglandular epithelial lining cells. The cause is not known but the clinical course with symptomatic treatment can wax and wane with corresponding deterioration or improvement in the biopsy features.

Adult↗
PubMed1979

The role of sulfhydryl groups on the impaired hepatic 3',3,5-triiodothyronine generation from thyroxine in the hypothyroid, starved, fetal, and neonatal rodent.

The role of nonprotein sulfhydryl groups (NPSH) in the decreased in vitro hepatic 3',3,5-triiodothyronine (T(3)) generation from thyroxine (T(4)) in the starved, hypothyroid, fetal and 1- to 4-d-old neonatal rat and dwarf mouse was assessed. NPSH were measured in fresh 25% liver homogenates prepared in 0.1 M PO(4)/10 mM EDTA buffer. As compared with values in adult male rats, NPSH concentration was decreased in the 2-d-starved (1.1+/-0.04 (mean+/-SE) vs. 2.2+/-0.15 mmol/250 g wet liver weight, P < 0.001), fetal (1.0+/-0.04 vs. 3.2+/-0.08, P < 0.001), 1-d-old neonatal (1.1+/-0.03 vs. 2.1+/-0.04, P < 0.001), and hypothyroid (thyroidectomized 60 d) (1.4+/-0.06 vs. 2.2+/-0.15 P < 0.001) rat. NPSH were also decreased in the hypothyroid, hypopituitary dwarf mouse as compared with values in their normal litter mates (1.3+/-0.03 vs. 2.0+/-0.2, P < 0.01). Chronic administration of T(3) (0.5 mug/100 g body wt per d) markedly increased hepatic T(3) generation from T(4) in the thyroidectomized rat and in the dwarf mouse to values similar to those observed in the normal rodent without affecting NPSH concentration. In contrast, T(3) administration to the starved rat did not alter either hepatic T(3) generation from T(4) or NPSH. Reduced glutathione concentration was also markedly decreased in the starved rat (fed; 1.05+/-0.075 mmol/250 g wet tissue vs. starved 0.38+/-0.02, P < 0.001). Dithiothreitol (DTT), a thiol reducing agent, increased hepatic T(3) generation from T(4) in the normal adult male rat by 45+/-5% in six experiments. When compared to DTT-stimulated control homogenates, the addition of DTT completely restored hepatic T(3) generation in starved rats, partially restored T(3) generation in 1- and 4-d-old neonates, but had little or no effect in the fetal and hypothyroid rat and dwarf mouse. Liver homogenates stored for 6 mo at -20 degrees C lost their capacity to generate T(3) from T(4). NPSH concentrations in the frozen homogenates decreased progressively with increasing storage and were absent by 6 mo. 5'-Deiodinase activity correlated with NPSH concentration in the stored homogenates (r = 0.95, P < 0.005). Addition of DTT partially restored hepatic T(3) generation in the frozen homogenate. It is concluded that NPSH are important for the action of the liver 5'-deiodinase. The decreased hepatic T(3) generation in the starved rat is associated with decreased NPSH but not with a decrease in the absolute quantity of 5'-deiodinase because provision of sulfhydryl groups restored hepatic T(3) generation to normal. In contrast, the decreased hepatic T(3) generation in the adult hypothyroid rodent and in the fetal rat is probably due to a decrease in the enzyme concentration per se. In the 1- and 4-d neonatal rat, the decrease in hepatic T(3) generation is secondary to a decrease in NPSH and the deiodinating enzyme.

Aging↗
PubMed1978

Effect of starvation on hypothalamic-pituitary-thyroid function in the rat.

Total starvation in the rat for 2 days did not alter the hypothalamic content of thyrotropin-releasing hormone (TRH), but did decrease both pituitary TSH content and serum TSH concentration. Five days starvation resulted in a significant decrease in serum TSH and a slightly enhanced serum TSH response to exogenous TRH, suggesting that the pituitary retains its sensitivity to TRH. Fasting for 5 days resulted in a decreased 1 and 4th, but an increased 24th thyroid 131I uptake. Other starvation-induced abnormalities of intrathyroid 131I metabolism were a consistent increase in the percent of organified 131I present as MIT and DIT and a decreased percent 131I labeled T4 AND T3. These alterations in the intrathyroid metabolism of 131I in the starved rat probably reflect both a decrease in serum TSH concentration and a decrease in urinary and fecal loss of administered 131I. The serum total and free T4 and total and free T3 concentrations were decreased following 2 and 5 days of starvation.

Animals↗
PubMed1978

Effect of starvation, nutriment replacement, and hypothyroidism on in vitro hepatic T4 to T3 conversion in the rat.

To evaluate the effect of starvation, oral and i.v. nutriments, and hypothyroidism on the peripheral conversion of thyroxine (T4) to 3,3', 5-triiodothyronine (T3) in the rat and mouse, an in vitro system for assessing T4 conversion to T3 by fresh liver homogenates was used. A 2-day starvation in the rat reduced hepatic T3 generation from T4 by 47% +/- 3.5% (mean +/- SE) in six separate experiments and also impaired the metabolism of 125I-r-T3. Administration of carbohydrate (CHO) and amino acids (P), but not lipid (L), significantly increased T3 generation above values observed in the starved rat. The mean serum glucose concentration was similar in all nutriment-infused groups, but serum insulin was significantly greater in the CHO- and P-infused as compared to the L-infused rats. These findings suggest that CHO and P, but not L, are important modulators of hepatic outer ring thyronine deiodination in the rat, perhaps due to increased intracellular glucose. Hypothyroidism in the rat induced by thyroidectomy and congenital secondary hypothyroidism in the dwarf mouse resulted in a striking decrease in hepatic conversion of T4 to T3. This decrease was restored to normal by the daily s.c. administration of physiologic doses of T4 (1.5 microgram/100 g) or T3 (0.5 microgram/100 g) for 14 days, and was increased above normal following treatment of normal rate with greater than physiologic doses of T4 (3microgram/100 g) or T3 (1 microgram/100g). In vitro hepatic conversion of T4 to T3 is, therefore, dependent upon thyroid function. Since 2-days starvation in the rat was associated with decreased serum concentrations of T4, T3, and TSH, and hypothyroidism resulted in decreased conversion of T4 to T3, the effect of a constant 2-day infusion of physiologic doses of T4 or T3 in the starved rat on the in vitro deiodination of T4 was assessed. Thyroid hormone replacement did not enhance the conversion of T4 to T3 in the starved rat. These observations suggest that the starvation-induced decrease in hepatic generation of T3 from T4 is not due to hypothyroidism and that the mechanism(s) of the decreased T3 production observed in starvation and hypothyroidism is different.

Amino Acids↗
PubMed1978

The physiological role of thyrotropin-releasing hormone in the regulation of thyroid-stimulating hormone and prolactin secretion in the rat.

The physiological role of thyrotropin-releasing hormone (TRH) in the regulation of thyrotropin (thyroid-stimulating hormone, TSH) and prolactin (Prl) secretion has been assumed but not proven. Stimulation of their release requires pharmacologic doses of TRH. Lesions of the hypothalamus usually induce an inhibition of TSH secretion and an increase in Prl. To determine whether TRH is essential for TSH and Prl secretion in the rat, 0.1 ml of TRH antiserum (TRH-Ab) or normal rabbit serum was administered to normal, thyroidectomized, cold-exposed, and proestrus rats through indwelling atrial catheter. Serum samples were obtained before and at frequent intervals thereafter. Serum TSH concentrations in normal, thyroidectomized, cold-exposed, and proestrus rats were not depressed in specimens obtained up to 24 h after injection of normal rabbit serum. In contrast, serum TSH was significantly decreased after the administration of TRH-Ab in all normal (basal, 41+/-8 muU/ml [mean+/-SE]; 30 min, 6+/-2; 45 min, 8+/-3; 75 min, 4+/-2); thyroidectomized (basal, 642+/-32 muU/ml; 30 min, 418+/-32; 60 min, 426+/-36; 120 min, 516+/-146); coldstressed (basal, 68+/-19 muU/ml; 30 min, 4+/-3; 180 min, 16+/-8); and proestrus (basal, 11 a.m., 57+/-10 muU/ml; 1 p.m., 20+/-3; 3 p.m., 13+/-4; 5 p.m., 19+/-3) rats. However, 0.1 ml of TRH-Ab had no effect on basal Prl concentrations in normal or thyroidectomized rats and did not prevent the Prl rise in rats exposed to cold (basal, 68+/-7 ng/ml; 15 min, 387+/-121; 30 min, 212+/-132; 60 min, 154+/-114), or the Prl surge observed on the afternoon of proestrus (basal 11 a.m., 23+/-2 ng/ml; 1 p.m., 189+/-55; 3 p.m., 1,490+/-260; 5 p.m., 1,570+/-286). These studies demonstrate that TRH is required for TSH secretion in the normal, cold-exposed and proestrus rat and contributes, at least in part, to TSH secretion in the hypothyroid rat, but is not required for Prl secretion in these states.

Animals↗
PubMed1978

"Short" loop feedback regulation of hypothalamic and brain thyrotropin-releasing hormone content in the rat and dwarf mouse.

In order to determine whether T4, TSH, or both affect hypothalamic TRH content, primary or secondary hypothyroidism was induced in the rat by thyroidectomy (Tx) or hypophysectomy (Hx), respectively. Two weeks later, rats were treated with T4, TSH, or both for 14--16 days. Tx or Hx significantly decreased hypothalamic TRH content, and T4 treatment restored hypothalamic TRH to normal in the Tx but not in the Hx rats. When TSH was administered simultaneously with T4 to Hx rats, hypothalamic TRH content was restored to normal. Whole brain TRH content was not affected by Tx, Hx, or by the various treatment regimens. Similar experiments were performed in Snell dwarf (dw/dw) mice. Hypothalamic TRH content was significantly decreased when compared to normal litter mates (dw/+). As in Hx rats, T4 administration to dw/dw mice for 16 days did not restore hypothalamic TRH content to normal. Brain TRH content was similar in both groups and was not altered by T4 treatment. It is concluded that T4 affects hypothalamic TRH content, but that TSH is required for this T4 effect. Whole brain TRH, on the other hand, is unaffected by any of these alterations in thyroid-pituitary function.

Animals↗