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Biomedical subjects

C Cunningham

Publications and source records attributed to C Cunningham.

At least 145 records · Page 8Linked to original sources
PubMed1984

Serum cyclosporin levels, hepatic drug metabolism and renal tubulotoxicity.

The present study was designed to examine inter-relationships between serum cyclosporin (CsA) levels, hepatic drug metabolising enzyme activity and CsA induced nephrotoxicity. CsA (25 mg/kg p.o.) was administered daily to male Sprague-Dawley rats: groups of animals were killed on days 0, 4, 7, 10 and 14 and thereafter at weekly intervals over the 7-week course of the experiment. Nephrotoxicity was evaluated by measuring tubular enzymuria and by light microscopy and serum CsA levels (parent drug plus certain metabolites) were determined by radioimmunoassay. The hepatic microsomal mono-oxygenase enzyme system was monitored by measurement of cytochrome P-450, aminopyrine N-demethylase and NADPH-cytochrome c reductase. Nephrotoxicity appeared within 4 days of starting treatment and continued for 4 weeks. Between weeks 4 and 6 there was a period of complete remission followed by the return of renal damage. Aminopyrine N-demethylase activity fell during the first 4 weeks. During the period of remission, however, N-demethylase activity rose to a point significantly higher than pretreatment values and serum CsA levels fell to their lowest concentration. With relapse, hepatic N-demethylase activity again fell below normal and serum drug levels rose to their pre-remission values. From the third week onward, changes in NADPH-cytochrome c reductase activity paralleled those in N-demethylase activity. The hepatic microsomal concentration of cytochrome P-450 did not, however, change significantly during the 7-week period of CsA treatment. Our results suggest that the spontaneous remission of CsA-induced nephrotoxicity is due to a reduction in circulating drug levels caused by increased hepatic CsA metabolism.

Animals↗
PubMed1984

Enhancement of high dose cyclosporin A toxicity by frusemide.

Adult Sprague-Dawley rats were given cyclosporin A (CyA), frusemide (Fr) or both drugs daily for 14 days. The doses of CyA (50 mg/kg) and Fr (5 mg/kg) were approximately 3-6 times and twice respectively those used in man. Fr on its own produced a diuresis lasting approximately 3 hr. This was characterized by a 10-fold increase in urine flow rate, a 40-fold increase in the rate of sodium excretion, and by 2- and 4-fold increases in urea and creatinine clearance rates, respectively. In addition, there was a doubling in urinary N-acetyl-beta-D-glucosaminidase (NAG) activity. After 4 days of combination treatment with CyA and Fr, the diuretic-induced increases in urine flow rate, sodium excretion and urinary NAG activity were similar to those following frusemide alone. However, urea and creatinine clearances did not increase during the diuresis. Fr itself did not impair renal function, but rats receiving only CyA did show elevations in serum urea and creatinine, with reductions in clearance rates, which progressed with time. There was also an increase in NAG enzymuria. When the two drugs were exhibited together, renal function was more severely impaired. All animals given CyA showed proximal renal tubular cell vacuolation: in half the damage was confined to the straight segment, while the rest showed additional severe convoluted segment change. Renal function was most abnormal in those rats in which both segments were affected. All animals given both drugs showed both straight and convoluted tubular abnormalities and a 2-fold increase in serum CyA levels. CyA-induced disturbances in hepatic function and lymphoid tissue atrophy were unaffected by the addition of Fr, nor did Fr affect the immunosuppressive action of CyA.

Acetylglucosaminidase↗
PubMed1984

Detection of a 16S rRNA . initiator-tRNA complex by a new selective labelling method.

Cupric-ion induced hydrolysis of [35S]Met-tRNA but not of N-formyl-Met-tRNAMetf permitted the specific terminal labelling of initiator tRNA. Initiator tRNA, labeled in this way, was suitable for sequence analysis without the need for further purification. By probing labeled initiator tRNA with specific RNases, changes in this molecule during its interaction with the 30S particle or with 16S rRNA were investigated. Initiation complexes were resistant to the action of single-strand, base-specific nucleases Bc and Phy M and, except for one base of the anticodon stem, were also resistant to digestion by the double-strand-specific V1 nuclease of Naja venom. In contrast, T1 RNase digestion of the initiator tRNA in the presence of 16S rRNA enhanced cleavage of bases in the T stem of the molecule.

Base Sequence↗
PubMed1983

Renal cadmium content in the West of Scotland.

The trace element content of kidneys has been documented in very few international centres. Significant differences can be demonstrated between the cortical and medullary levels of calcium, zinc and cadmium. For the West of Scotland the values for the latter are similar to those found in Scandinavia. There are significantly higher cadmium contents in subjects who smoke and who have evidence of ischaemic heart disease.

Adolescent↗
PubMed1983

Chemical restraint of wild horses: effects on reproduction and social structure.

Twenty-three (9 male, 14 female) wild horses (Equus caballus) in the Great Basin Desert were immobilized by ground techniques with succinylcholine chloride during 1,950 person-hr. Induction (means = 2.09 +/- 0.59 min) and recovery (means = 12.4 +/- 5.0 min) were rapid and most animals were returned in less than 10 min to original bands. Dosages ranged from 0.66-0.77 mg/kg body weight and neither abortions nor band changes in group membership resulted. However, a few concerted efforts up to 24 hr were needed to return some animals to original bands and three non-drug related mortalities occurred. The responses of bands to darted members and the overall influence of the operation on reproduction, movements, and social structure are presented.

Animals↗
PubMed1982

The importance of cadmium as a factor in calcified upper urinary tract stone disease--a prospective 7-year study.

The non-essential trace metal cadmium may cause major pathological effects on the kidneys. A group of coppersmiths who have been chronically exposed to cadmium poisoning was systematically studied over a 6-year period. The stone prevalence in the group is now just under 40% as compared with 3.5% in a general population. The blood cadmium levels have remained persistently elevated despite removal of the cadmium source. The measurement of cadmium as a means of monitoring chronic poisoning has been undertaken in terms of the prospective study in the coppersmiths and also in its relationship to other trace metals, namely serum zinc and copper. Urologists should be aware of the possibility of cadmium poisoning.

Cadmium↗
PubMed1982

Studies of lead and cadmium exposure in Glasgow, U.K.

Domestic water and whole blood samples were collected early in 1981 from two hundred volunteers living in the Glasgow area of Scotland, U.K. The concentration of lead in the water and blood samples, and of cadmium in the blood, was measured. The blood lead and cadmium concentrations were compared to those obtained in the Survey of 1979. There has been a fall in blood lead concentrations since the 1979 Survey. In contrast, the blood cadmium levels had remained similar. This diminution in blood lead concentration is attributed to a fall in water lead concentration caused by raising the pH of the water supply in the Glasgow area. The main determinant for cadmium in blood appears to be cigarette smoking habits, which had not changed.

Adolescent↗
PubMed1981

Sibling groups. Interaction with siblings of oncology patients.

Siblings of pediatric oncology patients in active therapy met as a group for 5 consecutive weeks with two oncology team members. The parents met simultaneously in another location in the hospital. The goals were to provide (1) a support group for the siblings, (2) information regarding the various treatment regimens, and (3) specific knowledge regarding the particular stresses of specific therapy programs. The following problem areas were identified: (1) reiteration of resentment toward the patient due to the amount of attention focused on them by family and friends, (2) embarrassment in talking about the patient's illness, and (3) the relationship between the parent's willingness to discuss the patient's illness at home and the sibling's comprehension of the illness.

Child↗
PubMed1977

Problems in diagnosis and management of children with cerebral palsy and deafness.

Problems in the diagnosis, management and educational placement of 10 children with cerebral palsy and deafness are reported. Serious inadequacies revealed by the study include delays in diagnosis, poor co-ordination of decision-making between services and frequent changes of school--all leading to unsatisfactory progress by these children.

Adolescent↗