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Biomedical subjects

T W Poole

Publications and source records attributed to T W Poole.

At least 19 recordsLinked to original sources

Effect of oral cyclosporin on renal function in Crohn's disease.

Twenty-one patients with Crohn's disease were followed prospectively for 24 weeks to examine the effect of a low-dose cyclosporin regime on renal function (initial dose 5 mg/kg reduced by 1 mg/kg every two months to a maintenance of 2 mg/kg). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by radioisotope clearance at 0, 6 and 24 weeks. GFR and ERPF fell significantly (mean GFR at baseline: 120.9 ml/min/1.73 m2; at six weeks: 100.9 ml/min/1.73 m2; mean ERPF at baseline: 497.3 ml/min/1.73 m2; at six weeks: 398.5 ml/min/1.73 m2). Following dose reduction, the ERPF remained lower than baseline (mean 408.6 ml/min/1.73 m2), and there was a trend towards the GFR remaining low (mean 111.8 ml/min/1.73 m2). Serum creatinine rose significantly (median pretreatment 72 mumol/liter; median at four weeks 86 mumol/liter) but returned to baseline after dose reduction. Plasma cyclosporin levels and serum creatinine did not help predict the extent of changes in renal function. At low doses, cyclosporin causes changes in renal hemodynamics that may not be reversed by dose reduction.

Administration, Oral↗

Long-term treatment of Crohn's disease with cyclosporine: the effect of a very low dose on maintenance of remission.

Low-dose oral cyclosporine was used to maintain remission in patients with Crohn's disease. In seven patients, cyclosporine was used as a steroid-sparing agent; in 14 it was given for refractory active disease as an adjunct to conventional treatment, and then continued as maintenance treatment. Cyclosporine was given at an initial dose of 5 mg/kg reduced by 1 mg/kg at 2-month intervals until a maintenance dose of 2 mg/kg was reached. Of the seven patients in whom cyclosporine was used as a steroid-sparing agent, six had a relapse. Remission was achieved in seven of the refractory active group, but cyclosporine was withdrawn because of side effects in six of the patients in this group. Of the seven patients who had achieved remission, six subsequently had a relapse. Therefore, 12 of 14 patients (86%) in remission had a relapse despite cyclosporine maintenance. Ten of these (83%) had a relapse at a cyclosporine dose of 2 or 3 mg/kg. Cyclosporine levels at relapse (median, 74 ng/ml) were lower than the mean levels over the first 6 weeks of treatment (median, 130 ng/ml; p = 0.02). Our data do not support the use of cyclosporine to maintain remission in Crohn's disease.

Administration, Oral↗

Studies on the degranulation test for carcinogens.

The radiometric assay of degranulation of the hepatic endoplasmic reticulum by chemical carcinogens has been re-examined. Both 1,2,3,4,- and 1,25,6-dibenzanthracenes caused degranulation of rough membranes in vitro; with acetamidofluorenes and naphthylamines the carcinogenic analogues caused moderately greater degranulation. Degranulation by 1,2,3,4-dibenzantracene was rapid and was maximal after 5 min incubation. Pretreatment of animals with phenobarbital or methylcholanthrene increased the fraction of rough membranes, but these were not fully granulated. The assay is limited in specificity and sensitivity because the 1.35 M sucrose gradient does not effectively separate rough and smooth membranes, and sedimented membranes are contaminated with aggregates of free ribosomes.

1-Naphthylamine↗

[Steroid-free treatment of renal transplant patients with cyclosporin A. A European multicentre study].

In a multicentre trial conducted in eight European centres, 232 recipients of cadaveric renal allografts were randomly allocated to receive either cyclosporin A (CyA, 117 patients) or azathioprine and steroids (control, 115 patients) for immunosuppression. After a follow-up period of up to eleven months, graft survival probability estimates are 73% in the CyA group and 53% in the control group. Two deaths have occurred In the CyA group and seven in the control group. 82% of the CyA group with functioning grafts are receiving CyA alone, 17% have been changed to azathioprine and steroids and one patient is receiving prednisolone in addition to CyA; 27% have never received steroids. At six months post-transplant renal function is similar in patients receiving CyA and in those receiving azathioprine and steroids. On the basis of these preliminary results CyA appears to be more effective than conventional immunosuppression and avoids the necessity of long-term steroid therapy.

Adult↗

The agouti suppressor (As) coat color mutation in mice: developmental effects on the expression of agouti locus alleles.

The alleles at the agouti locus in the mouse determine whether eumelanin or pheomelanin is synthesized by the follicular melanocytes. The agouti suppressor (As) mutation, which is closely linked to the agouti locus, reduces the amount of pheomelanin produced by whatever agouti alleles are present in the animal's genome. Previous developmental studies have indicated that the agouti alleles exert their influence on the follicular melanocytes via interactions between the developing dermis and epidermis. Using the techniques of dermal-epidermal recombination of embryonic agouti suppressor (AsAw/AsAw), white-bellied agouti (Aw/Aw), yellow (Ay/a), viable yellow (Avy/Avy), black and tan (at/at), and nonagouti (a/a) mouse skin, the present study demonstrates that 1) the dermis is responsible for the development of regional pigmentation patterns in white-bellied agouti mice, and 2) the agouti suppressor mutation interferes with the expression of the white-bellied agouti allele by acting on the dermis as well as the epidermis. In addition, this study provides further evidence for the role of the epidermis in the expression of the agouti locus alleles.

Alleles↗

The behavior of skin grafts incompatible with respect to skin alloantigens on mice rendered tolerant at birth with lymphoid cells.

It has been reported that lethally irradiated adult B6 mice restored with (A X B6) hemopoietic cells subsequently reject adult A-strain skin grafts because they are not tolerant of A-strain skin-specific (Sk) antigens. This thesis has been confirmed by a series of experiments conducted on neonatally treated animals. Thus sublethally irradiated neonatal B6 mice, inoculated with (A X B6) lymphoid cells, permanently accept these cells while subsequently rejecting adult strain A skin grafts. Further evidence that the destruction of these grafts results from the reaction of the host to Sk antigens, is provided by the fact that similarly treated recipients often permanently accept neonatal A-strain skin. Such grafts usually induce tolerance of adult A-strain skin grafts.

Age Factors↗

The development of regional pigmentation patterns in black and tan (at) mice.

Mice which express the black and tan (at)allele at the agouti locus have black dorsal and yellow ventral hairs. To determine the site of action of this allele, the kind of hair pigment produced by various dermal-epidermal recombinations of dorsal and ventral black and tan (at/at), ventral nonagouti (a/a) and ventral yellow (Ay/a) embryonic skin has been investigated. The results indicate that it is the dermis which is responsible for the development of regional pigmentation patterns in black and tan mice.

Alleles↗

The influence of foster nursing on the survival and immunologic competence of mice and rats.

A series of experiments were undertaken in mice and rats to confirm the report that foster nursing rats of one strain, on mothers of a different strain, can influence their survival and immunologic competence as a consequence of their receiving a significant number of immunologically competent leukocytes via the milk. These experiments have included foster nursing mice and rats, either immediately after birth, or when 25 to 36 hr old, on H-2 incompatible and Ag-B compatible and incompatible mothers, respectively, and challenging them with ear skin grafts of the same genotype as their surrogate mother. They also have included fostering animals rendered tolerant of their surrogate mother's transplantation antigens. In no instance was any evidence obtained that foster nursing can prejudice the survival or influence the immunologic competence of mice or rats.

Animals↗