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Biomedical subjects

J F Douglas

Publications and source records attributed to J F Douglas.

At least 55 records · Page 3Linked to original sources

Natural killer cells in viral arthritis.

Changes in natural killer (NK) cell activity were studied in patients with polyarthritis associated with rubella or Ross River virus infections. In 30 of 32 Ross River virus patients, peripheral NK cell activity was depressed at some stage of the disease but returned to normal levels as patients recovered from arthritic symptoms. Similar changes did not occur in rubella patients and no difference was found between changes in peripheral NK activity and serum interferon (IFN) levels in rubella patients with arthritis and those without. Neither the peak of NK cell activity in peripheral blood lymphocytes (PBL) recovered early in Ross River virus and rubella infections, nor the depression of NK cell activity late in Ross River virus infections could be correlated with changes in serum IFN levels. The decrease in PBL-NK cell activity in epidemic polyarthritis (EPA) patients could not be attributed solely to loss of NK cells from the peripheral circulation because limiting-cell-dilution (LCD) analyses indicated changes in peripheral NK cell activity were due to changes in both the number and lytic activity of NK cells. Despite the association between HLA-DR7 and EPA no differences were found in levels of peripheral NK cell activity in DR7+ and DR7- EPA patients. The demonstration that peripheral NK cells could kill autologous synovial cells suggested that NK cells in joints of EPA patients may contribute to the arthritis associated with Ross River virus infection.

Adult↗

The influence of HLA-A, B, and DR matching on graft survival in primary cadaveric renal transplantation in Belfast.

HLA-DR matching has been shown in a retrospective study of 72 renal transplant patients to significantly enhance graft survival at 12 months. HLA-A and -B antigen matching also increased the graft survival rate significantly. Analysis of combined HLA-A, -B and -DR matching suggested an improvement in graft survival rate with better matching, but this did not attain statistical significance. It is now our policy to use HLA-DR matching prospectively and to ensure that all recipients receive a kidney with a maximum of 1 HLA-DR incompatibility and a minimum of 2 HLA-A and -B antigens shared.

Graft Survival↗

Mismatching for HLA-A, -B antigens and renal graft survival.

One hundred and seventy five recipients of a kidney graft were analyzed to see if mismatching for certain HLA-A, -B antigens was detrimental to graft survival. No association was found between graft survival and a specific mismatched HLA-A, -B antigen.

Blood Grouping and Crossmatching↗

Two-year inhalation toxicity study of propylene in F344/N rats and B6C3F1 mice.

Chronic toxicity studies of propylene were conducted by exposing groups of 50 F344/N rats and 50 B6C3F1 mice of each sex in chambers to air containing the chemical in concentrations of 5000 and 10,000 ppm, 6 hr per day, 5 days per week, for 103 weeks. Groups of 50 rats and 50 mice of each sex in similar chambers received clean air only on the same schedule and served as controls. Survival and mean body weights of exposed and control male and female rats and mice were similar. In exposed rats, increased incidences of nonneoplastic lesions were observed in the nasal cavity. These consisted of epithelial hyperplasia in female rats exposed to the high concentration, and squamous metaplasia in female rats exposed to both concentrations and in male rats exposed to the low concentration. In addition, inflammatory changes characterized by an influx of lymphocytes, macrophages, and granulocytes into the submucosa and by granulocytes into the lumen occurred in male rats of both exposure groups. There was no evidence of nasal cavity lesions in exposed mice, suggesting a species difference in sensory irritation to propylene. There were no treatment-related increases or decreases in tumor incidence in the exposed groups relative to controls for either rats or mice. These data suggest that inhaled propylene induces signs of nasal cavity toxicity in rats but not in mice, and that the chemical is not carcinogenic to either species at the concentrations tested.

Alkenes↗

No evidence of carcinogenicity for L-ascorbic acid (vitamin C) in rodents.

Carcinogenesis studies of L-ascorbic acid were conducted by offering diets containing 0, 25,000 or 50,000 ppm L-ascorbic acid to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex for 103 wk. Survival of dosed and control female rats and of dosed and control female mice were comparable. Survival of high-dose male rats was slightly greater than that of the controls, whereas survival of high-dose male mice was significantly greater than that of the controls. There was no observed differences in neoplasms between treated and control groups that were considered related to L-ascorbic acid. In female rats, several lesions usually seen in aged animals showed a dose-related decline. Under the conditions of these studies, L-ascorbic acid given at 2.5% or 5.0% in the diet for 103 wk was not toxic or carcinogenic for male and female F344/N rats or for male and female B6C3F1 mice.

Animals↗

Pre-transplantation immunological monitoring and graft survival in recipients of renal allografts.

Various immunological parameters were measured pre-transplantation in 82 renal transplant recipients. The results were compared with the clinical course of the recipient post-transplantation and with the results of 40 controls. Only one test C3 inactivation products (C3i) was associated with transplant outcome in that 0/30 patients with no rejection episodes had C3i whereas 9/38 patients with rejection episodes, including 3/12 patients whose graft failed, had C3i.

Adult↗

Plasma prednisolone concentrations and kinetics in renal transplant patients.

Plasma prednisolone concentrations were measured in 26 renal transplant (RT) patients and five control subjects. A linear relationship was found between prednisolone dosage in mg/kg and area under the plasma concentration time curve in seven stable RT patients (r = 0.98) and in all subjects (n = 19) with estimated prednisolone clearance rates (CLp) between 0.075 and 0.11 L/kg/hr (r = 0.96). The greatest deviation from this occurred in five patients having reduced CLp with prolonged prednisolone half life (t1/2p) and in one having increased CLp while taking phenytoin. Three of the five with reduced clearance had steroid induced diabetes and one a Cushingoid appearance. There was some correlation between peak plasma prednisolone and dosage (r = 0.77) in all subjects, but none between creatinine clearance and t1/2p or CLp.

Dose-Response Relationship, Drug↗

Carcinogenicity testing of phthalate esters and related compounds by the National Toxicology Program and the National Cancer Institute.

Five phthalate ester and related compounds (phthalic anhydride, phthalamide, di(2-ethylhexyl) phthalate, di(2-ethylhexyl) adipate and butyl benzyl phthalate) have been tested for carcinogenic effects in standard lifetime rodent feeding studies. Groups of 50 male and female rats and mice were fed diets containing various concentrations of the test chemicals for 102-106 consecutive weeks. The dietary concentrations were estimated to be maximally tolerated doses and half maximally tolerated doses. All animals that died during the study and all survivors at the end of two years were examined grossly and microscopically for the presence of tumors. The incidences of animals with tumors at a specific anatomic site in the treated groups and the controls were compared statistically. Neither phthalamide nor phthalic anhydride increased tumor incidences in rats or mice. Di(2-ethylhexyl) phthalate increased the incidences of liver tumors in rats and mice of both sexes, while di(2-ethylhexyl) adipate caused liver tumors in male and female mice, only. Butyl benzyl phthalate did not cause tumors in male or female mice, but the incidence of myelomonocytic leukemia in butyl benzyl phthalate-treated female rats was significantly greater than that in the controls. Chemically induced early deaths in the butyl benzyl phthalate-treated male rats precluded an evaluation of carcinogenic potential in this sex. Under the conditions of these tests, di(2-ethylhexyl) adipate was considered to be carcinogenic in both rats and mice and di(2-ethylhexyl) adipate was considered to be carcinogenic in mice. The evidence for carcinogenic effects of butyl benzyl phthalate in female rats was judged to be equivocal because of the variable nature of the incidence of myelomonocytic leukemia in Fischer 344 rats. Phthalamide and phthalic anhydride did not exhibit carcinogenic effects in these studies.

Animals↗

Increased incidence of IgM class smooth muscle antibody in patients after renal transplantation.

Autoantibodies were examined in 70 patients with renal failure, before acceptance on a hemodialysis program, during the program, and up to 3 months after renal transplantation. Smooth muscle antibody (SMA) in the IgM class was detected in 76% of the patients after transplantation compared with 14% before transplantation. This increase was significant at the 5% level. Furthermore, two groups of patients were distinguished on the basis of a 4-fold or greater increase or no demonstrable increase in the titer of IgM SMA after transplantation. Rejection episodes occurred more frequently amongst patients from this former group (67%) compared with the latter group (35%).

Adult↗

Advantages of low dose steroid from the day after renal transplantation.

We have used a low dose of steroid (20 mg of prednisolone), commencing the day after transplantation, for 151 consecutive renal transplants in 141 patients. Five patients received grafts from living related donors, 146 received cadaver grafts. All patients received azathioprine for routine immunosuppression and the first 47 received a single dose of actinomycin C i.v. for treatment of rejection. No other immunosuppressive drugs were used. This treatment provided satisfactory immunosuppression as 109 of 151 grafts continue to function for periods of 3 months to 10 years and, of 42 grafts lost, only 17 failed from rejection. The cumulative survival of first cadaver grafts at 1 and 2 years in recipients of all ages (7 to 55 years) was 77.9 and 76.0%, respectively; in recipients 15 to 34 years old, 90.9 and 86.1%, respectively. Twenty-three patients died, no patient died from infection during the admission for transplantation, and infection played a part in the deaths of only four patients. The incidence of other complications was low; seven patients developed gastrointestinal complications, one died, four patients developed diabetes, all survived; only one patient developed avascular necrosis of bone.

Administration, Oral↗

Bilateral slipping of the upper femoral epiphysis in end-stage renal failure. A report of two cases.

Two cases of bilateral slipping of the upper femoral epiphysis in boys with end-stage renal failure due to megacystis and mega-ureter with severe renal osteodystrophy are reported. In one patient the lesion emerged after a dystonic reaction to drugs and in the other after bilateral nephro-ureterectomy. Neither showed marked elevation of growth hormone levels, but both had evidence of renal rickets with severe secondary hyperparathyroidism. Both had a satisfactory response to bilateral internal fixation. The complication should be borne in mind in all young patients with renal osteodystrophy.

Adolescent↗

Urological complications in 119 consecutive renal transplants.

One hundred and nine patients undergoing 119 transplants have been followed up from 8 months to 9 years. Urological complications occurred in 16 transplants, an incidence of 13.4%. Ureteroneocystostomy was performed primarily in all cases; in 98 by the conventional Politano-Leadbetter technique with 9 (9.2%) urological complications and in 32 by an extravesical technique with 7 (21.8%) urological complications. One patient died as a result of ureteric obstruction, without operation. In 3 patients with lower ureteric obstruction, transurethral ureteric meatotomy was successful in 2 cases and resulted in no change in renal function in the third. Two patients with urinary fistulae were managed successfully by continuous drainage with indwelling urethral catheters. The remaining 10 patients required 12 open surgical procedures for relief of ureteric obstruction, with improvement in function in 7 patients.

Follow-Up Studies↗

Evaluation of procedures suggested for reducing the pathology workload in a carcinogenesis testing program.

A sampling procedure for reducing the pathology workload in evaluating a carcinogenicity bioassay was utilized for a rodent bioassay. The use of the procedure resulted in 50 percent fewer tissues being examined histologically, in the control groups and 12 percent fewer tissues in the treatment groups. The obvious saving in pathologist's time was negated by an increase in technician time, interference with quality control procedures and loss of nontumor pathology information.

Animals↗

Low dose steroid from the day following renal transplantation.

Azathioprine combined with a low dose of steroid (20mg of prednisolone) commencing the day following transplantation has been used for immunosuppression for 151 consecutive renal transplants in 141 patients (146 cadaver grafts, 5 living related donor grafts). Immunosuppression was satisfactory as 109 grafts function from 6 months to 10 years, 17 of 42 grafts lost failed from rejection. No patient died from infection before 90 days, 4 died later from infection, 2 associated with anti-rejection therapy. Seven patients developed gastrointestinal complications, 1 died; 4 developed diabetes, all survived; only 1 patient developed avascular necrosis of bone.

Adolescent↗