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Biomedical subjects

A S MacDonald

Publications and source records attributed to A S MacDonald.

At least 55 records · Page 3Linked to original sources
PubMed1993

Structural changes in the subcutaneous compartment in morbid obesity.

Most of the excess fat that accumulates in the morbidly obese is accommodated in the subcutaneous compartment (SCC), specifically in the adipose tissue lobules of the panniculus adiposus which enlarge and expand the SCC. However, the fibroelastic septa that are attached to the skin on one side of the SCC and to the deep fascia on the other invest each lobule and thereby offer resistance to the enlarging lobules. We report observations made during pathologic examinations of the abdominal wall SCC that were surgically excised by abdominal dermo-panniculectomy from 48 morbidly obese subjects after gastroplasty and weight loss. Lobules were large but varied notably upwards in size and, to some extent, shape. Simultaneously upon incision of the SCC, the lobules bulged above and the septa retracted below the same cut surfaces. Light microscopy revealed disruptions of septal elastic fibers, calcification of septa and septal arteries and necrosis of adipocytes, all sparsely distributed. Certain questions and facts emerge from these observations. Are the variations in lobule sizes normal, or do they reflect uneven fat deposition or mobilization during weight gain or loss respectively? Is there any correlation between lobule and adipocyte sizes? The tightly coupled phenomena of lobule-bulging and septal-retraction indicate that the lobules and septa are subjected to compressional and tensile stresses respectively in the intact, non-incised SCC. The histologic changes might be consequences of these stresses. Studies of the variations in body fat distribution and in adipocyte size have contributed to an understanding of obesity pathogenesis. The relevance of the present findings is unknown at this time, but these appear to have potential implications for studies of the morphogenesis of obesity. Confirmation of these findings, particularly the lobule variations, is required so that these can be compared with those in never-obese subjects and in morbidly obese subjects without prior weight loss.

Abdomen↗
PubMed1993

Early prediction of renal allograft loss beyond one year.

Despite significant improvements in the results of renal transplantation since the introduction of cyclosporin, graft loss beyond the 1st year remains a significant and unresolved problem. In a retrospective analysis, 348 cyclosporin-treated renal transplant recipients with a functioning graft at 12 months were studied. Forty-eight patients in whom graft failure occurred in the 2nd and 3rd years were compared to 300 patients who maintained graft function beyond this time. Both groups were comparable with respect to donor and recipient features. Factors reflecting recipient immunological responsiveness--sensitization, previous transplantation and early rejection episodes--continued to affect graft survival beyond the 1st year. Surprisingly, there was a higher incidence of prior transfusion in the group with graft failure in the 2nd and 3rd years than in those with longer function (65% vs 24%). Serum creatinine levels at 3 and 6 months were also predictive of graft loss amongst patients with a functional graft at 1 year. It remains to be answered whether new immunosuppressive drugs and strategies will overcome these risks for late graft loss.

Adult↗
PubMed1993

Reduction by combination prophylactic therapy with CMV hyperimmune globulin and acyclovir of the risk of primary CMV disease in renal transplant recipients.

CMV-seronegative recipients of kidneys from CMV-seropositive donors (D+/R+) are at highest risk for developing clinical CMV disease. Even with routine prophylactic use of low-dose acyclovir we had a CMV disease incidence of 26% (5/19) in these patients. Published studies using either acyclovir or CMV hyperimmune globulin (HIG) alone as prophylaxis have also shown clinical disease in 20-30% of D+/R+ patients--less than controls but still significantly greater than in comparable CMV+ recipients (R+). The purpose of this study was to determine whether the risk of primary CMV disease in D+/R- patients was reduced by prophylaxis with combined CMV-HIG and low-dose acyclovir as follows: CMV-HIG (Immuno) 1 ml/kg i.v. immediately prior to transplantation and at 3-week intervals for 6 months; acyclovir 600 mg/day p.o. for 3 months. A total of 361 consecutive renal transplants were studied prospectively. All D+/R- pts (n = 73) received CMV-HIG and acyclovir, the others (91 D+/R+, 74 D-/R+, 123 D-/R-) received only low-dose acyclovir. The incidence of clinical CMV disease, CMV-related graft loss, graft and patient survival, and the influence of ALG and OKT-3 were analyzed and compared between groups. Of the 361 patients only 18 (5%) developed CMV disease, with 5 CMV-related graft losses. CMV disease occurred in only 10% of the D+/R- patients, lower than in previously reported studies. Significantly the incidence was as low as in CMV+ recipients of kidneys from both CMV+ (6%) and CMV- (7%) donors. Use of OKT-3 for steroid-resistant rejection increased the risk of developing CMV disease: 11/50 (22%) receiving OKT-3 developed CMV disease vs. only 7/311 (2%) who did not (P < 0.001); 11/18 (61%) with CMV disease had received OKT-3. ALG induction immunosuppression did not increase the risk of CMV in patients who subsequently received OKT-3. No patient developed CMV disease after discontinuing prophylaxis. There were no complications related to either CMV-HIG or acyclovir use. Compared with all other patients, the D+/R- group had superior graft survival at 1 and 3 years (94% vs. 87% and 86% vs. 74%, P < 0.05) but similar patient survival. Combined CMV-HIG and low-dose acyclovir appear to be better than either agent alone in preventing primary CMV disease in CMV- patients who receive CMV+ kidneys. Low-dose oral acyclovir (600 mg/day) may be as effective in preventing CMV disease as higher-dose prophylactic regimens, at least when accompanied by CMV-HIG.(ABSTRACT TRUNCATED AT 400 WORDS)

Acyclovir↗
PubMed1992

The incidence and impact of early rejection episodes on graft outcome in recipients of first cadaver kidney transplants.

The objective of this study was to define the incidence and significance of acute rejection occurring in the first year following transplantation. The influence of contemporary induction immunosuppression on rejection, as well as the effect of rejection on graft and patient loss, renal function, and maintenance immunosuppression during the first year in 110 recipients of first cadaver renal transplants were analyzed. All patients received CsA, Aza, and prednisone for 30 days with withdrawal of Aza at 30 days and then prednisone at 105 days; 57 patients were prospectively randomized to receive ALG (Merieux) until serum creatinine was less than 300 mumol/L. Short-term ALG administration did not influence the incidence, severity, nature, or outcome of rejection episodes. Fifty-five (50%) patients had at least 1 rejection in the first 90 days. All patients with delayed graft function and 7/8 (88%) sensitized patients (current PRA greater than 50%) had at least 1 rejection episode; 71% (n = 35) of all rejection episodes occurred in the first 30 days posttransplant. Patients rejection free at 90 days remained rejection free the entire first year. Graft loss was 18% for rejections in the first month, 13% for rejections occurring later (P = NS); 20% (n = 11) of patients had a second rejection and 1% (n = 2) had a third rejection. The risk of graft loss was 9% with a first rejection, 38% with a second rejection, and 50% with a third rejection. Of 12 (22%) rejections that were steroid resistant, 10 (83%) were reversed with OKT3. One-year graft survival for patients without rejection, with steroid-sensitive rejection, and with steroid-resistant rejection was 96%, 88% (P = ns), and 58% (P less than 0.001), respectively; 1 year SCr was 168 +/- 93, 196 +/- 77 (P = ns), and 268 +/- 96 microMol/L (P less than 0.05), respectively. Patients free of rejection and with stable renal function continued to do well on maintenance CsA monotherapy, and they were more likely to be on CsA monotherapy than those with rejection episodes (P less than 0.01).

Adult↗
PubMed1991

Final report on a placebo-controlled, double-blind, randomized, multicentre trial of cyclosporin treatment in active chronic Crohn's disease.

In a previous report we published the immediate results of a 3-month placebo-controlled trial (n = 34) showing that cyclosporin (n = 37) has a beneficial therapeutic effect in active chronic Crohn's disease. Here we report on the final outcome of the patients. During the 3-month tapering-off period eight initially improved patients (36%) in the cyclosporin group worsened, as did six (55%) in the placebo group. The therapeutic gain of cyclosporin treatment was consistently significant during this period. It ranged from 22% to 25% (95% confidence limits, 2-46%). An outcome ranking showed that 7 patients of the cyclosporin group (19%) were substantially improved, 7 (19%) moderately improved, and 23 (62%) not improved after the tapering off. In contrast, no significant differences were seen during the 6-month follow-up period. Four patients of the cyclosporin group (11%) were substantially improved, 3 (8%) moderately improved, and 30 (81%) not improved at final follow-up. Significant interactions between cyclosporin and prednisolone treatment were demonstrated both at the end of the initial treatment period and at the end of the tapering-off period. We conclude that a short course of cyclosporin treatment does not result in long-term improvement in active chronic Crohn's disease.

Chi-Square Distribution↗
PubMed1991

Sequential discontinuation of azathioprine and prednisone in renal transplantation.

We report the time course of rejections in 110 patients of first cadaver kidney grafts entered into a randomized controlled trial of induction ALG vs continuous IV CyA, with both groups receiving Aza for 30 days and Pred for 3 months. There was no difference in 1-year graft or patient survival in the two induction regimens. Despite a slight delay in time to first rejection, the number, severity, and outcome of rejections were the same in both. Fifty percent of patients never had a rejection, and 80% of these were on CyA monotherapy at 1 year vs only 22% in patients with rejections. Thirty-five percent had a rejection in the first month, and one fourth of these had a repeat in the second month. The risk of graft loss was 10% with a first, 38% with a second, and 50% with a third rejection. First rejections occurring after 30 days rarely caused graft loss and rejection after 90 days proved to be unusual.

Administration, Oral↗
PubMed1989

A placebo-controlled, double-blind, randomized trial of cyclosporine therapy in active chronic Crohn's disease.

We randomly assigned 71 patients with active chronic Crohn's disease who were resistant to or intolerant of corticosteroids to treatment with oral cyclosporine (5 to 7.5 mg per kilogram of body weight per day) or placebo for three months. Disease activity was assessed on a clinical grading scale without knowledge of the treatment given. At the end of the treatment period, 22 of the 37 cyclosporine-treated patients (59 percent) had improvement, as compared with 11 of the 34 placebo-treated patients (32 percent) (P = 0.032). During cyclosporine treatment, there was significant improvement in plasma orosomucoid levels (P = 0.0025) and the Crohn's Disease Activity Index (P = 0.00012). The effect of treatment became evident after two weeks. In the subsequent three months, during which the patients were gradually withdrawn from treatment, the improvement continued in 14 of the 37 patients (38 percent) in the cyclosporine group and in 5 of the 34 (15 percent) in the placebo group (P = 0.034). No serious adverse events were observed. We conclude that cyclosporine has a beneficial therapeutic effect in patients with active chronic Crohn's disease and resistance to or intolerance of corticosteroids.

Administration, Oral↗
PubMed1989

Cyclosporine as primary therapy for A-matched living related donor kidney graft recipients.

Between 1981-87, 48 HLA identical sibling graft recipients were allocated to one of three treatment groups: Group I-15 patients Aza and Pred; Group II-12 CyA alone; Group III-21 CyA and steroids. Only one patient died from a fatal hereditary disease. Graft survival was 100% at one year in all groups and at three years was 86% for Aza, 94% for CyA alone and 100% for CyA and steroids. Rejection episodes occurred in 50% of Aza patients versus 18% in the CyA groups. However 55% of CyA patients require anti-hypertensives versus 20% of Aza recipients, and 12% of CyA patients were switched because of drug toxicity. In a previous study of 36 Aza treated A-matched patients, five of eight losses occurred after the first 5 years--most related to long term effects of immunosuppression. We may have to wait for longer follow-up before drawing conclusions regarding the use of CyA in identically matched living related recipients.

ABO Blood-Group System↗
PubMed1989

ABO-incompatible living related donor kidney transplantation: report of two cases.

The courses of two recipients of ABO-incompatible HLA-identical living related donor kidney transplants are described, the first an A into O and the second a B into A. Both patients were prepared by a month of preoperative azathioprine and a week of plasmapheresis to reduce isohemagglutinin titers in one to 1:2 and in the other to 0 at the time of transplant. Both had early mild steroid-reversible rejections, and the first patient has had an uneventful subsequent course 20 months postgrafting on low-dose cyclosporine and prednisone. The second patient developed a further immunologic event at 1 month that may have been isohemagglutinin mediated or may have been rejection but subsided with OKT3 therapy and plasmapheresis. She lost her graft at 5 months despite normal function during attempts to repair a ureteric fibrosis. Neither patient had donor-specific transfusion or splenectomy. This approach is feasible and should be considered for those patients having related but ABO-incompatible donors.

ABO Blood-Group System↗
PubMed1989

Living related donor kidney grafts in the cyclosporine era.

The results of 120 LRD kidney grafts, 49 HLA identical and 71 haploidentical, performed between 1981 and 1987 during the CyA era have been analyzed. The reduction in the incidence of rejection in diploidenticals with CyA vs AZA did not increase short- or long-term graft survival but was accompanied by worse kidney function and a greater need for antihypertensives. CyA did improve the results in haploidentical recipients over our historical experience, although prior sensitization was still a major hazard in this group.

Adolescent↗
PubMed1988

The effect of dose of thoracic irradiation on recurrence in patients with limited stage small cell lung cancer. Initial results of a Canadian Multicenter Randomized Trial.

Patients with limited stage small cell lung cancer were initially randomized to receive either three courses of Cyclophosphamide, Adriamycin, and Vincristine (CAV) followed by three courses of VP-16 and Cis-platin (VP-PT) or six courses of alternating CAV and VP-PT. Responding patients received prophylactic cranial radiation (PCI) after three courses of chemotherapy (CT) and loco-regional thoracic radiation (LRTR) after six courses. No maintenance chemotherapy was given. Patients receiving LRTR were randomized to receive either 25 Gy in ten fractions over 2 weeks (SD) or 37.5 Gy in 15 fractions over 3 weeks (HD). In both arms the pre-chemotherapy disease was treated with a 2 cm margin around the primary tumor volume. The mediastinum was included in the treatment volume and the supraclavicular nodes were also included if involved originally. The spinal cord was shielded after 32 Gy. Of the 333 patients enrolled by the time the trial closed in October 1984, 168 were eventually randomized to LRTR and are eligible for response assessment. The overall response rate after combined RT and CT was 94% (CR 67%, PR 27%). The CR rate for SD was 65% and for HD 69%. The combined treatment was well tolerated by most patients. Forty-nine percent of HD patients developed dysphagia compared to 26% of those SD (p less than 0.01). At the time of this analysis the median duration of follow-up since randomization to radiotherapy is 30 months. The median local progression-free survival on HD is 49 weeks. On SD it is 38 weeks (p = 0.05, one sided). The actuarial incidence of local progression by 2 years is 69% on HD and 80% on LD. There is as yet no significant difference in overall survival between the two arms. It appears that HD radiotherapy as administered in this study may have an impact on local control, but it is too early to determine if this will translate into a survival benefit.

Adult↗