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Biomedical subjects

A S MacDonald

Publications and source records attributed to A S MacDonald.

At least 73 records · Page 4Linked to original sources

Long-term follow-up of cyclosporine-treated renal allograft recipients.

Results in 355 Cs-treated renal graft recipients have been analyzed. The majority of graft losses occurred early. Prior sensitization and repeat grafts were clear-cut early risks for cadaver recipients but not live-related donor grafts. In neither group was presensitization clearly a risk factor for late losses, although repeat grafts were much more at risk late. The majority of late losses was due not to chronic rejection but to deaths from cardiovascular disease and cancer, and a surprisingly high number from noncompliance.

Actuarial Analysis↗

Repeat cadaver kidney transplantation using cyclosporine A immunosuppression.

Repeat cadaver kidney transplantation using azathioprine immunosuppression carried a higher risk of graft loss than primary transplants. We analyzed the results of repeat cadaver kidney grafting with cyclosporine A immunosuppression. A total of 33 cyclosporine A-treated patients received the second kidney transplant at varying intervals after failure of the first transplant. Graft survival at 1 year was 66 per cent. A concurrent group of 189 cyclosporine A-treated first cadaver kidney recipients had a 1-year graft survival rate of 75 per cent, although this better result was not statistically significant (p greater than or equal to 0.25). A historical group of 31 azathioprine-treated second graft recipients had a significantly worse 1-year graft survival rate of 45 per cent compared to the cyclosporine A second graft group (p less than 0.1). Patient age, sex, early first graft loss, interval between transplants and the presence of panel reactive antibodies were not factors in predicting second graft outcome. A complete DR mismatch appeared to worsen the second transplant survival. These findings indicate that early graft survival of cyclosporine A-treated repeat cadaveric transplants is acceptable and is better than azathioprine-treated first or second grafts.

Actuarial Analysis↗

Canadian multicenter randomized trial comparing sequential and alternating administration of two non-cross-resistant chemotherapy combinations in patients with limited small-cell carcinoma of the lung.

In order to assess the effect of scheduling of chemotherapy on the outcome of patients with limited small-cell lung cancer (SCLC), the Clinical Trials Group of the National Cancer Institute of Canada carried out a randomized trial comparing the alternation of cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, OH; doxorubicin) and vincristine (CAV) with etoposide (VP-16) and cisplatin for six cycles to the administration of these two combinations in a sequential fashion (three cycles of CAV followed by three of VP-16/cisplatin). Three hundred eligible patients were enrolled on the trial from September 1981 to October 1984. All responding patients were also treated after completion of chemotherapy with thoracic irradiation in randomly allocated doses of 2,000 and 3,750 cGy. The complete response (CR) rate to chemotherapy was slightly, but not significantly, higher on the alternating arm (52% v 44%, P = .20). However, there was no difference in disease-free or overall survival on the alternating and sequential arms, respectively (47.3 weeks v 45.1 weeks, P = .26; 61.7 weeks v 59.5 weeks, P = .56). Data on the effect of radiotherapy dose on survival are not yet mature, but it does not appear the results of this portion of the trial will alter the interpretation of the chemotherapy comparison. Patient characteristics favorably influencing survival were female sex, good performance status, younger age, and absence of supraclavicular node involvement. Two interpretations of these and other results in SCLC are suggested: (1) the difference between the schedules used is too small for the predictions of the Goldie-Coldman model to be realized in a trial of this size, or (2) VP-16/cisplatin is actually a superior regimen and any schedule that exposes patients to these drugs early in treatment will produce improved results.

Adult↗

A randomized study of cyclosporine with and without prednisone in renal allograft recipients. Canadian Transplant Group.

Sixty-nine patients receiving Cs after cadaveric or LRD renal transplants were randomly allocated to receive prednisone or no prednisone beginning on the day of transplant. There were 36 in the prednisone group and 33 in the group assigned to no prednisone. Of these latter, only seven (21%) never received prednisone and an additional four had one short course for rejection episodes (11%). Of the remaining 22 who were placed on continuous steroids, only 12 met rejection criteria and either some or all of the remainder probably had Cs nephrotoxicity. The patient and graft survival were better but not statistically so in the no-prednisone group (97% v 89%) and (88% v 78%), and the number of infections was only half that of the prednisone-treated group (22% v 42%). A policy of withholding steroids except for rejection episodes does not prejudice graft or patient survival in Cs-treated patients.

Cyclosporins↗

Conversion from cyclosporine to azathioprine in renal graft recipients.

Only one of six patients in whom a clinical diagnosis of rejection was confirmed by both biopsy and FNA benefited from a switch from cyclosporine to azathioprine. Nine patients, in whom nephrotoxicity and rejection could not be separated and in whom the biopsy was positive but the FNA negative, improved when converted to cyclosporine. This improvement was, however, followed by subsequent rejection episodes in four of these patients. This study suggests caution in changing from CsA therapy in patients with unstable function.

Azathioprine↗

Pneumonia in renal transplant patients.

Between January 1976 and March 1982, 28 episodes of pneumonia occurred in 26 renal transplant patients. The overall mortality rate was 46%. Of the 16 patients with nosocomial pneumonia 9 (56%) died, whereas of the 12 patients with community-acquired pneumonia 4 (33%) died. In all 9 cases of unknown cause the response to empiric treatment was prompt, whereas in 4 of the 10 cases of monomicrobial pneumonia and 8 of the 9 cases of polymicrobial pneumonia the patient died. Cytomegalovirus was the sole cause of the pneumonia in two patients and a contributing cause, along with aerobic gram-negative bacteria, in another five, four of whom also had a fungal infection. Two patients, both of whom survived, had nosocomial Legionnaires' disease.

Adult↗

Antithymocyte globulin in cadaver renal grafts: prophylaxis and antirejection therapy with three different preparations.

Three different preparations of antithymocyte globulin were used to treat recipients of cadaver kidney transplants. Twenty patients received Connaught Institute/Armand-Frappier ATG prophylactically beginning on the day of grafting and achieved superior graft and patient survival compared to 18 concurrent controls. Pressimmune as a 5-day course was able to reverse steroid resistant rejections in 20 of 31 recipients as was ATGAM in three of six treated patients receiving it for 10 days. These short courses were associated with a 16% early and a 10% late relapse rate. The combination of high steroid therapy, maintenance azathioprine and ATG was associated with an infection rate of 22%.

Antilymphocyte Serum↗

Pancreatic autotransplantation: duct drainage to bladder, duodenum, stomach, compared to duct ligation or free drainage into the peritoneal cavity.

The pancreas of the dog was divided into segments of left lobe (tail), body and uncinate, but with in-situ blood supply to each segment intact, and comparisons within the same dog were made of various techniques of handling the pancreatic duct. Ligating the duct or allowing it to drain freely into the peritoneal cavity were both associated with high morbidity and severe pancreatitis and fibrosis with exocrine and ultimately, endocrine atrophy. Duct drainage by a duct to mucosal anastomotic technique, whether to stomach, small bowel or urinary bladder, prevents pancreatitis and preserves normal exocrine and endocrine function. A facile technique of pancreatic duct to urinary bladder anastomosis using the uncinate process is described and the lack of deleterious effect of pancreatic exocrine secretions on the uroepithelium is confirmed.

Animals↗

Radionuclide imaging of metastases from renal-cell carcinoma by 131I-labeled antitumor antibody.

On immunofluorescence assay, goat antisera reacted with renal-cell carcinomas from 20 patients, but not with adult normal human tissues (including patient's normal kidney). After in travenous injection, the 131I-labeled antibody localized preferentially in metastatic renal carcinoma in 6 consecutive patients. Labeled antitumor antibodies may have the specificity for tumor imagining which current radiopharmaceuticals lack.

Adenocarcinoma↗

Symposium on intensive care: 3. Upper gastrointestinal bleeding in the intensive care unit.

Bleeding from hemorrhagic erosions in the stomach or duodenum of seriously ill patients is associated with a high mortality. While the pathogenesis of such lesions is by no means certain, it is known that they are universal after shock, sepsis or severe burns. Fiberoptic endoscopy has become the most valuable means of diagnosis. This should be preceded by gastric irrigaiton, which usually sufficies to control bleeding caused by acetylsalicylic acid or alcohol, or both. Neutralization of gastric acidity is essential. The histamine HI-receptor antagonist, cimetidine, was used in 27 patients with erosive gastritis, and bleeding ceased in 24. There is a prospect that sugh agents will obviate the necessity of total gastrectomy in the occasional resistant cases in favour of conservative surgery.

Antacids↗

A comparative study of peripherally inserted silicone catheters for parenteral nutrition.

One hundred patients receiving parenteral nutrition with lipids and hypertonic amino acids and glucose were divided into five groups of 20, depending on the type of intravenous catheter used for the infusion. Least satisfactory were the short Butterfly needles (average 3.3 days in place) and the long peripherally inserted polyvinyl central venous catheters (average 6.2 days in place). Subclavian catheters of polyvinyl (average 15.3 days) or silicone elastomer (average 17.5 days) were equally efficacious. A new long silicone elastomer catheter inserted peripherally was most satisfactory (average 29.5 days). Problems common with polyvinyl catheters (phlebitis, thrombosis, and sepsis) rarely occurred with either the long or short silicone elastomer catheter.

Catheterization↗

Immunochemotherapy of malignant melanoma with chlorambucil-bound antimelanoma globulins: preliminary results in patients with disseminated disease.

Thirteen consecutive patients with inoperable recurrent malignant melanoma were treated by immunochemotherapy with the use of chlorambucil noncovalently bound to goat or rabbit antihuman melanoma globulins. The next consecutive 11 patients fulfilling the criteria for admission into this study were treated with chemotherapy only, i.e., dimethyltriazenoimidazole carboxamide (DTIC). Follow-up was for a minimum of 29 months or until death. Two patients showing an objective response to immunochemotherapy had disease confined to lymph nodes and cutaneous sites; 5 others showed stabilization of cutaneous, nodal, and visceral disease, and 6 patients showed progression of their disease. The median survival of the responders and stabilizers was 20 months, but only 3.5 months for patients with disease progression. None of the 11 patients treated with DTIC had objective tumor regression, and all died within 11 months of the start of treatment with a median survival of 3 months. Immunochemotherapy significantly prolonged the survival compared to that in the DTIC-treated group (P less than 0.05). No hematologic or renal toxicity was detected after immunochemotherapy, but 2 patients in this group developed anaphylactic reactions. Skin reactivity tests to dinitrochlorobenzene and purified protein derivative were of no prognostic value

Adolescent↗

Treatment of stress-induced upper gastrointestinal/hemorrhage with metiamide.

The H-2-blocking antihistamine metiamide was used to treat 14 episodes of bleeding from the stomach or duodenum in eleven patients. In 11 instances bleeding was due to erosive gastritis or duodenitis and bleeding promptly ceased after one or two doses of 300 mg at 6 h intervals and did not recur as long as the drug was continued. In the 2 instances in which bleeding continued, chronic ulcers had eroded into major blood-vessels. There were no complications from the drug even in five patients with severe bone-marrow suppression after renal transplantation. Metiamide seems to be a safe and highly effective agent in the control of bleeding due to erosive gastritis.

Adolescent↗