Biomedical subjects
D Kahn
Publications and source records attributed to D Kahn.
New rapid technique for renal transplantation in the rat.
Present techniques for renal transplantation in the rat include a period of 20-25 minutes warm ischemia. Our method combines a recently described sleeve anastomotic technique for the renal artery, conventional end-to-end anastomosis of the renal vein, and implantation of the ureter into the bladder. This has resulted in a reproducible ischemic interval of 12-14 minutes. Plasma creatinine and histological features in animals sacrificed from 10 to 30 days after transplantation were within normal limits with no evidence of ischemic damage. A further advantage of the technique is that kidneys can be exchanged between the donor and recipient. It is recommended that this procedure, which reduces the ischemic interval by up to 50%, should be learned and employed in studies of renal transplantation in the rat, especially if such studies include the prior administration of cyclosporine, which may aggravate the effects of ischemia.
Equilibrium radionuclide angiocardiography in the detection of unsuspected mycotic aneurysms in cardiac transplantation.
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Plasma fibronectin levels during acute rejection and acute tubular necrosis in renal transplant patients.
Fibronectin (Fn), an acute phase glycoprotein synthesized by the liver, has an important immunomodulatory role. We have investigated the changes in plasma Fn in patients after renal transplantation in order to determine whether these changes predict graft injury or rejection episodes. Besides normal healthy controls, healthy pregnant controls, and a trauma control group, we used two groups of chronic renal failure patients as controls: group I, patients with end-stage renal failure (ESRF) on peritoneal dialysis; group II, patients with ESRF on hemodialysis. These were compared with two groups of renal transplant patients: group III, patients 3 months after successful renal transplantation; group IV, patients studied sequentially 10 days immediately posttransplantation. The renal transplant patients were treated with low-dose cyclosporine, azathioprine, and steroids. Citrated plasma samples were collected for Fn assay by a sandwich-type ELISA and for SDS-PAGE analysis and Western blotting. The mean plasma Fn levels were as follows: healthy controls 311.6 SEM, 13.5 micrograms/ml; healthy pregnant controls 357 SEM, 5.9 micrograms/ml; trauma controls 262.3 SEM 31.7, micrograms/ml; group I 169 SEM, 25.1 micrograms/ml; group II 199 SEM, 27.2 micrograms/ml; group III 272 SEM, 21.7 micrograms/ml; group IV 212 SEM, 27.4 micrograms/ml (day 3 postop). There was a significant difference in the plasma Fn levels on day 3 posttransplant between the patients with delayed and immediate renal function (P less than 0.03) (group IV). A significant decrease in plasma Fn levels occurred immediately after steroid therapy was stopped (P less than 0.03) in patients treated for acute rejection. Plasma Fn levels were significantly decreased in the presence of delayed graft function but did not predict rejection.
Localization of the glnD gene on a revised map of the 200-kilobase region of the Escherichia coli chromosome.
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Relationship between the dose and whole blood level of cyclosporine after liver and kidney transplantation.
Descriptions of the immunosuppression protocols used after organ transplantation typically refer to the dose of cyclosporine (on a per weight basis) given to patients. In actual clinical practice, however, the amount of cyclosporine given to patients is determined principally by the concentration of the drug present in blood. In this study we determined the correlation between the dose of cyclosporine prescribed and the level of cyclosporine achieved in stable organ recipients three or more months following successful grafting. Seventy-five adult liver transplant recipients and 65 kidney transplant recipients who survived for more than three months after the transplant and who had stable graft function were included in the analysis. The cyclosporine dose and the cyclosporine level at the first out-patient visit were recorded for each patient. The median dose of cyclosporine used in liver recipients was 15 mg/kg/day. Seventeen percent of liver transplant recipients were on a maintenance dose of cyclosporine of less than 12 mg/kg/day. Fifteen percent were on a maintenance dose of greater than 22 mg/kg/day. The median dose utilized by kidney transplant recipients was 15 mg/kg/day. Twenty-eight percent of kidney recipients were on a maintenance dose of less than 12 mg/kg/day while 9% were taking more than 22 mg/kg/day. The median whole blood cyclosporine level in liver recipients was 1025 ng/ml (range 18-1925 ng/ml). The median level in kidney recipients was 542 ng/ml (range 79-1451 ng/ml). The majority of the liver and kidney recipients had cyclosporine levels within standard "therapeutic" ranges reported for each type of transplant.(ABSTRACT TRUNCATED AT 250 WORDS)
Long-term results with conversion from cyclosporine to azathioprine at 3 months after renal transplantation.
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Initiation of a liver transplant program in South Africa.
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Public attitudes to organ donation in South Africa.
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Transplantation of solid organs in South Africa.
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Anaesthesia for liver transplantation. The Groote Schuur Hospital experience.
In October 1988 the orthotopic liver transplantation programme recommenced at Groote Schuur Hospital. The experience gained from our first 10 patients is described here. Anaesthesia for this type of surgery is demanding given the long duration of the operation and the severe haemodynamic and physiological alterations that can occur. A rapid sequence induction is usually performed and anaesthesia maintained with fentanyl and isoflurane. Dopamine and mannitol are used for renal protection. Extensive monitoring of haemodynamics, biochemistry, coagulation and temperature is essential. A rapid infusion device is mandatory as massive blood loss may occur. All patients were electively ventilated in the surgical intensive care unit postoperatively. One patient died 11 days postoperatively. The remainder are well at the time of writing.
Suicide and organ donation.
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Control theory of regulatory cascades.
We have extended Metabolic Control Theory to include cascades consisting of several modules controlling each other solely via regulatory effects. We derive several theorems that determine how the control properties of a cascade derive from (1) the control properties of each module, taken in isolation and (2) the regulatory interactions between the modules. Two cases are treated explicitly. The first concerns cascades in the absence of feed-back: in this case the internal control behaviour of each module is unaffected by external regulatory interactions. The second includes one feed-back loop and gives a quantitative expression of how feed-back modifies control properties: the internal control matrix within one module can be calculated as if the elasticity matrix of this module was the sum of its intrinsic elasticity matrix and a cyclic regulation matrix. More complex cascades can be analysed recursively by subdividing them into simpler modules, which can be treated individually. The theoretical framework developed here should facilitate quantitative experimental analysis of the control of cell physiology where the latter involves regulatory cascades.
Submucosal oesophageal varices.
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A prospective evaluation of injection sclerotherapy in the treatment of acute bleeding from esophageal varices.
In a 25 month study of massive upper-gastrointestinal hemorrhage, 64 patients were shown to have esophageal varices on emergency endoscopy. Twenty-four patients were actively bleeding from varices and were treated with a Sengstaken tube, and in 22 this was followed by emergency injection sclerotherapy using a rigid esophagoscope and general anesthesia. These 22 patients were followed prospectively and had 51 episodes of endoscopically proven active bleeding from esophageal varices which required Sengstaken tube control of hemorrhage during 36 separate admissions. This group included our total experience of injection sclerotherapy in acute variceal bleeding. The majority (14 of 22 patients) had alcoholic cirrhosis. Definitive control of variceal bleeding during the period of hospitalization was achieved in 33 hospital admissions (92%), usually with a single injection (27 hospital admissions: 75%). The results were satisfactory in 26 hospital admissions (72%). There were nine deaths (41% overall patient mortality rate), but no patient died primarily of variceal bleeding, and exsanguinating variceal bleeding was no longer a problem. The mortality rate per injection was 18%, and the mortality rate per hospital admission was 25%. Injection sclerotherapy is proposed as the emergency treatment of choice for patients with proven bleeding esophageal varices who do not stop bleeding on initial conservative treatment.
A prospective controlled trial of sclerotherapy in the long term management of patients after esophageal variceal bleeding.
The preliminary results of the first 25 months of a prospective randomized controlled clinical trial, designed to compare repeated injection sclerotherapy with conservative medical management in the long term treatment of all patients shown to have previously bled from esophageal varices, are presented in detail. To date, 31 patients have been randomized, 15 in the chronic injection group and 16 in the control medical management group. In addition, five patients excluded for geographic reasons have been injected out of trial. Ethanolamine oleate has been injected into the varices, using a modified rigid esophagoscope under general anesthesia. The preliminary results have been encouraging. It has been possible to eradicate esophageal varices in the chronic injection group and, once the varices had been eradicated, no patient had recurrence of variceal bleeding. On the other hand, recurrent variceal bleeds have remained a continuing problem in a number of the patients in the control study. A longer follow-up period will be required to assess both the quantitative and the qualitative aspects of survival and to determine how long esophageal varices will remain eradicated as well as how frequently repeated injections will be required.