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.
Primary sclerosing cholangitis.
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Demographic factors influencing consent for cadaver organ donation.
The records of all donor referrals to Groote Schuur Hospital over a 5 1/2-year period were retrospectively examined to determine which factors influenced the families' decision on organ donation. In 35% of these referrals the families were not approached for consent. The reasons for this included the potential donor being unsuitable for organ donation or not meeting all the criteria for brain death. The effects of the age, sex, race and the cause of death of the potential donor on whether the family gave consent were investigated. This study demonstrates that consent was given more readily when the potential donor was aged less than or equal to 10 years, that the sex of the potential donor appeared to have no effect on the decision by the family about organ donation, that black families gave consent for organ donation less frequently than families of other race groups and that consent was obtained more easily when death was due to suicide.
Radionuclide ventriculography in severely underweight anorexia nervosa patients before and during refeeding therapy.
Congestive heart failure is a well-recognized complication of refeeding therapy in underweight patients with anorexia nervosa but there are few data describing cardiac function during the critical refeeding period. This prospective study examined left ventricular function with conventional electrocardiographic-gated radionuclide ventriculography (RVG) in severely underweight anorexia nervosa patients both before and during refeeding therapy. Eight patients underwent rest and exercise RVG at admission and after regaining approximately 5% to 10% of their ideal body weight. With the admission study serving as a control, the left ventricular ejection fraction and regional wall motion analysis were analyzed before and after refeeding and weight gain. Resting left ventricular ejection fractions were not significantly different between the first and second RVGs (64 +/- 11% vs. 62 +/- 8%, respectively; P greater than .05). Likewise, the left ventricular ejection fraction with maximal exercise did not significantly differ when comparing the first or the second RVG (74 +/- 10% vs. 72 +/- 8%, P greater than .05). During the baseline RVG, the left ventricular ejection fraction increased from 64 +/- 11% (rest) to 74 +/- 10% (maximal exercise) (P less than .001). During the second RVG, the ejection fraction increased from 62 +/- 8% (rest) to 72 +/- 8% (maximal exercise) (P = .003). However, the left ventricular exercise ejection fraction in the second RVG in one patient increased only by one absolute percentage point. Four of the eight patients had regional wall motion abnormalities detected during resting and/or exercise RVG. Abnormal cardiac function occurs in asymptomatic patients with anorexia nervosa undergoing refeeding therapy.
Modular structure of FixJ: homology of the transcriptional activator domain with the -35 binding domain of sigma factors.
The FixL/FixJ two-component system is a global regulator of nitrogen-fixation genes in Rhizobium meliloti. The transcriptional activator FixJ contains two modules: its N-terminal module is homologous with other two-component regulators; its C-terminal module shows homology with various transcriptional activators, and with the C-terminal region of sigma factors, which is involved in the discrimination of the -35 region of bacterial promoters. We show that the C-terminal module of FixJ contains the entire transcription activation function, and that the N-terminal module regulates this activity negatively. Oligonucleotide-directed mutagenesis of the transcriptional activator module demonstrated the importance of a potential helix-turn-helix structure.
Improved method of porcine renal allografting for transplantation research.
This study presents a refined, reproducible, and clinically appropriate animal model of renal transplantation. A pair of kidneys are harvested from a donor pig and preserved in Euro-Collins' solution (4 degrees C). After a set period of preservation, the allografts are transplanted to two recipient pigs. The abdomen is entered through a midline incision. The right common iliac artery and vein are dissected and bilateral native nephrectomy is performed. Each allograft is then randomly assigned and transplanted to the recipients. Three minutes before unclamping, 100 mg of furosemide and 10 g of mannitol are given IV. Immediately after reperfusion, urine output is measured for 1 h. The allograft is biopsied and ureteroneocystostomy is created. Cystostomy is then placed using a 16F Foley catheter. The bladder neck is ligated to secure complete diversion of urine, and the abdomen is closed in layers. This kidney transplant model allows an absolutely paired study of the kidney allograft function from the same donor and also collection of pure urine at any time postoperatively, obviating the need for metabolic cages or sedation for urinary collection. This model and its unique modifications allow various transplant studies, including organ preservation, immunosuppressive protocol, and the prevention of reperfusion injury from oxygen free radicals.