Biomedical subjects
Publications and source records attributed to J H Sadler.
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Glycosuria, hyperglycemia, and nephrotic-range proteinuria developed in a 68-year-old patient after clonidine was added to a stable antihypertensive regimen, which included metoprolol, of three years' duration. He later became glucose-intolerant with fasting hyperglycemia. Clonidine has been reported to transiently impair glucose tolerance. Persistent diabetes in a previously normoglycemic patient following clonidine has not been reported, and it supports the possibility that clonidine and metoprolol may have additive effects in suppressing endogenous insulin secretion.
A case report of marked peripheral blood eosinophilia and eosinophilic infiltration of a rejected renal allograft in a transplant recipient stimulated our review of the clinical course of 132 consecutive renal transplant recipients. A total of 187 acute rejections occurred in 112 patients. Diagnosis was made by renal biopsy in 124 cases. The percentage of eosinophils in the leukocyte differential of patients with irreversible rejection was 5.2 +/- 5.7 (mean +/- SD) versus that seen in patients with reversible rejection, 2.9 +/- 3.5 (P less than .05). The difference in the total eosinophil counts in each group was not statistically significant. Patients with peripheral blood eosinophil percentages greater than or equal to 4% had a 37.9% irreversible rejection rate, whereas those who had less than 4%, had a 22.4% loss rate (P less than .01). Six of seven patients with greater than or equal to 2% eosinophils in the inflammatory infiltrate of their renal allograft lost their kidney, whereas grafts with less than 2% eosinophils had a 36.8% loss rate (P less than .02). We conclude that the increased presence of eosinophils in the peripheral blood and/or renal allograft biopsy specimen is an adverse prognostic factor for acute rejection outcome.
The predictive value of peripheral blood T cell subset monitoring in renal allograft recipients has been questionable, and there has been no information concerning the correlation of T cell subset changes with the clinical event related to cyclosporine nephrotoxicity. This study was conducted to investigate the clinical usefulness of serial T cell subset monitoring in 34 consecutive renal transplant patients treated with cyclosporine by determining the total peripheral lymphocyte count and T cell subset counts using Leu-4, Leu-3ab, and Leu-2a monoclonal antibodies and flow cytometry up to 6 months after transplantation. The absolute counts of all cells were lower in transplanted patients than those of normal controls, but were not different from those of hemodialysis patients. During infection, the helper/suppressor (H/S) ratio and the cell counts, except for suppressor cells, decreased significantly. Within one week prior to rejection, all cell counts also decreased significantly. Furthermore, cell counts before steroid-resistant rejection were significantly lower than those before steroid-responsive rejection. In contrast, lymphocyte and T cell counts were increased significantly within one week prior to cyclosporine nephrotoxicity being diagnosed; the H/S ratio was not correlated with rejection or toxicity. These results indicate that H/S ratio is not associated with clinical events of renal allograft recipients, but serial lymphocyte and T cell subset counts can provide valuable information for the differentiation of rejection from cyclosporine nephrotoxicity, and also for predicting the outcome of the allograft rejection.
A mouse monoclonal antibody, specific for binding with the epithelial surface antigen in human renal proximal tubules, was produced by hybridoma culture. Using this antibody, an enzyme-linked immunosorbent assay was developed to measure the human renal tubular epithelial antigen (HRTE) concentrations in serum samples from 25 normal subjects and 66 consecutive renal allograft recipients. In 46 patients treated with azathioprine and prednisone, serum HRTE was elevated more than two-fold in 56 of 62 rejection episodes 2-5 days before the clinical diagnosis was made. Of the 56 rejection episodes, the antigen level fell to baseline after treatment in 44 steroid-responsive episodes, but it remained elevated in 8 steroid-resistant rejections, and it became undetectable 3-4 days after the initial elevation in 4 episodes in which allografts were lost to rejection. In 20 patients treated with cyclosporine and prednisone, all 25 rejection episodes demonstrated a greater than two-fold increase of serum HRTE 1-6 days prior to the diagnosis of rejection. The antigen level fell to baseline in 23 reversible rejection episodes, however serum HRTE remained elevated in 2 steroid-resistant patients whose grafts were lost to rejection. Cyclosporine nephrotoxicity without rejection was confirmed in 6 episodes, each of which demonstrated a more than two-fold increase in HRTE 2-4 days before toxicity was diagnosed. When the cyclosporine dose was reduced, the antigen level decreased as the serum creatinine declined. Serial determinations of serum HRTE in renal transplant recipients can provide valuable information for the early diagnosis and management of allograft rejection and cyclosporine nephrotoxicity.
We have evaluated the Hickman catheter and Hemasite access port as means to re-establish vascular access in patients lacking veins for conventional arteriovenous fistulae. The Hemasite is more convenient, but is also costlier, requires more surgical skill to implant, and is more frequently associated with major infections. One-half of the Hemasites have failed because of infection. As a result, the long-term survival rate is lower for Hemasite graft, although the differences noted have not yet reached statistical levels of significance.
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Experience with 35 needleless implants (Hemasite) in 27 patients over the past 27 months has shown that this device can provide immediately available painless access in patients lacking adequate veins for a direct internal fistula for hemodialysis. The cumulative patency rate of 46% at two years is comparable to that of polytetrafluoroethylene grafts. The major complication was infection which contributed to graft loss in one third of patients. Obese female patients were particularly susceptible to infection and had a worse graft prognosis. Long-term results with a graftless model were poor.
This report presents the first description of direct peripheral nerve compression as a complication of brachial artery-basilic vein vascular access in patients with uremia who are receiving long-term hemodialysis. Three patients are presented. An expanding basilic vein hematoma compressed the radial nerve in one patient. A graft associated abscess adjacent to the brachial artery compressed the median nerve in a second patient. A basilic vein aneurysm compressed the median nerve in a third patient. In two cases, electrodiagnostic studies were helpful in identifying the location and severity of the peripheral nerve dysfunction, and in excluding more common distal nerve dysfunction, which is sometimes seen in these patients as a result of circulatory alterations in the extremity caused by dialysis. Prompt surgical decompression led to significant recovery of nerve function in all three patients. It is concluded that direct peripheral nerve compression is a rare complication of brachial artery-basilic vein vascular access in patients with uremia who are receiving long-term hemodialysis.
Prompted by previous reports of substantial clinical improvement in most schizophrenic patients given hemodialysis for their psychiatric condition, we studied the efficacy of hemodialysis in 15 schizophrenic outpatients, under double-blind, controlled conditions. The patients were randomly assigned to either a real-sham or sham-real sequence of dialysis treatment. Results of repeated measurement and other analyses of data on symptoms and behavior that were collected before study treatment, at crossover, and at the end of treatment revealed no difference between the effects of real and sham dialysis. These results provide important experimental evidence of the lack of therapeutic efficacy of hemodialysis in schizophrenia.
Bretylium kinetics were examined in patients with varying degrees of renal impairment after a single intravenous dose of bretylium tosylate. Maximum plasma concentrations achieved at the end of the infusion, when normalized to the dose, correlated strongly with creatinine clearance. Drug disposition from plasma was biexponential, with a short distributive phase, but drug elimination was reduced, especially in patients with creatinine clearance below 30 ml/min X 1.73 m2. There was reduction in renal and total clearance and prolongation of t 1/2, with deteriorating renal function. In one patient who was reevaluated after a year, there was 76% reduction in the total clearance, corresponding to 43% deterioration of renal function. The difference of 33% between these values is due to a reduction of nearly 36% in volume of distribution, caused by the further deterioration of the renal function. Six-hour hemodialysis procedure on two anephric patients, resulted in an apparent one- to threefold increase in the computed bretylium clearance during dialysis, but the fraction of the total body load eliminated during the same period was not proportionally significant. The strong linear relationships between renal and total clearance, beta, and the creatinine clearance, may be helpful in adjusting dosage regimens for bretylium in patients with renal dysfunction.
Open-trial reports of substantial clinical improvement in most schizophrenic patients on hemodialysis for their psychiatric condition prompted the present study to determine the efficacy of hemodialysis under double-blind, controlled conditions. Fifteen schizophrenic outpatients were randomly assigned to either a real-sham or sham-real dialysis treatment sequence. Presented in detailed, graphic form, results of repeated measurement and other analyses of symptom and behavioral data collected initially, at crossover, and at the end of treatment revealed no differential effects between real and sham dialysis. These results provide important experimental evidence of the lack of therapeutic efficacy of hemodialysis in schizophrenia.
The effect of dietary therapy on the serum lipid profile was examined in 32 post-transplant patients. Patients were transplanted more than 4 months before the study and had stable renal function and no other condition affecting lipid metabolism. Serum lipid profiles were determined on two serum samples obtained after a 12-hour fast. Seventeen patients who had pre-transplant hyperlipidemia (HLP) had similar HLP after transplantation. Of the 14 patients with normal pre-transplant profiles, 9 remained normal and 5 developed HLP. Twelve patients with HLP received out-patient dietary therapy providing less than 500 mg of cholesterol, less than 35% of calories from fat, less than 50% of calories from carbohydrate, and a P:S ratio greater than 1. Maintenance calories were based on the Harris-Benedict standard except for 9 overweight patients who were given less. After 3 months of therapy, serum cholesterol and triglycerides decreased to normal in 8 of 9 patients in whom both were elevated before dietary treatment and were unchanged in one patient. In 3 patients who had normal triglyceride but elevated cholesterol levels before therapy, cholesterol decreased but remained above normal; triglyceride increased in one patient and remained normal in two. High-density lipoprotein cholesterol (HDL-C) increased in all 12 patients and became normal in 11. Body weight fell in 11 of 12 patients receiving dietary therapy. Cholesterol, triglyceride, and HDL-C remained unchanged in 11 patients who did not undergo dietary treatment. Dietary therapy is a safe and effective way to treat post-transplant HLP.
Three kidneys preserved as though for transplantation became available for study. The clinical details relating to the donors and methods of preservation by simple hypothermia and pulsatile perfusion are presented. Light microscopic and ultrastructural features observed following perfusion fixation of the kidneys are described. All three kidneys showed some reversible ischemic cell damage, but only one showed evidence of ischemic cell damage that was considered to be irreversible. The latter was seen focally in the pars recta of the proximal convoluted tubules and in the ascending thick limb of the loop of Henle. The irreversible changes were present in the kidney that had undergone the longest period of simple hypothermic storage prior to transfer to pulsatile perfusion preservation. The similarity of the findings to those seen in vivo in the rat after one hour of total renal ischemia, followed by 24 hours' reflow, is discussed; a hypothesis is suggested to explain the site of the irreversible injury seen in the kidneys under study.
A 28-year-old long-distance runner experienced fever, chills, and brown urine 24 hours after a six-mile run. This was accompanied by a large rise in the creatine phosphokinase level and a rise in echovirus 9 titers from 1:16 to greater than 1:256 during a two-week period. A muscle biopsy specimen showed acute rhabdomyolysis, but no viral inclusion particles. Muscle energy metabolism analysis demonstrated no abnormalities. The patient was treated with forced saline diuresis, and he maintained normal renal function. He subsequently returned to long-distance running and has remained well for one year after the episode. This represents the first reported case, to our knowledge, of acute rhabdomyolysis associated with an echovirus 9 infection.
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To determine whether perfusion preservation affected the structure and survival of kidney transplants, we correlated clinical and histologic data in 77 kidneys biopsied one hour after transplantation. Twenty-one of 36 perfusion-preserved kidneys had a glomerular capillary lesion suggestive of intravascular coagulation. None of 41 kidneys preserved by hypothermia alone had this lesion. Presence of the lesion did not correlate with donor or recipient characteristics, warm or cold ischemia time, HLA match, percentage of preformed lymphocytotoxic antibody titers or perfusion characteristics. Of 21 transplants with the lesion, nine required nephrectomy by one month, and one-month serum creatinine was less than 2.0 mg per deciliter in only three of the remaining 12 transplants. We conclude that perfusion preservation may cause pathologic changes that may adversely affect kidney-transplant function. The causes of the pathologic process remain unclear.
A new vascular access for chronic hemodialysis is developed by creating a fistula in the upper arm between the end of the relocated basilic vein and anterior aspect of the brachial artery. The procedure has been used 24 times in 23 patients over the past 15 months (average eight months) with minimal complications and low failure rates. This fistula provides a straight, long, easily accessible conduit with high flows; it has only one vascular anastomosis and maintains the anatomic continuity of its venous end with the axillary vein. It also obviates the need for autologous, prosthetic, or heterografts. The procedure is indicated when suitable vessels in the forearm have been exhausted or are unavailable. However, additional clinical trials and continued long-term follow-up are necessary for more definite conclusions.