Ultrastructural changes produced in dorsal root ganglia in vitro by exposure to ethylene oxide from hemodialyzers.

Ethylene oxide (EO) gas, used to sterilize hemodialysis equipment, is a known neurotoxin and residual gas remains in dialyzers after airing. If tissue culture medium is incubated in dialyzers and then rat dorsal root ganglion (DRG) cultures are exposed to this medium, characteristic changes occur. These include axonal swellings and the death of neurons after five days. Electron microscope findings were compared between DRG grown in control medium containing 10% calf serum, DRG incubated in the same medium exposed to the blood compartment of capillary flow or plate dialyzers and DRG grown in medium supplemented with 10% dialysis patient serum. Electron microscope findings included frequent axonal swellings with the accumulations of membrane bound vesicles and the apparent disruption of microtubules. There were also conspicuous accumulations of membrane bound vesicles, dense bodies, myeloid figures, and areas of vesicular degeneration in Schwann cells. These changes were seen with dialyzer exposed medium or with medium containing patient serum but not with controls or with medium incubated in plate dialyzers. The changes were similar to those reported in nerve biopsy specimens from patients with known EO neuropathy.

Deferoxamine-enhanced fecal losses of aluminum and iron in a patient undergoing continuous ambulatory peritoneal dialysis.

Aluminum-associated osteomalacia and transfusion-induced hemosiderosis developed in an anephric patient receiving long-term maintenance treatment with continuous ambulatory peritoneal dialysis. Intravenous administration of 1.0 g of deferoxamine led to marked increases in the fecal elimination of aluminum and iron. Dialysate removal of these same metals also increased but to a lesser extent. This indicates that the biliary/fecal route of excretion may contribute significantly to deferoxamine-induced losses of aluminum and iron in patients undergoing continuous peritoneal dialysis.

A four-year comparison of continuous ambulatory peritoneal dialysis and home hemodialysis: a preliminary report.

All patients who received initial dialysis therapy by either continuous ambulatory peritoneal dialysis (CAPD) or home hemodialysis between January 1979 and January 1983 were retrospectively compared for adequacy of dialysis, morbidity, and survival. In this study group, 30 patients had home hemodialysis and 21 patients had CAPD; the mean ages of the patients in these two groups were comparable. Both methods of treatment provided adequate dialysis, as shown by results of serial laboratory studies. The number of days of hospitalization per year at risk was twice as great for the patients on CAPD as for those on home hemodialysis; peritonitis was responsible for this difference. The survival was similar in both groups at 32 months of therapy. Death was clearly related to coexisting morbid events other than dialysis in the home hemodialysis group; however, one of the two deaths in the group on CAPD seemed to be indirectly related to the treatment of peritonitis. These findings suggest that CAPD, when compared with hemodialysis, (1) provides adequate dialysis, (2) is accompanied by greater morbidity (hospitalization), and (3) may introduce a morbid event (peritonitis) that may adversely affect survival.

Elevated bone aluminum content in dialysis patients without osteomalacia.

In almost all dialysis patients, bone aluminum content (BAC) is elevated in comparison with levels in normal subjects. Extremely high BAC (200 micrograms or more of aluminum per gram of bone) is significantly associated with classic aluminum-related osteomalacia. We noted three patients with elevated BAC but without histologic evidence of typical osteomalacia. Two of the patients had moderately severe osteitis fibrosa (hyperparathyroidism), and one patient had mixed uremic bone disease--predominantly hyperparathyroidism but some impairment of bone mineralization as well. As has recently been reported by others, the deferoxamine infusion test yielded unusual results in these patients. On the basis of our observations, we believe that an isolated measurement of BAC to determine whether aluminum-related osteomalacia is present has certain limitations. Aluminum-related bone disease can be accurately diagnosed only with use of bone histomorphometry. Elevated levels of immunoreactive parathyroid hormone may offer protection from the toxic effects of aluminum.

Acute renal failure treated by slow continuous ultrafiltration. Preliminary report.

We report our initial experience with the use of slow continuous ultrafiltration in the treatment of acute renal failure. Advantages of slow continuous ultrafiltration over conventional hemodialysis are greater blood pressure stability, no need for systemic anticoagulation, augmented fluid input and removal, and enhanced ease of operation. Our results in two patients confirm other reports that this method can be successfully performed in hemodynamically unstable patients with acute renal failure.

Renal toxicity during therapy with gentamicin or tobramycin.

Twenty-seven patients who had normal pretherapy renal clearance by the [125I]iothalamate test were randomly assigned either gentamicin or tobramycin for therapy of infections due to susceptible bacteria. No patients were critically ill or had evidence of bacteremia. Mean age and duration of therapy were 51 years and 14 days, respectively, for 15 patients treated with gentamicin, and 45 years and 13 days for 12 patients treated with tobramycin. At the completion of therapy, six (40%) gentamicin and seven (58%) tobramycin patients had a decrease in renal clearance of at least 14% below baseline. The mean decrease was 26% in the gentamicin group and 23% in the tobramycin group. Simultaneous increases in serum creatinine concentrations (greater than or equal to 0.2 mg/dl) occurred in only 4 (31%) of the 13 patients. Of four patients who had renal clearance studies repeated 3 weeks to 6 months after therapy, two had stable function, but at 16 to 19% below baseline. Mean urinary concentration of N-acetyl glucosaminidase and alanine aminopeptidase increased faster and to higher levels with gentamicin than with tobramycin. However, on an individual patient basis, they were not predictive of a decrease in renal clearance in either therapy group.

Chronic peritoneal dialysis in juvenile-onset diabetes mellitus: a comparison with hemodialysis.

Fourteen juvenile-onset diabetic patients accepted for renal transplantation and maintained on chronic peritoneal dialysis during a 3-year period were compared with a similar group of 43 patients accepted for renal transplantation and maintained on hemodialysis. The 1-year survival in each group was similar (52% on chronic peritoneal dialysis; 55% on hemodialysis), but there was a striking difference in progressive morbidity. Seven patients on chronic peritoneal dialysis were blind in one or both eyes at the onset, and visual acuity improved in two, including one bilaterally blind patient who achieved 20/35 vision bilaterally; none worsened. In the hemodialysis group, 12 patients were totally blind in one or both eyes and 11 additional patients became blind or had severe deterioration in vision; none improved. Neuropathy progressed in only 1 patient on chronic peritoneal dialysis, whereas it worsened in 17 patients on hemodialysis--9 to the extent that they needed braces or canes or were nonambulatory. All patients on chronic peritoneal dialysis were home trained and were dialyzed at night, with seven being able to work full or part time; virtually none of the patients on hemodialysis were able to work. Chronic peritoneal dialysis was relatively free of technical complication, and no significant difficulty was encountered in diabetic control, in the anephric state, or during abdominal surgery. Chronic peritoneal dialysis appears to have less associated morbidity than does hemodialysis in the treatment of chronic renal failure of juvenile-onset diabetes mellitus.

Accuracy of antibody-coated-bacteria test in recurrent urinary tract infections.

Antibody coating of urinary bacteria was compared with results of ureteral catheterization studies in order to localize the site of recurrent urinary tract infections in 32 patients. The antibody-coated-bacteria test reliably detected infections in patients with upper urinary tract infection (16 of 17 patients), but false-positive results occurred frequently in patients with lower urinary tract infection (5 of 15 patients). The antibody-coated-bacteria test appears to be a useful screening test for localization of infection in patients with recurrent urinary tract infections.

Clinical features and management of cystinuria.

Cystinuria is a complex hereditary disorder that affects both sexes with equal frequency and severity. Symptoms usually begin early (children and young adults) but may develop at any age. Stature is normal and there are no clinical nutritional abnormalities. The morbidity of cystine urolithiasis is considerable. Hyperuricemia is a frequent associated finding and is probably the result of multiple factors. No other abnormalities are consistently related to this disease. Treatment with adequate oral fluids to ensure a copious urine volume and with oral alkali to keep the urine alkaline is most successful when used prophylactically in the stone-free patient. However, dissolution of existing calculi is unlikely with this regimen alone. The addition of D-penicillamine often results in dissolution of stones and prevention of recurrent calculi in patients who have continued stone growth despite the use of oral fluids and alkali. Because toxic reactions with D-penicillamine are frequent and sometimes severe, this drug should be used only when necessary and then as an adjunct to rather than a substitute for increased oral fluids and alkali. Failure of treatment in spite of adequate therapy should alert the physician to the possibility of coexisting complicating problem.

Coronary artery bypass operation in dialysis patients.

To analyze the short- and long-term morbidity and mortality among maintenance dialysis patients who have undergone coronary artery bypass operations, we identified 25 such patients at the Mayo Clinic and three recently published large single-center studies that provided sufficient detail for meaningful comparison. Two independent observers reviewed the new information with regard to pertinent historical, clinical, and laboratory data. The perioperative mortality was 20%. Among the perioperative survivors, 1- and 2-year survival rates were 95% and 77%, respectively. The 3-year actuarial survival was 70%. Uniformly, the symptoms diminished, and the need for antianginal medication was decreased. In the three other large published series, the perioperative mortality ranged from 3 to 20%, and coronary artery bypass performed earlier after the onset of the symptoms seemed to result in a lower perioperative mortality. We conclude that elective coronary artery bypass in dialysis patients is associated with acceptable short-term morbidity and mortality and effective relief of symptoms. Surgically treated patients may have a survival advantage. Thus, we advocate aggressive early investigation and surgical treatment of these patients.

Postdilution hemofiltration in the management of acute hepatic failure: a pilot study.

We conducted a pilot study to assess the feasibility and efficacy of postdilution hemofiltration (PDHF) in the management of acute hepatic failure. From January 1984 through May 1986, we encountered seven patients with acute hepatic failure and entered these consecutive patients in the study; three had non-A, non-B hepatitis and one each had type B hepatitis, fulminant Wilson's disease (hepatolenticular degeneration), acute allograft (liver) failure, and acute fatty liver of pregnancy. Two of these seven patients were unable to undergo PDHF because of a precarious hemodynamic status. Of the five patients treated with PDHF, four had amelioration of hepatic encephalopathy; in two of these patients, a close temporal relationship was noted between the improvement and the procedure. Four patients had appreciable thrombocytopenia related to PDHF and bleeding complications. Our preliminary results support a possible role for PDHF as a temporary artificial liver support system for patients with acute hepatic failure.

Erosive spondyloarthropathy in long-term dialysis patients: relationship to severe hyperparathyroidism.

We describe the development of a destructive, erosive spondyloarthropathy in three long-term dialysis patients (mean duration of dialysis, 96 months). In all three patients, the lesions caused symptomatic vertebral pain and developed during a period of only a few months. All patients had extremely elevated levels of immunoreactive parathyroid hormone, and two patients had evidence of severe hyperparathyroidism on bone biopsy specimens. Two patients who underwent subtotal parathyroidectomy had rapid relief of symptoms and no further radiographic evidence of progression of the spondyloarthropathy. The third patient refused subtotal parathyroidectomy and had pronounced progression of the destructive spondyloarthropathy in the cervical spine. The limited experience of others, along with our currently reported findings, strongly suggests that hyperparathyroidism plays a major role in the development of this disorder. Erosive spondyloarthropathy is increasingly recognized in long-term dialysis patients and may be a unique clinical and radiographic manifestation of severe hyperparathyroidism in this population.

Results of treatment of center hemodialysis patients.

Four hundred eighty-three patients were maintained by hemodialysis in an outpatient hemodialysis center at the Mayo Clinic between 1963 and 1977. Although only 18 patients had experienced a myocardial infarction and 6 had had a cerebral infarction before beginning dialysis, 30 subsequently had acute myocardial infarction and 45 had a stroke. These two complications accounted for 48 of the 98 deaths that occurred during maintenance dialysis. Despite such complications, 183 patients were employed, 124 remained active at home or at school, and 115 were totally disabled. Survival of patients maintained solely by dialysis was 52% at 5 years. For the group as a whole, including patients who received their first allograft, the survival rate at 5 years was 65%.

Continuous ambulatory peritoneal dialysis. Three years' experience at the Mayo Clinic.

From January 1979 through January 1982, 69 patients with end-stage renal failure of various causes were treated by continuous ambulatory peritoneal dialysis. The dialysis was adequate and stable in all except four patients; two of these four became irreversibly uremic, and the other two had inadequate ultrafiltration. Hemoglobin levels increased initially and remained stable in all but two patients. In our experience, metabolic problems included control of secondary hyperparathyroidism, adequate protein nutrition, progressive neuropathy, abnormal lipoprotein profiles, and excessive weight gain. Technical problems included recurrent peritonitis, maintenance of adequate peritoneal access, and development of abdominal hernias. In general, all but two patients remained enthusiastic about this type of therapy despite inherent problems. The long-term potential of continuous ambulatory peritoneal dialysis remains uncertain at this point, but for most patients, adequate short-term treatment by this method is a reasonable alternative to hemodialysis.

Results of treatment of renal failure by means of home hemodialysis.

Of 630 patients who began hemodialysis treatment for chronic renal failure between 1965 and 1977, 147 successfully completed training for home hemodialysis. Patient compliance was satisfactory, as reflected by the results of monthly blood chemical values, hematocrits, and weight gain between dialysis. Although only 15 patients had previous myocardial infarctions and 4 had had strokes before beginning dialysis, 9 patients subsequently experienced acute myocardial infarctions and 14 had strokes. Of the 45 patients who died while being maintained by hemodialysis, 24 had cardiopulmonary complications and 6 had strokes. Despite such complications, 70 patients were gainfully employed and 32 were active at home or at school, whereas 29 were totally disabled. At last follow-up, 74 remained on home hemodialysis, 53 had functioning renal allografts, and the rest of the patients were being maintained in our dialysis center, had transferred elsewhere, or were being maintained by peritoneal dialysis. The overall estimated 5-year survival rate was 56%, whereas the estimated 5-year survival rate for those maintained by home hemodialysis alone was 52%.

Use of combined plasmapheresis and immunosuppression in the treatment of Goodpasture's syndrome.

Five consecutive patients with well-documented Goodpasture's syndrome were treated with plasmapheresis and immunosuppression. In all patients, the antiglomerular basement-membrane antibody titers decreased with treatment. In three patients, hemoptysis responded promptly to plasmapheresis. Two patients presenting with severe renal failure required chronic dialysis, and three patients who had serum creatinine levels less than 2.1 mg/dl before treatment improved or had stabilization of their renal function. We confirm that the use of plasmapheresis and immunosuppression is a promising method of treatment in some patients with Goodpasture's syndrome.

Recurrent Goodpasture's syndrome.

A 49-year-old woman had three distinct episodes of pulmonary hemorrhage over a 11-year period separated by symptom-free intervals of 6 and 5 years. The first and third episodes were associated with mild glomerulonephritis and linear deposition of IgG along glomerular/tubular basement membranes. The first episode was associated with a rising influenza A2 titer. Investigation of the third episode revealed circulating antiglomerular basement membrane antibodies detected by radioimmunoassay but not by indirect immunofluorescence. Antilung basement membrane antibodies were detected by both direct and indirect immunofluorescence. Recovery from each hemorrhage followed blood transfusion and oxygen therapy. This case demonstrates that (1) Goodpasture's syndrome, predominantly manifest by pulmonary hemorrhage, may have circulating antibodies with greater affinity for lung membrane compared with glomerular basement membrane, and (2) the antiglomerular basement membrane antibody response is not necessarily an acute self-limited event but may be a chronic or recurrent phenomenon.

Interpretation of serum aluminum values in dialysis patients.

To determine the significance of serum aluminum levels in dialysis patients, the authors retrospectively analyzed a series of patients on maintenance hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). All patients had always been treated with a dialysate containing negligible amounts of aluminum. The serum aluminum levels of hemodialysis and CAPD patients were not significantly different, not related to age or sex, and not affected by the presence of diabetes or vitamin D intake. The most important determinant of serum aluminum level in the hemodialysis patients was the current dose of aluminum-containing phosphate-binding medication. This relationship was most striking in the compliant patients. In hemodialysis patients, after an increase during the first one to two years, the aluminum levels plateaued. Aluminum levels remained stable more than five years in CAPD patients. Red blood cell mean corpuscular volume was negatively correlated with serum aluminum level. In 28 dialysis patients who had bone biopsy, aluminum levels were positively correlated to histochemical aluminum staining and bone aluminum content. A level greater than 100 ng/mL was a reliable indicator of aluminum-associated osteomalacia, although a lower level did not exclude the presence of low turnover bone disease or mixed uremic osteodystrophy--two disorders possibly related to aluminum. In the presence of a high serum aluminum, elevated levels of immunoreactive parathyroid hormone (iPTH) were useful in detecting the presence of hyperparathyroidism; low levels of iPTH did not allow the authors to distinguish between other subtypes of uremic osteodystrophy.

The pharmacokinetics of racemic verapamil in patients with impaired renal function.

The pharmacokinetics of verapamil were studied in patients with renal failure who were undergoing maintenance hemodialysis and in normal subjects after an IV infusion of 10 mg and a single oral dose of 120 mg. Plasma levels of verapamil and its active metabolite, norverapamil, were analyzed by a sensitive and specific HPLC procedure. Severe renal failure requiring hemodialysis did not change the time course of verapamil and norverapamil plasma concentrations after either the IV or oral dose. The terminal elimination rate constant, clearance, volume of distribution, and bioavailability of verapamil were not significantly different between the two groups of subjects. In addition, the apparent maximal plasma concentration, terminal elimination rate constant, and area under the curve for norverapamil were similar in patients with renal failure and normal subjects. The study showed that the plasma disposition of verapamil and norverapamil was not affected in patients with impaired renal function. Furthermore, this study does not indicate that any change in dosage is necessary when single doses of verapamil are administered to patients with renal failure.

A comparison of two surgical techniques for performing mastectomy.

Most surgeons performing mastectomy (MRM) use either the scalpel or electrocautery for developing flaps and performing node dissection. We report a retrospective analysis of all MRM performed over a five-year period by two surgical oncologists. One-hundred-and-ninety-six cases met criteria for inclusion into the study. There are 110 patients in the electrocautery (EC) group and 86 patients in the scalpel (Scpl) group. Mean patient age, mean specimen weight and mean number of lymph nodes removed were not significantly different for the two groups. The incidence of complications was similar for the two groups. Mean estimated blood loss was 134.1 cc for the EC group and 331.6 cc for the Scpl group (P < 0.001). Estimated blood loss ranged from 25 to 475 cc for EC group and from 88 to 1350 cc for the Scpl group. One patient in the Scpl group required transfusion. Mean operating time was less for the Scpl group, 111.0 vs 93.5 minutes (P < 0.009). Multiple regression analysis revealed that technique was the strongest predictor of estimated blood loss (standardized coefficient 0.61). Operating time, age, number of nodes removed and specimen weight were less predictive (standardized coefficient 0.21, 0.17, 0.11 and 0.09, respectively).