Biomedical subjects
Publications and source records attributed to J T McCarthy.
Myeloid metaplasia associated with idiopathic myelofibrosis most commonly involves the reticuloendothelial organs, such as the spleen, liver and retroperitoneal lymph nodes. We report on a patient with myeloid metaplasia (extramedullary hematopoiesis) of the renal pelves, ureters and bladder. The pathogenesis, clinical characteristics, treatment and prognosis of this condition are discussed.
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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.
Simulated hemodialysis with isotonic saline was performed to compare the requested blood flow rate (BFR-r) with the actual blood flow rate (BFR-a) delivered during rapid, efficient hemodialysis. Four different blood pumps and blood lines from three different manufacturers were used for the studies. BFR-r was set on each blood pump, and a timed outflow specimen from the dialysis circuit was used to measure the BFR-a delivered. BFR-r values of 200, 350, and 500 mL/min were used; the arterial pressure was set at -50, -250, and -325 mm Hg. BFR was determined every hour for 5 hours. At an arterial pressure of -50 mm Hg, the BFR-a was slightly higher than the BFR-r, and this did not vary over the 5-hour study period. When the arterial pressure was -250 mm Hg, the initial BFR-a was 95% of the BFR-r; at the end of the 5-hour study, this had declined to an average of 87% of the BFR-r. The largest discrepancy between BFR-a and BFR-r was at an arterial pressure of -325 mm Hg; the initial actual values averaged only 90% of the requested, and by the end of the 5-hour study, this value had declined to a mean of 78% of the BFR-r. The use of whole blood with a hematocrit value of 33% and the addition of venous resistance did not significantly affect these results.(ABSTRACT TRUNCATED AT 250 WORDS)
Forty-eight dialysis patients undergoing bone biopsy were analyzed for clinical history, blood biochemical values, bone histologic findings, bone aluminum content (BAC), bone iron content (BIC), bone iron stores, and histochemical staining of bone aluminum and bone iron. Four patients had significant trabecular bone iron staining alone; eight patients had significant bone iron and bone aluminum staining; 13 patients had significant bone aluminum staining alone; and 23 patients showed no significant bone aluminum or iron staining. Patients with significant bone iron staining were younger (37.4 +/- 5.3 years v 53.2 +/- 2.3 years, P less than 0.01, mean +/- SEM) and were more likely to be anephric (P less than 0.001) and to have a history of prior renal transplantation (P less than 0.10). The 12 patients with significant bone iron staining had received more blood transfusions than those without bone iron staining (96 +/- 22.8 U v 22 +/- 5.8 U, P less than 0.005). Patients with bone iron accumulation had higher levels of serum ferritin (3,594 +/- 1,138.4 micrograms/L [ng/mL] v 265 +/- 60.1 micrograms/L, P less than 0.01) and lower levels of immunoreactive parathyroid hormone (iPTH) (349 +/- 150 microLEq/mL v 1,801 +/- 397 microLEq/mL [386 +/- 166 pmol/L v 1,990 +/- 439 pmol/L], P less than 0.005). BIC was also higher in these patients (1,008 +/- 149 micrograms iron/g bone v 300 +/- 46.5 micrograms iron/g bone, P less than 0.001) and higher than normal BIC (256 +/- 44.2 micrograms iron/g bone, eight normals). Bone marrow iron stores were positively related to serum ferritin levels (P less than 0.01) and trabecular bone iron staining (P less than 0.10). All 13 patients with osteomalacia demonstrated significant bone aluminum staining; seven of these patients demonstrated concomitant significant iron staining. Fourteen of 15 patients with severe hyperparathyroidism showed no significant iron or aluminum staining. Our data indicate that iron will probably not accumulate within bone until all other storage sites (eg, bone marrow) are fully saturated. The presence of lower levels of iPTH in iron-overloaded patients raises the possibility that iron overload may induce a state of relative hypoparathyroidism. The most important determinant for the presence of osteomalacia seems to be the presence of significant aluminum staining. No specific bone histologic finding was related to the presence of bone iron staining, but the rarity of isolated significant bone iron staining makes it difficult to evaluate bone histologic diagnoses that might be solely attributable to iron.
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We have investigated the importance of several clinical and laboratory parameters on the development of acquired cystic kidney disease (ACKD) as detected by ultrasonography in 19 patients who had received dialysis therapy for at least three years. We were particularly interested on the possible effect of the serum levels of oxalate and silicon, which can produce tubular obstruction, and that of vanadium, which can affect cell proliferation. The severity of ACKD increased with the duration of dialysis and was greater in men than in women. Positive correlations were observed between the grades of ACKD and the levels of hemoglobin, hematocrit, and parathyroid hormone, while there was a negative correlation between ACKD and serum ferritin levels. The serum levels of oxalate, silicon, and vanadium, pre- and postdialysis, were markedly and significantly higher than those in normal controls, but there was no significant correlation between these levels and the duration of dialysis therapy or severity of ACKD. The pre- and postdialysis levels of vanadium were not significantly different, while the levels of oxalate and silicon were significantly lower in the postdialysis samples. No significant correlations were detected between ACKD and age of the patients, blood pressure, protein catabolic rate, efficiency of dialysis index, or the serum levels of iron, sodium, potassium, calcium, phosphorus, aluminum, and beta 2-microglobulin.
We report a case of ciprofloxacin-related allergic tubulointerstitial nephritis, which manifested as nonoliguric renal failure, eosinophilia, and eosinophiluria. Our patient responded to discontinuation of ciprofloxacin therapy and oral administration of a brief course of corticosteroids. Although rare, allergic tubulointerstitial nephritis apparently can be caused by ciprofloxacin therapy. Clinicians should be aware of this entity.
Seizures, hypertensive encephalopathy, transient ischemic attacks, and thrombosis of hemodialysis accesses occurred in early clinical trials with recombinant human erythropoietin. To determine if these events may be caused by the increased hematocrit value or some direct effect of the recombinant human hormone, 10 transfusion-dependent hemodialysis patients were divided into two groups of five according to their serum ferritin concentration: group A. less than 800 microgram/liter, and group B. greater than 800 micrograms/liter. After a month of placebo administration, recombinant human erythropoietin was given (150 U/kg intravenously thrice weekly) for four months and then stopped for one month. Hematocrit values were maintained at 0.33 +/- 0.02 (mean +/- SD) by dose adjustment in group A and at 0.26 +/- 0.02 by thrice weekly phlebotomies in group B, who received a constant dose of erythropoietin. Viscosity increased from subnormal to normal in group A (P less than 0.02) and cerebral blood flow decreased from above normal to normal (P less than 0.02). In group B minor, statistically insignificant, changes in viscosity and reciprocal changes in cerebral blood flow also occurred. There was no change in either group in transcutaneous oxygen tension. Bleeding time decreased toward normal in both groups during recombinant human erythropoietin administration but the changes did not reach statistical significance. Fibrinogen levels were increased in all patients but remained unchanged. No other significant coagulation-related changes were observed. Recombinant erythropoietin in the dosage and schedule of administration described in this study did not lead directly or indirectly to changes likely to precipitate seizures or intravascular thrombosis.
A desferrioxamine (DFO) infusion test, using a DFO dose of 36.9 +/- 11.2 mg/kg (mean +/- SD), was performed in 50 consecutive dialysis patients undergoing diagnostic bone biopsy. In 30 patients whose bones stained positively for aluminium the serum aluminium level increased by an average of 373 +/- 250.4 ng/ml. The increase in 20 aluminium-negative patients was 231 +/- 179.2 ng/ml (p less than 0.05). Aluminium-positive patients had lower levels of immunoreactive parathyroid hormone (336 +/- 442 muleq/ml) than aluminium-negative patients (1278 +/- 1400 muleq/ml; p less than 0.05). A change in serum aluminium level of greater than 200 ng/ml after the administration of DFO was 73 percent sensitive and 50 percent specific, and had a positive predictive value of 69 percent for detecting positive bone aluminium staining. The combination of a baseline immunoreactive parathyroid hormone level less than 200 muleq/ml and a change in serum aluminium of greater than 200 ng/ml after DFO was 90 percent specific and had a positive predictive value of 85 percent. In the second phase of our study, 28 dialysis patients with aluminium toxicity received long-term therapy (11.0 +/- 4.3 months) with DFO at an average starting dose of 41.7 +/- 17.1 mg/kg, administered once weekly. The four deaths which occurred during this treatment involved the only patients who had advanced dialysis dementia. Seven patients with less severe neurological symptoms responded favourably. Fractures decreased from 1.7 fractures/patient/year to 0.1 fracture/patient/year. Muscular strength and overall functional class were improved or stable in 25 patients; myalgias and arthralgias were also stable or improved in 19 patients. After 5-7 months of treatment, serum aluminium levels decreased from 401 +/- 262 ng/ml to 245 +/- 217 ng/ml (p less than 0.01); erythrocyte mean corpuscular volume increased from 86.3 +/- 10.91 fl to 94.1 +/- 9.23 fl (p less than 0.02); and serum calcium decreased from 10.4 +/- 0.94 mg/dl to 9.9 +/- 0.70 mg/dl (p less than 0.02). Serum immunoreactive parathyroid hormone levels remained stable in 25 patients, but severe hyperparathyroidism developed rapidly in three patients. Eight patients with transfusional iron overload had no change in serum ferritin levels. Iron depletion developed in six patients, with a decrease in serum ferritin from 251 +/- 229.8 micrograms/l to 45 +/- 29.3 micrograms/l, and they required parenteral iron supplementation. Significant side-effects occurring during long-term DFO administration were hypotension (11 patients), gastrointestinal upset (seven patients), porphyria cutaneous tarda-like lesions (three patients), and transient visual disturbance (one patient). There was a decrease in stainable bone aluminium in all nine patients with paired bone biopsy specimens (pre- and post-DFO).(ABSTRACT TRUNCATED AT 400 WORDS)
Renal osteodystrophy is a complex disorder which can be divided into five distinct bone histologic subtypes: mild bone disease, hyperparathyroid bone disease, mixed bone disease, osteomalacia, and low-turnover bone disease. Hyperparathyroidism develops in renal failure due to two principal abnormalities: 1,25(OH)2D3 deficiency and hyperphosphatemia. Treatment of these problems is important in order to prevent hyperparathyroidism. Most cases of osteomalacia, mixed bone disease, and low-turnover bone disease are influenced by aluminum status and parathyroid hormone. Aluminum-associated bone disease can be treated with termination of aluminum exposure and/or deferoxamine therapy. Numerous diagnostic pitfalls exist in the evaluation of renal osteodystrophy, and the bone biopsy is extremely important to avoid these problems and plan proper therapy.