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Biomedical subjects

D T Domoto

Publications and source records attributed to D T Domoto.

At least 19 recordsLinked to original sources

A randomized trial of sevelamer hydrochloride (RenaGel) with and without supplemental calcium. Strategies for the control of hyperphosphatemia and hyperparathyroidism in hemodialysis patients.

OBJECTIVE: We have previously shown sevelamer hydrochloride (RenaGel) to be an effective and well-tolerated treatment for hyperphosphatemia in hemodialysis patients. PATIENTS AND METHODS: We performed a randomized clinical trial to compare the efficacy of RenaGel alone and RenaGel with calcium, using the serum phosphorus concentration and intact parathyroid hormone (PTH) as the principal outcomes of interest. Calcium (900 mg elemental) was provided as a once-nightly dose on an empty stomach. 71 patients were randomized and included in the intent-to-treat population; 55 completed the 16-week study period (2 weeks washout, 12 weeks treatment, 2 weeks washout). 49% of subjects were taking vitamin D metabolites. RESULTS: Serum phosphorus and PTH rose significantly when patients stopped their phosphate binders during both washout periods. RenaGel and RenaGel with calcium were equally effective at reducing serum phosphorus (mean change -2.4 mg/dL vs. -2.3 mg/dL). RenaGel with calcium was associated with a small increase in serum calcium (mean change 0.3 mg/dL vs. 0.0 mg/dL in RenaGel group, P = 0.09) that was not statistically significant. During the treatment phase, the reduction in PTH tended to be greater in the RenaGel with calcium group (median change -67.0 vs. -22.5 pg/mL in RenaGel group, P = 0.07). Non-users of vitamin D metabolites treated with RenaGel with calcium experienced a significant decrease in PTH (median change -114.5 vs. -22 pg/mL in RenaGel group, P = 0.006). Adverse events were seen with equal frequency in both groups, being generally mild in intensity, and rarely attributable to the drugs. CONCLUSION: We conclude that RenaGel and RenaGel with calcium are similarly effective in the treatment of ESRD-related hyperphosphatemia. Provision of supplemental calcium or metabolites of vitamin D with RenaGel may enhance control of hyperparathyroidism.

Calcium↗

Bioimpedance analysis of fluid compartments in female CAPD patients.

Dry weight is difficult to determine in continuous ambulatory peritoneal dialysis (CAPD) patients. Bioimpedance spectroscopy using a multi-frequency analyzer was used to measure total body water, extracellular water, and intracellular water in 7 female CAPD patients and, for comparison, in 6 normal female controls. One patient was measured a second time after a 10-kg fluid loss. Mean weight in controls and CAPD patients was similar, as was the percent of body weight that was water. However, the ratio of extracellular water to intracellular water was 0.814 in controls but 1.11 in CAPD patients, suggesting either more extracellular water and/or less intracellular water in the CAPD patients compared to the controls. When analyzed, the percent of total body water that was extracellular was significantly greater in the CAPD group. There was also a significant reduction in the percent of intracellular water that contributed to body weight in the CAPD patients. Body cell mass was 38.1% in controls but only 30.2% in CAPD patients. Serum albumin concentration ranged from 2.1 to 4.2 g/dL in CAPD and a linear relationship was present between serum albumin concentration and cell membrane capacitance. We conclude that 60% of body weight as body water may be an overestimate of volume (V) when the formula Kt/V is used to measure adequacy, and that bioimpedance spectroscopy may be a useful technique for assessing both fluid balance and body cell mass or nutritional status in CAPD patients.

Adult↗

Henoch-Schoenlein purpura due to streptokinase.

The syndrome of Henoch-Schoenlein purpura developed in a 74-year-old woman after receiving streptokinase as thrombolytic therapy for an acute myocardial infarction. Renal biopsy revealed mesangial hypercellularity with deposits of IgA. Skin biopsy also revealed IgA deposition. Immunological studies showed evidence of sensitization to streptokinase. Elevated IgG, IgA, IgM, and IgE antistreptokinase antibodies were detected in the acute serum. Positive immediate skin reactivity to streptokinase was also present. Serum precipitins to streptokinase disappeared when IgA was removed from the serum. Positive staining with biotinylated streptokinase was seen in the skin in the same pattern of distribution as IgA. These findings strongly support the role of streptokinase and IgA in the pathogenesis of Henoch-Schoenlein purpura in this patient. A control group of streptococcal-infected patients showed no immune response to streptokinase. Another control group of streptokinase-treated patients, who had no untoward reaction, had elevated immunoglobulin classes and precipitins to streptokinase. However, the precipitating antibody was IgG and streptokinase skin tests were negative.

Aged↗

Pulse oral calcitriol for the treatment of hyperparathyroidism in patients on continuous ambulatory peritoneal dialysis: preliminary observations.

A direct effect of calcitriol on the regulation of the secretion of parathyroid hormone (PTH) has been shown in vitro and in vivo. In patients with renal failure on maintenance hemodialysis, it has been shown that intravenous (IV) administration of calcitriol appears to be superior to continuous oral administration. This may be due to the higher levels of calcitriol obtained in blood with consequent improved delivery of calcitriol to peripheral target tissues including the parathyroid glands. However, IV administration of calcitriol, is not practical for patients with end-stage renal disease (ESRD) who are maintained on continuous ambulatory peritoneal dialysis (CAPD). The present studies were designed to investigate whether intermittent administration of large doses of calcitriol orally ("pulse therapy") could mimic the effects of IV calcitriol in hemodialysis patients and achieve suppression of PTH secretion. Studies were performed in five patients who had been maintained on CAPD for more than 6 months. After basal determinations of calcium, phosphorus, and PTH, therapy was begun with calcitriol administered orally in a dose of 5 micrograms given twice per week. Calcium carbonate was continued as a phosphate binder. Dialysate calcium concentration was 1.75 mmol/L (3.5 mEq/L). With this therapy, PTH levels decreased rapidly, and, after 4 to 6 weeks of therapy, reached values 60% lower than pretreatment values. Mean values for serum calcium did not change significantly (2.29 +/- 0.12 mmol/L [9.6 +/- 0.5 mg/dL] before treatment compared with 2.32 +/- 0.08 mmol/L [9.7 +/- 0.25 mg/dL] after therapy). Mean serum phosphorus was also unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Failure of CAPD patients to respond to an oral iron absorption test.

CAPD patients require supplemental iron to maintain a response to erythropoietin. Because of limited availability of parenteral iron dextran, oral iron must be used. However, oral iron may not be effective in most dialysis patients. To determine if oral iron is well absorbed, a modified oral iron absorption or tolerance test was performed in CAPD patients using two oral iron preparations. Serum irons were measured at baseline in a fasting state and repeated two hours after the ingestion of 325 mgs ferrous sulfate in five CAPD patients. In addition, eight patients had serum irons determined before and two hours after taking liquid oral ferrous fumarate in capsule form. Healthy controls were compared with each group. All five patients who received ferrous sulfate had borderline to low normal serum iron and iron stores. Average increase in serum irons was only 19 mcg/dl in patients compared to 52 mcg/dl in controls. Patients receiving ferrous fumarate rose only 14 mcg/dl compared to 60 mcg/dl in controls. We conclude that oral iron is poorly absorbed in most CAPD patients and that the oral iron absorption test may be helpful in identifying patients who are effective iron absorbers. Unfortunately, until parenteral iron dextran is readily available, oral iron therapy is the only alternative for iron supplement. The oral iron absorption test may predict who will respond to oral iron in the long-term.

Administration, Oral↗

Combined aspirin and sulfinpyrazone in the prevention of recurrent hemodialysis vascular access thrombosis.

We carried out a pilot study in 15 hemodialysis patients with recurrent vascular access thrombosis to examine whether the combination of low dose aspirin (85 mg once daily) and sulfinpyrazone (200 mg three times daily) is safe and effective in the prevention of vascular access thrombosis. Hemostatic measurements were performed prior to and after four weeks of starting the drug combination. Baseline values for fibrinopeptide A were elevated in all patients while those for platelet factor 4, fibrinogen, antithrombin III and protein C were generally within normal limits. A major reduction in the frequency of vascular access thrombosis from 0.114 per month to 0.04 per month was noted during combined drug treatment (p less than 0.001). Although in vitro platelet aggregation to various stimuli was markedly suppressed and platelet thromboxane B2 formation was almost completely inhibited in patients on aspirin/sulfinpyrazone, this was not associated with a significant further prolongation of the bleeding time. A relatively high rate of complications, particularly mild gastrointestinal bleeding, was noted in patients on aspirin/sulfinpyrazone that could not be predicted on the basis of pre-treatment hemostatic test results.

Aspirin↗

Androgens potentiate the effects of erythropoietin in the treatment of anemia of end-stage renal disease.

Since androgens may increase the sensitivity of the erythroid progenitors to erythropoietin, the present studies were designed to investigate the effect of administration of androgens on the actions of exogenous erythropoietin (EPO) in hemodialysis patients. Studies were performed in a group of 15 adult male hemodialysis patients. Seven patients were treated with EPO alone at a dose of 2,000 U intravenously (IV) three times a week. An additional group of eight patients was treated with 2,000 U of EPO three times a week and also received 100 mg of nandrolone decanoate intramuscularly (IM) each week. After 12 weeks of therapy, hematocrit values increased slightly in the group receiving EPO alone, from 25.3 +/- 0.8 to 27.4 +/- 1.5. In contrast, EPO in combination with nandrolone decanoate resulted in a greater increase in hematocrit values, from 24.4 +/- 1.4 to 32.9 +/- 1.8 (P less than 0.001). The results show that the groups receiving low-dose EPO alone had a poor erythropoietic response. In contrast, patients receiving androgen in addition to EPO had a significantly greater increase in hematocrit values with treatment. Transfusions were eliminated in both groups of patients. These data show that androgen therapy significantly augments the action of exogenous EPO such that lower doses of EPO are sufficient for an adequate hematopoietic response.

Anabolic Agents↗

Characterization of eosinophils in a continuous ambulatory peritoneal dialysis patient with eosinophilic peritonitis.

A continuous ambulatory peritoneal dialysis patient developed eosinophilic peritonitis and was followed for 7 months. After 1 month, the peritonitis resolved, with a concomitant drop in percentage of hypodense eosinophils (Eos) recovered from peritoneal dialysate (PD) as well as a drop in fluid major basic protein levels. Blood eosinophil differential percentages were low, but the percentage of hypodense Eos in the blood tended to be relatively increased. Stool samples showed no evidence of parasitic infection, and epicutaneous skin tests were negative. Leukotriene C4 levels remained relatively constant as did white blood cell counts. Flow cytometric analysis of lymphocytes and granulocytes from PD and blood revealed high levels of CD23-positive lymphocytes.

Adult↗

Efficacy of streptokinase in resistant, relapsing or recurrent CAPD peritonitis.

The efficacy of streptokinase to lyse biofilm in the catheters of CAPD patients with peritonitis was examined in a retrospective review of 10 infusions in 9 patients with difficult to resolve peritonitis. 750,000 units of streptokinase were used. This helped resolve peritonitis in 8 of 10 uses, including two cases due to gram negative bacteria. Staphylococcus was cultured in the other 8 cases. The two episodes which failed to respond were due to Staph epidermidis relapsing peritonitis and required either catheter removal or two additional courses of antibiotics before peritonitis resolved. One infusion was complicated by severe hypotension which was thought to be due to generalized sepsis. The patient had received a previous streptokinase infusion but skin tests for IgE allergy to streptokinase were negative. We conclude that streptokinase is efficacious in the resolution of slow to resolve peritonitis due to either gram positive or gram negative organisms, and potentially saved seven patients from catheter removal.

Adult↗

Recurrent peritonitis need not be a cause of CAPD dropout.

Though excessive peritonitis is reported as the cause of 27% of CAPD dropout, over a five-year period, only 5 of 41 patients (12%) who had 5 or more episodes of peritonitis stopped CAPD because of excessive peritonitis. Their average time on CAPD prior to stopping was significantly longer than other dropouts with less peritonitis. Only one patient technically could not continue PD. We conclude that excessive peritonitis need not be a major cause for CAPD dropout.

Humans↗

Continuous cyclic peritoneal dialysis--is it worth the extra effort?

Despite theoretical advantages of CCPD, only 1 of 13 patients trained in this modality continue on CCPD in a 3 year review period. Average duration on CCPD was only 7 months. When compared with our CAPD population higher transplant rates, death rates, and dissatisfaction with the dialysis technique, but not higher peritonitis rates were reasons for terminating CCPD.

Adult↗

Removal of toxic levels of N-acetylprocainamide with continuous arteriovenous hemofiltration or continuous arteriovenous hemodiafiltration.

Two patients with renal failure developed N-acetylprocainamide toxicity while receiving procainamide. Treatment consisted of continuous arteriovenous hemofiltration in one and hemodialysis followed by continuous arteriovenous hemodiafiltration in the other. The efficacy of these treatments was compared with the efficacy of three-times-weekly hemodialysis as used in two patients on chronic hemodialysis who had elevated N-acetylprocainamide levels. Continuous methods produced a more rapid reduction in N-acetylprocainamide levels than intermittent hemodialysis.

Acecainide↗

Antibiotic treatment of chronic central venous hemodialysis catheter infection without catheter removal.

Most catheter or shunt infections in hemodialysis patients require the removal of the access before the infection is eradicated. A hemodialysis patient is reported who had multiple previous vascular accesses which failed and thus who had very limited sites for future access placement. When a recurrent Proteus mirabilis catheter infection occurred, a 6-week course of ampicillin intraluminal and tobramycin systematically, eradicated the infection and thus the central venous catheter was salvaged. Serum bactericidal levels with these two antibiotics were obtained early in the course and supported the continued use of antibiotics alone to treat the infection.

Ampicillin↗

Aging and the kidney.

Numerous anatomic and physiologic alterations occur in the kidney with aging. These changes affect the ability of elderly patient(s) to maintain homeostasis and alter response to medications, stress, illness, or changes in diet, mobility, or environment. Drug-induced illness and drug interactions are major problems in the elderly. Bone disease and fractures are associated with negative calcium balance and decreased production of 1,25-dihydroxycholecalciferol seen with aging. The geriatric patient is not immune to the primary glomerular diseases that occur in younger patients, although the relative incidence of pathologic diagnoses may differ. The high incidence of membranous glomerulonephritis in the elderly, and the well-known association between malignancy and membranous nephropathy strongly favor aggressive evaluation of the nephrotic syndrome in the geriatric age group. Attention must be given to consideration of appropriate end-stage renal disease treatment alternatives for the geriatric population, which now comprises the fastest-growing segment of the end-stage renal disease population.

Adult↗

Two years clinical experience with continuous arteriovenous hemofiltration in acute renal failure.

Clotting of hemofilters is the most frequent single cause of filter failure. These filters frequently clot in spite of acceptable hemodynamic and anticoagulation parameters. Sixty percent of filters which eventually clotted never filtered above 200 ml/hr. In our experience maximum ultrafiltration rates of 500 ml/hr to over 1000 ml/hr are rarely achieved in routine clinical usage. Finally, a disproportionate number of filters accessed to the lower leg either clotted or were discontinued for subsequent dialysis. Thus, we conclude that lower leg accesses should be avoided if possible. Further, to prevent clotting, in addition to maintaining adequate anticoagulation and cardiac output, maximum ultrafiltration rates should be sought. To achieve maximum ultrafiltration rates, a good vascular access is primary. Also, a vacuum system may be needed and perhaps routinely used to obtain filtration rates near 500 ml/hr. These high filtration rates will also reduce the need for hemodialysis, the second most common reason for filter discontinuation.

Acute Kidney Injury↗

H-2-dependent cell-mediated immunity in vivo: delayed-type hypersensitivity and contact sensitization induced by fluorescein isothiocyanate-conjugated cells.

Fluorescein isothiocyanate (FITC) was found to be a suitable hapten to study cell-mediated immunity in vivo in mice. Delayed-type hypersensitivity (DTH) footpad swelling reactions were induced and elicited by injection of FITC-conjugated syngeneic spleen cells, and contact sensitivity (CS) was induced and elicited by skin painting with reactive FITC. Cross-reactive specificity between DTH and CS was demonstrated. Thus, DTH induction with FITC-spleen cells (FITC-SC) also led to the ability to elicit CS; and CS induction by skin painting also led to the ability to elicit DTH with FITC-SC. However, the 2 reactions differed in that the ability to elicit DTH induced by subcutaneous immunization with FITC-SC was evanescent, whereas CS induced by skin painting was long lived. Specificity of these reactions was hapten dependent and additionally required homology at the H-2 locus of the major histocompatibility complex. The H-2 specificity requirement was not evanescent.

Animals↗