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Biomedical subjects

R S Muther

Publications and source records attributed to R S Muther.

At least 19 recordsLinked to original sources

Assessing university nephrology training as preparation for community consultative practice.

The authors gathered information about the consultative practice of nephrology in a community environment and used this information to speculate about improvements that could be made in the training of nephrologists in academic medical centers, based on their knowledge of such training. Data were gathered on the specialty affiliations of the physicians who requested 211 consecutive consultations, on the clinical problems encountered, and on the most likely diagnosis for each problem. In some instances the referral patterns, patient mixes, and clinical diagnoses observed in the community-based practice differed significantly from those often emphasized in training programs in academic medical centers. Such differences may be unintentionally reinforced, because the clinical literature in which new findings are reported and validated largely arises from university-type clinical practices. Specific examples of the differences observed and some suggestions for change are given. Although additional research is needed to confirm the findings of this study, and although these findings may not be applicable to other settings or other internal medicine subspecialties, these findings raise questions about the appropriateness of completely university-based training in preparing physicians for practice in a community setting. The authors suggest that cooperation between community hospitals and established university programs could bring about the best opportunities for clinical training.

Community Medicine

Nitroprusside-induced acute azotemia.

A patient with congestive heart failure and pneumonia was begun on a nitroprusside infusion for cardiac afterload reduction. Urine output declined sharply and azotemia ensued despite little change in arterial pressure. Further evaluation supported a prerenal mechanism with dramatic recovery related to tapering and discontinuation of the nitroprusside. The mechanism of renal deterioration is possibly related to a 'steal' syndrome due to preferential dilation of vascular beds other than the renal.

Acute Kidney Injury

Parathyroid function in persistent hyperparathyroidism: relationship to gland size.

The release of parathyroid hormone in experimental animals is related inversely to the plasma calcium concentration. The relevance, though, of these observations to the dynamics of parathyroid function in normal and hyperparathyroid humans is uncertain. We assessed the in vivo parathyroid hormone response to changes in extracellular calcium in 8 normal subjects and 15 patients with persistent hyperparathyroidism following renal transplantation. In 12 hyperparathyroid patients, the hormone response was related to their total gland size measured at the time of their parathyroidectomy. Plasma ionized calcium, magnesium, and parathyroid hormone concentrations were measured in the basal state and during a 2-hr infusion of EDTA (50 mg/kg), and a 4-hr calcium infusion (15 mg/kg). The parathyroid function curves of both groups of subjects (P less than 0.001) fit a log-linear relationship. The slopes of the respective parathyroid function curves were similar, although the hyperparathyroid curve was shifted to the right (P less than 0.0001). Gland size was not predicted by basal PTH levels; however, it did correlate with changes in parathyroid hormone induced by EDTA (P less than 0.001) and calcium (P less than 0.001). We conclude that the in vivo sensitivity of hyperplastic glands to changes in plasma calcium is maintained. The excessive secretion of immunoreactive parathyroid hormone in chief cell hyperplasia primarily reflects total gland mass. Our results indicate that the assessment of the dynamics of parathyroid response, rather than measurements of static plasma parathyroid hormone and calcium concentrations, should be further investigated as a more rational application of radioimmunoassays in the evaluation of the parathyroid axis.

Adult

Change in serum bicarbonate during acute EDTA infusions in post-transplant hyperparathyroidism.

We evaluated the effect of endogenous parathyroid hormone (PTH) on serum bicarbonate in 12 patients with postrenal transplant hyperparathyroidism. EDTA-induced hypocalcemia produced a significant rise in serum PTH (p less than 0.001). Associated with the increase in PTH was a significant fall in plasma bicarbonate (p less than 0.001) and increase in the chloride: phosphorus ratio (p less than 0.001). Magnesium remained stable but serum potassium fell in response to EDTA. These observations suggest that endogenous PTH can significantly affect plasma bicarbonate in vivo and may contribute to post renal transplant renal tubular acidosis.

Bicarbonates

Ionized calcium and the in vivo response of normal and hyperplastic parathyroid glands to beta-adrenergic agents.

We compared ionized serum calcium and parathyroid hormone (PTH) responses to the beta-adrenergic agents, isoproterenol and propranolol, in 14 patients with hyperparathyroidism following renal transplantation and 8 normal volunteers. Following isoproterenol, PTH rose in normal subjects concurrent with a significant (p less than 0.01) fall in ionized but not total, calcium. In the hyperparathyroid patients the PTH concentration decreased (p less than 0.001) coincident with a significant (p less than 0.01) increase in ionized, but not total, calcium. Changes in both PTH (p less than 0.05) and ionized calcium (p less than 0.05) were significantly different in hyperparathyroid patients compared to normal subjects. Propranolol did not affect PTH, ionized or total calcium in either group. We conclude that beta-adrenergic stimulation of PTH secretion may be mediated, in part, by antecedent changes in ionized calcium and not solely a direct effect of the agonist. Concurrent assessment of changes in ionized calcium is necessary for proper interpretation of investigations involving the sympathetic nervous system's regulation of PTH secretion.

Adult

Parathyroid hormone: a determinant of posttransplant blood pressure regulation.

Persistent hyperparathyroidism and its attendant hypercalcemia have been implicates as possible etiologic factors in posttransplant hypertension. To better define the role of parathyroid hormone (PTH) and calcium in posttransplant blood pressure homeostasis, we measured the acute response of blood pressure, ionized calcium (Ca++), plasma renin activity (PRA), and parathyroid hormone (PTH) to a 4-hr infusion of calcium (15 mg/kg) and an isoproterenol injection (0.15 mg SC) in seven normal subjects and 13 renal transplant (Tx) recipients with stable graft function and persistent hyperparathyroidism. Transient hypercalcemia produced a significant (p less than 0.01) increase in the systolic blood pressure (delta SBP) and suppression of PTH (p less than 0.001) in the posttransplant subjects. There was a significant (p less than 0.02) inverse correlation between changes (delta) in PTH and delta SBP in these subjects. There was no correlation between the delta SBP and either the change in Ca++ (delta Ca++) or the change in PRA (delta PRA) observed in the Tx recipients administered calcium. Following isoproterenol administration, SBP increased (p less than 0.01), PTH fell (p less than 0.05) and Ca++ was only minimally increased in the Tx recipients. A virtually identical, significant (p less than 0.05) inverse correlation existed between the delta PTH and delta SBP observed in the transplant subjects. Greater suppression of PTH was associated with a larger increase in systolic blood pressure. Transient hypercalcemia of comparable degree in normal subjects caused an insignificant increase in their blood pressure. The fact that PTH suppression in the normals was substantially (0.01) less (delta PTH -13 microliter/Eq/ml versus -65 microliter/Eq/ml in the transplant group) with a similar increase in serum calcium suggests that the blood pressure response to transient hypercalcemia is more dependent on PTH suppression than the level of ionized calcium. Plasma renin activity was unchanged during the blood pressure fluctuations induced by either the calcium or the isoproterenol administration to the normal subjects. Under the conditions of this study, endogenous parathyroid hormone has the characteristics of a vasodepressor hormone and may have a role in blood pressure regulation in transplant recipients with hyperparathyroidism. Since the vasodepressor effect can be dissociated from delta Ca+ and delta PRA, such a conclusion seems warranted. The implications of these findings for all subjects with renal disease requires further investigation.

Blood Pressure

Cyst fluid antibiotic concentrations in polycystic kidney disease: differences between proximal and distal cysts.

The concentrations of several antibiotics were measured in the cyst fluid of six adult patients with polycystic kidney disease. Seventy-nine cysts were aspirated at surgery or autopsy. Sixty-one cysts could be categorized as arising from the proximal nephron and 16 from the distal nephron by cyst fluid to serum sodium ratios. Serum, urine, and cyst fluid were simultaneously analyzed for sodium, creatinine, and various antibiotics. Gentamicin, tobramycin, cephapirin, and ticarcillin were either undetectable or present in low concentrations in renal cysts. Cyst fluid antibiotic concentrations did not correlate with cyst volume or creatinine clearance. Cysts of proximal nephron origin had higher antibiotic concentrations than distal cysts. In one patient with normal renal function, inulin was undetectable in renal cysts after a continuous 36-hour i.v. infusion. Para-aminohippurate, however, was detected in the renal cysts of this patient. These data help explain the poor clinical response of infected renal cysts to antibiotic therapy. They also suggest that antibiotics and other solutes may enter cyst fluid across tubular cells in addition to entry by glomerular filtration.

Anti-Bacterial Agents

Lack of nephrotoxicity of intravenous dimethylsulfoxide.

Intravenous dimethylsulfoxide (DMSO) was used to treat seven patients with stable spinal cord injuries. Because of drug-associated hemoglobinemia and hemoglobinuria, the patients were studied for subtle evidence of renal tubular dysfunction by serial measurements of urinary beta-2-microglobulin excretion. No increases in tubular protein excretion or decreases in glomerular filtration rate were observed following short-term infusions of 10-40% DMSO. It is concluded that there is no significant short-term nephrotoxicity from intravenous DMSO.

Adolescent

Aspirin-induced depression of glomerular filtration rate in normal humans: role of sodium balance.

The renal clearance of endogenous creatinine, inulin and para-aminohippurate was measured in 10 healthy human volunteers taking aspirin during severe dietary sodium restriction (10 meq/d) to clarify the clinical significance and pathophysiology of aspirin-induced changes in renal function. Sodium restriction alone had no effect on renal clearances but did increase plasma renin activity and urinary prostaglandin E excretion. The addition of aspirin decreased the urinary clearance of prostaglandin E but not plasma renin activity, and caused a significant fall in both endogenous creatinine (from 92.3 +/- 4.1 SE ml/min . 1.73 m2 body surface area to 80.8 +/- 4.4 mL/min . 1.73 m2, p = 0.02) and inulin (from 95.3 +/- 7.0 mL/min . 1.73 m2 to 80.9 +/- 7.0 mL/min . 1.73 m2, p less than 0.001). The fall in inulin clearance was directly related to the salicylate level. The clearance of para-aminohippurate showed only a slight, statistically insignificant decline with aspirin. The results of this study suggest that aspirin-induced depression of glomerular filtration rate may be independent of total renal plasma flow. Aspirin should be used cautiously, with careful attention to dosage, in sodium-restricted patients whose glomerular filtration rate may, in part, be under the homeostatic control of renal prostaglandins.

Adult

Renal manifestations of sarcoidosis.

Sarcoidosis may involve the kidneys in several ways. Most commonly, aberrations of calcium metabolism, including hypercalcemia, hypercalciuria, and nephrocalcinosis, are responsible for the renal manifestations of sarcoidosis. Granulomatous infiltration of the renal interstitium may also produce severe derangements of renal function. Glomerulonephritis can occur with sarcoidosis, although the pathogenesis remains unclear. Besides renal insufficiency and frank renal failure, nephrotic syndrome, nephrolithiasis, hypertension, and a variety of tubular defects may complicate sarcoidosis. The sensitivity of "sarcoid nephropathy" to corticosteroids usually warrants therapeutic trial.

Glomerulonephritis

Effects of dimethyl sulfoxide on renal function in man.

To ascertain the clinical significance of dimethyl sulfoxide-induced pigmenturia, we evaluated renal function and indicators of systemic hemolysis in stable quadriplegic patients receiving the drug intravenously (IV) for spinal cord injury. Despite a dose-dependent transient hemolysis with resultant hemoglobinuria, no alteration of renal function could be appreciated. Other than the presence of urinary hemoglobin, there were no changes from baseline in the urinary sediment and all patients remained without severe hematuria. Our results indicate that patients treated with IV dimethyl sulfoxide for severe cerebral edema could serve as donors for renal transplantation.

Adolescent

Percutaneous aspiration biopsy of renal allografts using ultrasound localization.

Percutaneous aspiration of renal allografts was done employing ultrasound localization and the Jamshidi renal biopsy needle-syringe. Adequate tissue for pathologic assessment was obtained in 19 of 20 biopsy attempts. There were no complications. Ultrasound provides a convenient, nonradiologic means of renal localization for allograft biopsy. The aspiration needle-syringe is well suited for percutaneous transplant biopsy.

Biopsy, Needle

Concentration of antibiotics in simple renal cysts.

Patients with infected renal cysts are known to respond poorly to antibiotic therapy. We evaluated the serum, cyst fluid and urine levels of 3 antibiotics in 4 patients with simple renal cysts. Despite excellent urine and serum concentrations gentamicin was detected in the cyst of only 1 of the 3 patients studied. Neither sulfamethoxazole nor trimethoprim was detected in the cyst of 1 patient despite adequate plasma levels. These data help explain the poor medical response of such patients and support the concept of early surgical intervention.

Anti-Bacterial Agents