Alan J. Watson

Syndrome of Idiopathic Hyperammonemia after High-Dose Chemotherapy: Review of Nine Cases

PURPOSE The syndrome of idiopathic hyperammonemia occurs in patients who have received high-dose cytoreductive therapy for the treatment of hematologic malignancy. It is characterized by abrupt alteration in mental status and respiratory alkalosis associated with markedly elevated plasma ammonium levels in the absence of any identifiable cause, and frequently results in intractable coma and death. Our goal was to survey clinical and pathologic manifestations of the disorder and discuss treatment options. PATIENTS AND METHODS Plasma ammonium levels were measured in patients on the acute leukemia service or on the bone marrow transplant service at The Johns Hopkins Hospital, and a level more than twice normal was considered diagnostic of hyperammonemia. The syndrome was identified in nine patients; in eight, hyperammonemia occurred after administration of intensive cytoreductive therapy that resulted in profound leukopenia. The disorder occurred in the ninth patient two months after allogeneic bone marrow transplantation. RESULTS Three of the nine patients survived an episode of idiopathic hyperammonemia; one patient subsequently died of leukemia and one of recurrent idiopathic hyperammonemia. The one long-term survivor is currently alive and well without neurologic sequelae 250 days after autologous bone marrow transplantation. CONCLUSION Because neurologic function can deteriorate rapidly, early recognition of this disorder and close monitoring of the patients neurologic status are critical.

Domestic Cases of Hemorrhagic Fever with Renal Syndrome in the United States

Although serologic studies have identified hantaviral infection in the United States, acute disease has not been recognized. This study describes 3 cases of domestically acquired hemorrhagic fever with renal syndrome (HFRS) in the United States. Infection was due to a local strain of Seoul virus (Baltimore rat virus). A review of the clinical features indicated a mild illness characterized by nausea, vomiting, renal and liver failure similar to HFRS described elsewhere for rat-borne viruses. Follow-up of 2 patients identified persistent hypertension and renal disease providing further evidence of an association between past hantaviral infection and hypertensive renal disease.

Screening for Dialysis Access Graft Malfunction: Comparison of Physical Examination with US

PURPOSE To test the reliability and performance of two physical diagnosis algorithms for use in physical examination of vascular access grafts. MATERIALS AND METHODS Grafts were assessed in 39 patients by means of physical examination performed by four observers. Grafts were characterized as having a thrill, pulse, or indeterminate examination at three locations (arterial, midpoint, venous). Findings with this algorithm were compared with those from ultrasound (US) with volume flow measurements. RESULTS Patients with a thrill at all three locations of the graft all had volume flows greater than 450 mL/min (negative predictive value = 100%). Of patients with a pulse at any of three locations, only 28% (positive predictive value) had a volume flow of 450 mL/min or less. CONCLUSION Physical examination is a good screening test for ruling out the low flows associated with impending access graft failure, thereby eliminating the need for routine US for many patients.

Diuretic-induced hypokalemia and cardiac arrhythmias.

Premature ventricular contractions have long been recognized as a complication of severe diuretic-induced hypokalemia. Likewise, diuretic-induced mild hypokalemia is known to have an arrhythmogenic potential in patients who are concurrently being treated with digitalis compounds. Recent studies using exercise and ambulatory monitoring of the electrocardiogram suggest that diuretic-induced premature ventricular contractions may be a more common phenomenon than was previously recognized. The risk of this form of ventricular ectopic activity is controversial. However, the available data are substantial enough to warrant some precautions on the part of the clinician.

THE RELATIONSHIP OF PROVIDER ORGANIZATIONAL STATUS AND ERYTHROPOIETIN DOSING IN END STAGE RENAL DISEASE PATIENTS

Controversy exists as to whether provider organizational characteristics such as profit status and setting are associated with the content of medical care or efficiency with which care is rendered. Following FDA approval of human recombinant erythropoietin (EPO) for use in clinical practice, Medicare approved coverage for beneficiaries in its end stage renal disease program and established a fixed payment per dose. Because cost of EPO administration varied positively with dose, providers could realize larger profit with prescription of smaller doses. We used Medicare claims data to assess EPO use by renal dialysis providers one year after FDA approval (June 1990) as a function of provider ownership (for-profit, not-for-profit, government agency) and setting (hospital-based, free-standing). Mean dose of EPO was 236 units greater (P =0.0001) for not-for-profit freestanding facilities, 593 units greater (P =0.0001) for government facilities, and 555 units greater for not-for-profit hospitals (P =0.0001 than among for-profit freestanding providers. With fixed payment per dose of EPO, for-profit, freestanding providers prescribed EPO more often and administered smaller doses than not-for-profit or government providers, behavior that is consistent with profit maximization.

Focal Segmental Glomerulosclerosis in Hodgkin’s Disease

Development of Nil disease and focal segmental glomerulosclerosis (FGS) in sequential renal biopsies is reported in a patient with Hodgkins lymphoma. Although steroid resistance was demonstrated, a complete and sustained clinical remission of the renal lesion followed anti-Hodgkins chemotherapy. These findings support the hypothesis that Nil disease and FGS are manifestations of the same clinical entity.

Association of chronic renal disease, hypertension, and infection with a rat-borne hantavirus

We report an association between past infection with an indigenous rat-borne hantavirus and chronic renal disease, hypertension, and cerebrovascular accidents among individuals using the Johns Hopkins Medical Institution from January 1986 through October 1988. A sample population of 1148 patients receiving quantitative total urine protein tests was screened for IgM and IgG antibodies to three different hantaviruses. Fifteen seropositives (1.3%) were found, of which 12 resided in inner city Baltimore in areas where Norway rats infected with a hantavirus had been captured.

Calcium Channel Blockade in Experimental Aminoglycoside Nephrotoxicity

Calcium channel blocker therapy has proved protective in certain models of ischemic‐induced acute renal failure. This effect may be related to the prevention of calcium influx into injured cells or by the vasodilatory effects of verapamil that may result in an improvement in renal blood flow. In the current study, the effect of verapamil treatment on the development of renal insufficiency and renal tissue calcium accumulation following aminoglycoside administration was investigated. The degree of functional damage and cortical tissue calcium accumulation after six or nine days of gentamicin administration (120 mg/kg body weight/day) was not significantly different in rats whose drinking water contained verapamil (10 mg/100 cc) than corresponding values in control animals. The tissue calcium accumulation correlated with the degree of reduction of creatinine clearance and probably reflects the extent of lethal tubular cell injury.

Medicare payment policy and recombinant erythropoietin prescribing for dialysis patients

The Medicare payment policy for recombinant human erythropoietin (rHuEPO) treatment for dialysis patients changed in January 1991 from a relatively fixed payment per treatment (allowed charge of

Percutaneous Transcatheter Recanalization in the Management of Acute Renal Failure due to Sudden Occlusion of the Renal Artery to a Solitary Kidney

40 per < or = 10,000 units injected) to a more variable payment based on the amount of rHuEPO administered with each treatment (allowed charge of