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Biomedical subjects

Michael L Moritz

Publications and source records attributed to Michael L Moritz.

27 records · Page 2Linked to original sources

Quantitative viral load monitoring and cidofovir therapy for the management of BK virus-associated nephropathy in children and adults.

BACKGROUND: BK virus (BKV)-associated nephropathy (BKVAN) has been increasingly recognized as an important cause of renal transplant dysfunction. We report the role of quantitative viral load monitoring in the management of BKVAN. METHODS: We developed a real-time quantitative polymerase chain reaction (PCR) assay for BKV detection in urine and plasma. Four renal allograft recipients, including two children, with BKVAN were treated with low-dose cidofovir and followed prospectively. RESULTS: The PCR assay showed a detection limit of 10 viral copies with an intra-assay coefficient of variation of 19%. All four patients with BKVAN demonstrated intranuclear inclusions on allograft biopsy and a progressive rise in serum creatinine; three patients underwent multiple biopsies before the diagnosis of BKVAN was made. Three of the patients experienced a "viral syndrome" before the onset of renal dysfunction. One child also demonstrated an echogenic renal mass. All of the patients demonstrated strongly positive urinary PCR values (>100,000 copies/microL). BKV DNA was also detected in the plasma of three patients. All the patients were treated with intravenous low-dose cidofovir (0.25-1 mg/kg per dose, every 2-3 weeks, without probenecid). BK viruria resolved within 4 to 12 weeks (after 1-4 doses) of the cidofovir therapy, and all patients remain with stable renal function 6 to 26 months posttherapy. CONCLUSIONS: Quantitative PCR for BKV is a sensitive and reliable method for following the course of the infection in renal transplant patients. In addition, cidofovir therapy may be useful in the treatment of some of these patients, and its role needs to be investigated further.

Adult↗

Long-term antiproteinuric and renoprotective efficacy and safety of losartan in children with proteinuria.

BACKGROUND: Angiotensin receptor antagonists are effective in reducing proteinuria by an action independent of blood pressure. As a consequence, such agents retard progressive renal dysfunction in adults with chronic proteinuria. Long-term efficacy and tolerability data in children are unavailable. METHODS: Efficacy of losartan in reducing proteinuria and in preserving renal function was prospectively assessed in 52 consecutive children under 18 years of age with chronic proteinuric renal disorders, an initial creatinine clearance > or =25 mL/min/1.73 m(2), and a minimum of two or more follow-up visits. Thirty had proteinuria (P), and 22 had proteinuria combined with hypertension (P+H). Adverse effects were also evaluated. RESULTS: Proteinuria had persisted or increased during a mean interval of 8.5 months before initiation of losartan at a mean dosage of 0.8 mg/kg/d. Mean protein excretion before starting losartan was 2453 mg/m(2)/d and fell by 34% at a mean follow-up time of six weeks (visit I, P<.05), and between 64% and 67% at mean follow-up periods of 0.38, 0.71, and 2.48 years corresponding to visits II, III, and IV (all P<.001 compared with baseline). The proportion of children with protein excretion exceeding 40 mg/m(2)/h (nephrotic range proteinuria) or nephrotic syndrome (>3500 mg/1.73 m(2)/d) fell from 42% and 40% at the start, to 24% and 8%, respectively, at visit IV (P<.01). Mean creatinine clearance as well as serum potassium and total CO(2) levels remained unchanged during the time of follow-up. Reduction in proteinuria in the P subgroup alone correlated with lowering in diastolic blood pressure at visit II and with both diastolic and systolic blood pressure at visits III and IV (all P<.05); it was largely independent of reduction in blood pressure in the P+H subgroup. The concomitant use of immunosuppressive agents in 28 of the 52 children had an influence on proteinuria only at baseline and at visit I (P<.05). There was no significant change in height or body mass index Z scores. Thirteen children had adverse effects potentially ascribed to losartan; most of these either improved or resolved with dosage adjustment or resulted in its discontinuation in 9 of the 52 children (17%). CONCLUSION: Losartan therapy was associated with a marked and sustained reduction in proteinuria and in preservation of GFR in children with chronic proteinuric disorders. The association between proteinuria and systemic blood pressure reduction was complex: it was largely limited to the first year of losartan therapy and was more pronounced in the normotensive subgroup. Losartan was generally well tolerated.

Adolescent↗

Prevention of hospital-acquired hyponatremia: a case for using isotonic saline.

OBJECTIVE: The current standard of care in pediatrics is to administer hypotonic saline in maintenance parenteral fluids. The safety of this approach has never been evaluated. METHODS: A review of the literature reveals that the administration of hypotonic fluids is potentially dangerous and may not be physiologic for the hospitalized child. RESULTS: There have been >50 reported cases of neurologic morbidity and mortality, including 26 deaths, in the past 10 years resulting from hospital-acquired hyponatremia in children who were receiving hypotonic parenteral fluids. Common childhood conditions requiring parenteral fluids, such as pulmonary and central nervous system infections, dehydration, and the postoperative state, are associated with a nonosmotic stimulus for antidiuretic hormone production, which can lead to free water retention and hyponatremia. Children are at particularly high risk of developing symptomatic hyponatremia as they have a larger brain-to-skull size ratio. CONCLUSIONS: The administration of isotonic saline in maintenance parenteral fluids is the most important prophylactic measure that can be taken to prevent the development of hyponatremia in children who receive parenteral fluids.

Cross Infection↗

Systemic anticoagulation and bleeding in children with hemodialysis catheters.

Hemodialysis catheters are routinely flushed with high-concentration heparin solutions to maintain intradialytic patency. The safety of this practice has never been established. This report describes five patients with hemodialysis catheters who were found to be inadvertently systemically anticoagulated perioperatively and had bleeding complications. These patients all had normal preoperative coagulation panels drawn peripherally. Smaller children managed by hemodialysis may be at greater risk for systemic anticoagulation and bleeding than older children and adults from high-concentration heparin flush solutions, particularly during the perioperative period. Guidelines are presented to prevent hemorrhagic complications from inadvertent systemic anticoagulation.

Adolescent↗

Survival with hypopituitarism from congenital syphilis.

Congenital syphilis continues to occur despite the advances in testing of pregnant women in many countries and the availability of penicillin since 1943. This is a report of a child with multiple systemic manifestations of congenital syphilis. This is one of the few cases of survival with pituitary involvement from congenital syphilis and the first noted case in which diabetes insipidus developed. Institution of routine testing in all countries might have prevented the severe manifestations of syphilis seen in this child.

Disease-Free Survival↗