Bonheur Children's Medical Center Research Articles

Clinical and molecular characterization of S1118F‐CFTR

Cystic fibrosis is a lethal autosomal recessive disorder usually associated with lung disease, pancreatic insufficiency and high sweat chloride levels. A patient admitted to Le Bonheur Children's Medical Center (LBCMC, Memphis, TN) showed symptoms of meconium ileus which required exploratory laparotomy, bowel resection and ileostomy. Genotyping showed DeltaF508/I1027T on one chromosome and S1118F on the other. Sweat testing on three different occasions gave negative and intermediate results (22.7, 24.6 mmol/L; 55.1, 58.6 mmol/L and 55.1, 58 mmol/L) and pancreatic elastase testing showed normal levels. To characterize S1118F-CFTR mutation at a molecular level to help understand the associated CF-phenotype. Molecular characterization of S1118F-CFTR mutant was studied in HEK-293 cells at 37 degrees C. Various biochemical methods such as Western blotting, real-time PCR, Pulse chase labeling and iodide efflux assay were employed. S1118F-CFTR makes less than 10-15% of mature CFTR (band C) compared to WT-CFTR. The mRNA levels of S1118F-CFTR and WT-CFTR are comparable. S1118F-CFTR is functional but shows about 10-15% of WT-CFTR activity. S1118F-CFTR shows impaired maturation and CF-correctors can increase the amount of mature and functional CFTR by three- to fourfold. S1118F-CFTR shows impaired maturation and an individual with S1118F-CFTR paired with DeltaF508-CFTR exhibits atypical CF symptoms with intermediate sweat chloride level and meconium ileus despite documented pancreatic sufficiency.

Changing Patterns of Acute Hematogenous Osteomyelitis and Septic Arthritis

An increase in the incidence and severity of acute osteoarticular infections in children was perceived after the emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) in our community. This study was performed to describe changes in the epidemiology and clinical features of acute osteoarticular infections. The records of patients discharged from Le Bonheur Children's Medical Center with a diagnosis of acute osteoarticular infection between 2000 and 2004 were reviewed. Data regarding signs and symptoms, diagnostic testing, therapeutics, surgery, and hospital course were collected. There were 158 cases of acute osteoarticular infection. The incidence increased from 2.6 to 6.0 per 1000 admissions between 2000 and 2004. The proportion of infections caused by methicillin-susceptible S. aureus (MSSA) remained constant (10%-13%) and that caused by MRSA rose from 4% to 40%. There was no difference between MRSA and MSSA patients in the duration of fever or pain before diagnosis. Seventy-one percent of patients with MRSA had subperiosteal abscesses compared with 38% with MSSA (P = 0.02). Ninety-one percent of MRSA patients required a surgical procedure compared with 62% of MSSA patients (P < 0.001). Median hospital stay was 7 days for MSSA patients and 10 days for MRSA patients (P = 0.0001). Three patients developed chronic osteomyelitis, 2 with MRSA. There was no association between a delay in institution of appropriate antibiotic therapy and presence of subperiosteal abscess (P = 0.8). There has been an increase in the incidence and severity of acute osteoarticular infections in Memphis. Patients with community-associated MRSA infections are at higher risk of subperiosteal abscess requiring surgical intervention.

Short-term outcomes of severe lupus nephritis in a cohort of predominantly African–American children

Renal involvement is one of the major determinants of the outcome in patients with systemic lupus erythematosus. Although African-American ethnicity has been suggested to be a poor prognostic factor in severe lupus nephritis in adult patients, information on outcomes of African-American children with this disease is still very limited. We retrospectively studied the patients diagnosed with severe lupus nephritis by renal biopsy at Le Bonheur Children's Medical Center from January 1990 to December 2003. All patients were below the age of 18 years at the time of biopsy. Clinical features assessed included age, gender, race, estimated glomerular filtration rate (GFR), presence of hypertension, gross hematuria, degree of proteinuria, complement 3 and 4 levels, serum albumin, renal histology and dose of oral prednisone. Forty-four patients were studied: 82% were African-American and 89% were female. Mean age at biopsy was 14.2+/-3 years (median 15.0 years; range 4.7 years to 17.0 years). Renal biopsies were assessed according to the WHO classification. Twenty-seven percent, 43%, and 30% were in class III, IV and V, respectively. At presentation, 55% had hypertension and 23% had a history of macroscopic hematuria. The patients had varying degrees of proteinuria, including 18% with nephrotic syndrome. Eighteen percent had moderate renal insufficiency with estimated GFRs less than 50 ml/1.73 m2 body surface area per minute. All the patients were treated with corticosteroids. Sixty-eight percent also received cyclophosphamide and 20% received either mycophenolate mofetil (MMF) or azathioprine (AZA). Two patients developed end stage renal disease and required chronic dialysis within 12 months of biopsy. At the 12-month follow-up visit, 23% of patients had complete remission and 48% had partial remission. The mean estimated GFR had increased from 96.0 ml/1.73 m2 per minute to 124 ml/1.73 m2 per minute (P=0.03). Mean serum creatinine levels decreased from 1.62 mg/dl to 0.91 mg/dl (P=0.03). Complement 3 levels increased from 54.3 mg/dl to 90.3 mg/dl (P<0.01). Mean serum albumin levels also increased from 2.8 mg/dl to 3.6 mg/dl (P<0.01) and urine protein-to-creatinine ratio decreased from 5.8 to 1.0 (P<0.01). The average prednisone dose decreased from 0.96 mg/kg per day to 0.41 mg/kg per day (P=0.64). In our center, with predominantly African-American children, patients with lupus nephritis presented similarly to those in other studies with predominantly Caucasian patients, and short-term renal outcomes were not different.

C1q nephropathy: features at presentation and outcome

The study population comprised all 20 patients followed since 1990 through December 2004 at the Le Bonheur Children's Medical Center with diagnosis of C1q nephropathy (55% boys; 60% African Americans). All were aged under 18 years at biopsy (mean 11.2 years, 65% aged 11 or over); the youngest presented at age 10 months and progressed to end-stage renal disease at 14 months. None had clinical or laboratory features of systemic lupus erythematosis or membranoproliferative glomerulonephritis. Clinical features assessed at diagnosis were age, gender, blood pressure, history of macroscopic hematuria, urinary protein to creatinine ratio, serum creatinine, estimated glomerular filtration rate, renal histology, and pattern for immunofluorescent reactants. At the time of biopsy 40% had nephrotic syndrome and 30% nephrotic range proteinuria without nephrotic syndrome. Three patients with nephrotic syndrome also had chronic renal insufficiency at diagnosis. The most common histological feature was focal segmental glomerulosclerosis in 40%, but 30% had minimal change lesion. Four patients, all with nephrotic syndrome at diagnosis, progressed to end-stage renal disease. Of the 12 patients not presenting with nephrotic syndrome, none had chronic renal insufficiency at last follow-up. Kidney survival was 94% and 78% at 1 and 5 years, respectively, in all patients and 88% and 49% in those presenting with nephrotic syndrome.

Appropriateness of Anticonvulsant Concentration Monitoring In Hospitalized Pediatric Patients

We assessed the appropriateness of anticonvulsant concentration monitoring in hospitalized pediatric patients admitted to a teaching hospital. Literature-based criteria for anticonvulsant concentration monitoring were approved by the Pharmacokinetic and Neurology Services of Le Bonheur Children's Medical Center. A random sample of anticonvulsant concentrations ordered over a 6 month period was assessed. Patient demographics, anticonvulsant data, the type of professional who recommended the concentration, and sampling time were collected concurrent with hospitalization. Concentrations were assessed for appropriateness of indication and sampling time. Concentrations (n=141) were obtained in 74 patients (mean age = 6.5+5.5 years) admitted to the floor (86%) or ICU (14%). Length of stay was 8.3+16.9 days. Monotherapy was used in 78.3% of patients. Carbamazepine (28.4%), phenytoin (27.5%), phenobarbital (27.6%), valproate (14.8%) or free phenytoin (1.7%) concentrations were recommended by a pediatrician (70.5%), neurologist (21.5%), neurosurgeon (2.1%), or Pharmacokinetic Services (5.9%). Fifty-three percent of all concentrations met appropriateness criteria for indication; however, 8.5% of tests were collected incorrectly. About half of the concentrations recommended by pediatricians (47.5%), neurologists (43.3%), and neurosurgeons (66.7%) did not meet appropriateness criteria for indication. The main reasons for inappropriate anticonvulsant concentration monitoring include frequent repetitive sampling (<24 hours), obtaining an anticonvulsant concentration without an appropriate indication, failure to correctly apply the concept of pharmacological steady-state, incorrect identification of drug-drug interactions, and sampling irrespective of dosing schedule. One-half of all anticonvulsant concentrations fulfilled the indication criteria. There was no difference in appropriateness of indication based on the service recommending the concentration or for each specific anticonvulsant. The appropriateness rates reported are comparable to those reported in other studies. Inappropriate anticonvulsant concentration monitoring fails to improve patient care and contributes to a significant waste of financial resources.

Mark Timothy (Tim) Parris, Ms: A Conversation with the Editor

Tim Parris, president of Baylor University Medical Center (BUMC), was born on August 23, 1956, in Jackson, Mississippi, where he grew up (Figure ​(Figure11). He graduated from the University of Southern Mississippi in Hattiesburg in 1978 and received a master of science degree in hospital and health administration from the University of Alabama at Birmingham in 1981. After completing a hospital administrative residency at BUMC, he remained on the staff and soon became executive director of the Baylor Institute for Rehabilitation. In 1985, he was awarded a White House fellowship and spent 1 year in the executive office of the president, working in the Office of Management and Budget under the Honorable James C. Miller III. After that year, he became chief operating officer of Le Bonheur Children's Medical Center in Memphis, Tennessee. In 1990, he was offered a senior administrative position at the University of North Carolina Medical Center in Chapel Hill and at the same time was offered a vice presidency position at BUMC. Fortunately for us, he chose the latter position, where he rapidly rose to senior vice president, executive vice president, and, in January 2000, to his present position. Tim Parris is a man of action. In his calm and decisive way, he has his finger on essentially all BUMC activities. We are fortunate to have a man of his talents managing the day-to-day operations of this complex medical center. He is also a good guy.

The maintenance need for water in parenteral fluid therapy.

In the category of genitourinary and fluid and electrolyte disorders, no paper bridges the discoveries of the 1930s through the 1950s and the practice of today as does the classic paper of Holliday and Segar.1 Today house officers and staff physicians use this same simple method for estimating insensible and urinary water losses of a child or adult of any size or age. Current textbooks and the latest editions of commonly used house officer manuals use this method of determining maintenance water needs based on calorie expenditure.2-5 This method involves a simple formula that relates the average calorie expenditure of a … Address correspondence to Russell W. Chesney, MD, University of Tennessee, Memphis; Le Bonheur Children's Medical Center, 50 N Dunlap, Room 306, Memphis, TN 38103.

Prediction of Serum Albumin Concentration after Albumin Supplementation in Pediatric Patients Receiving Parenteral Nutrition EMILY B. COCHRAN, SUSAN L. HOGUE Le Bonheur Children's Medical Center, Memphis

Nutrition in Clinical PracticeVolume 7, Issue 1 p. 43-43 Article Prediction of Serum Albumin Concentration after Albumin Supplementation in Pediatric Patients Receiving Parenteral Nutrition EMILY B. COCHRAN, SUSAN L. HOGUE Le Bonheur Children's Medical Center, Memphis Charles W. Jastram Jr, Charles W. Jastram JrSearch for more papers by this author Charles W. Jastram Jr, Charles W. Jastram JrSearch for more papers by this author First published: 01 February 1992 https://doi.org/10.1177/088453369200700115AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume7, Issue1February 1992Pages 43-43 RelatedInformation

Bronchogenic cysts: A cause of stridor in the neonate

Bronchogenic cyst of the mediastinum, a cause of stridor in the neonate, is one of a group of congenital lesions of the mediastinum that results from abnormal budding of the ventral segment of the primitive foregut. A review of our treatment of 15 patients over 10 years at Le Bonheur Children's Medical Center is highlighted by a case report of a newborn with stridor and severe respiratory distress caused by a mediastinal bronchogenic cyst. We assess the literature on these rare but life-threatening lesions, and discuss the embryology, diagnostic work-up, and treatment, emphasizing the roles of different radiologic modalities in evaluating patients.

A prospective, randomized, double-blind comparison of calcium chloride and calcium gluconate therapies for hypocalcemia in critically ill children

Disturbances of ionized calcium levels have been reported in sick neonates, l and we have found a high rate of occurrence of ionized hypocalcemia, 2 which was associated with a significantly increased mortality rate in critically ill nonneonatal pediatric patients. Calcium chloride and calcium gluconate are two of the standard salt preparations that are used to correct hypocalcemia; the former is usually preferred because it is in the ionized form and therefore provides more readily available ionized calcium for use. In this study, critically ill pediatric patients with ionized hypocalcemia received either calcium chloride or calcium gluconate in a randomized manner. The purposes of this study were (1) to determine whether calcium chloride and calcium gluconate provide equal bioavailability of ionized calcium and (2) to assess whether there were any differences in physiologic effects after administration of the two salts. METHODS Patient selection. All patients admitted to the Le Bonheur Children's Medical Center intensive care unit were eligible for participation in this study if they were found to have hypocalcemia. Patients were enrolled in the study after informed consent was obtained in compliance with the investigational review boards of the University of Tennessee and LBCMC. Exclusion criteria were (1) calcium administration before arrival in the ICU and (2) no documentation of

MENINGTS CAUSED BY AMPICILLIN AND CHLORAMPHENICOL-RESISTANT HAEMOPHILUS INFLUNZAE

Department of Pediatrics The University of Tennessee, Memphis College of Medicine Le Bonheur Children's Medical Center

Comparison of a Pediatric versus Standard Amino Acid Formulation in Preterm Neonates Requiring Parenteral Nutrition R.A. HELMS, M.L. CHRISTENSEN, E.C. MAUER, AND M.C. STORM Department of Clinical Pharmacy and the Center for Pediatric Pharmacokinetics and Therapeutics, University of Tennessee, Memphis; Le Bonheur Children's Medical Center, Memphis; and the Research Department, Kendall McGaw Laboratories, Inc., Irvine, California

Nutrition in Clinical PracticeVolume 2, Issue 5 p. 217-217 Article Comparison of a Pediatric versus Standard Amino Acid Formulation in Preterm Neonates Requiring Parenteral Nutrition R.A. HELMS, M.L. CHRISTENSEN, E.C. MAUER, AND M.C. STORM Department of Clinical Pharmacy and the Center for Pediatric Pharmacokinetics and Therapeutics, University of Tennessee, Memphis; Le Bonheur Children's Medical Center, Memphis; and the Research Department, Kendall McGaw Laboratories, Inc., Irvine, California Elizabeth Gilmore, Elizabeth GilmoreSearch for more papers by this author Elizabeth Gilmore, Elizabeth GilmoreSearch for more papers by this author First published: 01 October 1987 https://doi.org/10.1177/088453368700200512AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume2, Issue5October 1987Pages 217-217 RelatedInformation

Glioblastoma in children.

Both morphologic and clinical features of 72 consecutive cases of brain tumors, collected over 9 years at Le Bonheur Children's Medical Center, were reviewed. We identified 11 cases as glioblastoma, representing 16% of all intracranial neoplasm and 26% of glial tumors. The patients ranged in age from 1 to 15 years with the median age of 10 years. There were 4 females and 7 males; 2 blacks and 9 whites. The median survival was 9 months. The tumor was observed in both cerebrum and cerebellum. Sexual predominance was not appreciable, although there was male excess. The tumor was significantly more frequent in whites than blacks (p less than 0.05). Similar racial predominance was noted in the other, more common brain tumors in children such as astrocytoma and medulloblastoma.

EXERCISE CONDITIONING IN CHILDREN WITH ASTHMA

Cardiopulmonary Physiology Lab., Department of Pediatrics, University of Tennessee Center for the Health Sciences, and Le Bonheur Children's Medical Center, Memphis, TN 38103.

EXERCISE TESTING IN CHILDREN WITH ASTHMA

Cardiopulmonary Physiology Lab., Department of Pediatrics, University of Tennessee Center for the Health Sciences and Le Bonheur Children's Medical Center, Memphis, TN 38103.

EXERCISE CONDITIONING IN CHILDREN WITH ASTHMA

Cardiopulmonary Physiology Lab., Department of Pediatrics, University of Tennessee Center for the Health Sciences, and Le Bonheur Children's Medical Center, Memphis, TN 38103.

Handguns and Children

Le Bonheur Children's Medical Center and the Departments of Pediatrics and Community Medicine, University of Tennessee Center for the Health Sciences