Gershon Alpert

Direct Measurement of TP/GFR: A Simple and Reliable Parameter of Renal Phosphate Handling

As the Walton-Bijvoet nomogram for estimating renal phosphate (P) threshold (TmP/GFR) is not applicable to children of all ages, we sought an alternative method for measuring renal handling of P. Recognizing that the nomogram represents an indirect correlation between TmP/GFR and TP/GFR under fasting conditions, we examined this directly in 26 children. An excellent correlation was found, expressed as TmP/GFR = (fasting TP/GFR X 1.1) -0.3 (r = 0.95). The regression line in adults, expressed as TmP/GFR = (fasting TP/GFR X 1.4) -0.9 (calculated from published studies) is markedly different at the higher values typical for children. Since no advantage could be seen in the use of a mathematically derived TmP, we investigated the direct use of measured TP/GFR (tubular P reabsorption per 100 ml glomerular filtrate) as a measure of renal P handling in clinical practice. No differences were found between morning fasting and nonfasting values. Measurements in 151 healthy subjects aged 3 days to 53 years established normal values in relation to age. The use of this parameter in patients is shown to accurately reflect defects and changes in renal P handling. We believe it to be the preferred parameter because it represents a directly measured physiologic function applicable to all age-groups.

Lifestyle Intervention in Obese Arab Women: A Randomized Controlled Trial

BACKGROUND Few randomized controlled trials on lifestyle interventions have been reported in non-Western populations; none have been reported in Arab populations. METHODS From 2 Muslim Arab communities in Israel, obese, nondiabetic women aged 35 to 54 years with 1 or more components of the metabolic syndrome were randomized to either an intensive (n = 100) or a moderate (control) (n = 101) 12-month lifestyle intervention. Women in the intensive intervention had 11 individual and 11 group counseling sessions per year with a dietitian and 22 physical activity group sessions per year. Women in the moderate intervention had 3 individual and 2 group dietary counseling sessions per year and no guided physical activity. Cultural issues were addressed in the design and conduct of both interventions. The primary outcome measure was change in the metabolic syndrome and its components. RESULTS At 12 months, the intensive intervention group had median declines of 3.0 mg/dL (to convert to millimoles per liter, multiply by 0.0555) in fasting plasma glucose and 4.5 mg/dL (to convert to millimoles per liter, multiply by 0.0113) in triglyceride levels compared with median increases of 1 mg/dL in fasting plasma glucose and 5.8 mg/dL in triglyceride levels in the moderate intervention group (P = .01 and P = .02, respectively). The median waist circumference decreased by 5.4 cm in the intensive intervention group and by 3.1 cm in the moderate intervention group (P = .10). The prevalence of the metabolic syndrome decreased by 4.0% in the intensive intervention group and increased by 5.2% in the moderate intervention group (P = .12). CONCLUSION The 12-month culturally sensitive intensive lifestyle intervention was effective in improving some of the metabolic syndrome components in obese Arab women. Trial Registration clinicaltrials.gov Identifier: NCT00273572.

Vancomycin pharmacokinetics in infants: relationships to indices of maturation.

The relationships between steady state pharmacokinetics of vancomycin and various indices of maturation were examined in 11 infants (gestational ages, 27 to 40 weeks; postconceptional ages (PCA), 29 to 48 weeks). Vancomycin was administered as a 10-mg/kg iv infusion over 30 minutes. Serial blood samples were obtained over a dosage interval and vancomycin serum concentrations were determined by fluorescence polarization immunoassay. Model-independent pharmacokinetic data analysis yielded values for vancomycin systemic clearance (CL), volume of distribution (Vdss) and half-life ranging from 0.032 to 0.484 liter/hour, 0.44 to 2.5 liters and 3.5 to 9.6 hours respectively. Stepwise multiple regression analysis indicated that PCA was the best single variable model to predict vancomycin clearance as described, namely: CL (liters/hour) = 0.0224 PCA (weeks) - 0.639 (r = 0.91; P less than 0.0001). Other more complex models using a combination of patient variables only modestly improved the ability to explain the variability in vancomycin clearance. Vdss was strongly related to body weight (r = 0.93; P less than 0.0001) Vdss = 0.563 weight (kg) + 0.052). Our results suggest that postnatal alterations in vancomycin disposition are related to maturational changes in body composition and renal function. These data also suggest that vancomycin doses smaller than those previously recommended may be used to achieve therapeutic steady state vancomycin serum concentrations during the first 2 months of life.

Complications of infection with Epstein-Barr virus during childhood: a study of children admitted to the hospital.

We undertook a study of infection with Epstein-Barr virus (EBV) in order to ascertain the spectrum of complications from this disease. During a 6-year period, 51 children were admitted; review of the 50 available records confirmed the diagnosis of EBV infection in 48, 37 of whom had clinical infectious mononucleosis. The indications for admission were diagnostic evaluation in 14 (29%) children, airway obstruction in 12 (25%) children, dysphagia and dehydration in 11 (23%) children, airway obstruction and dehydration in 2 (4%) children, severe malaise in 2 (4%) children, pneumonia in 2 (4%) children, encephalitis in 2 (4%) children, Guillain-Barré syndrome in 1 (2%) child and unrelated conditions in 2 (4%) children. Additional complications developing during hospitalization included peritonsillar abscess, pancytopenia, pleural effusion, hepatitis and hyponatremia. We believe that infection with EBV has a higher morbidity in childhood than previously appreciated.

Single Intramuscular Dose of Ceftriaxone as Compared to 7-Day Amoxicillin Therapy for Acute Otitis Media in Children

Fifty-two children (mean age 23 months) with acute otitis media were treated randomly with either a single intramuscular dose of ceftriaxone (Rocephin) 50 mg/kg (27 patients) or 7 days of amoxicillin 12.5 mg/kg t.i.d. (25 patients). The rate of resolution of acute symptoms and incidence of recurrences and relapses during the first months after commencement of the therapy was similar in the two groups. One week following the start of treatment no difference was observed in the proportion of patients with tympanometric evidence of middle ear effusion (MEE) in either of the two groups. On day 30, however, significantly more patients from the ceftriaxone group had flat tympanograms-83% as compared to 47% in the amoxicillin group. Therefore, single-dose ceftriaxone therapy cannot be suggested at present as routine therapy for acute otitis, although it may be considered a reasonable alternative in noncompliant patients.

Outbreak of fatal adenoviral type 7a respiratory disease in a children's long-term care inpatient facility

Adenoviruses are a common cause of respiratory diseases. Types 7,3, and 21 may cause a particularly serious and even fatal illness, especially in children. Outbreaks of adenovirus infection have been documented in military training populations, in a family setting, and as a nosocomial infection in a children’s home,’ pediatric wards,” 3 and a surgical intensive care unit.4 We report an adenovirus 7a outbreak in a pediatric long-term care inpatient facility. Four patients with symptoms, three patients without symptoms, and two personnel with symptoms were found to be infected with adenovirus type 7a. A high susceptibility to infection with adenovirus and a high mortality rate were documented in this population of chronically sick infants.

Case-control study of hyperpyrexia in children

To test the association of hyperpyrexia (temperature ≥41.1°C) with increased rates of bacteremia and serious bacterial illness in young children, we performed a retrospective case-control study. Seventy-six hyperpyrexic children and an equal number of control cases with temperatures of 39.1–40° and 40.1–41.0° were identified. A significantly larger number of diagnostic procedures including blood cultures, urine cultures, chest x-rays and white-blood cell counts were performed in the hyperpyrexic children (P < 0.05). The frequency of serious bacterial infections and bacteremia did not differ among the groups (P > 0.05). Hyperpyrexic children need to be evaluated as thoroughly and carefully as any other febrile child but do not merit special consideration.

Risk of infection during adrenocorticotropic hormone treatment in infants with infantile spasms.

We reviewed the clinical features and laboratory findings of 27 infants with infantile spasms treated with adrenocorticotropic hormone or prednisone during febrile episodes in order to evaluate the incidence of bacteremia, the risk of serious infection, determination of whether serious infections can be identified at presentation and the outcome of febrile episodes. There were 75 febrile episodes including 4 episodes of identified bacteremia (5.3%). Three children who were treated with adrenocorticotropic hormone dosage larger than recommended died. Leukocytosis and a differential count with many immature granulocytes predicted bacteremia in this population. Chest radiography was useful in identifying the cause of fever. The pathogens isolated were similar to those found in this age range. We conclude that the frequency of bacteremia in our patient population is similar to that observed in infants of the same age; however, the outcome is frequently fatal. In addition this increased mortality may be associated with the use of a larger dosage of adrenocorticotropic hormone than recommended.

Effect of a human immunoglobulin preparation for intravenous use in a rabbit model of meningococcal endotoxin-induced shock

Background and Methods:Endotoxin shock is mediated by various cytokines, including tumor necrosis factor. Treatment of patients with iv immunoglobulin has been shown to reduce the concentration of circulating cytokines. The purpose of this study was to determine the protective effects of immunoglobulin for iv use on meningococcal endotoxin-induced shock in a rabbit model. Experimental animals were challenged with iv meningococcal endotoxin (lipo-oligosaccharide) 10 μg/kg, and treated with either a 2-hr iv immunoglobulin infusion (400 mg/kg) or a similar saline infusion that was initiated 30 mins before endotoxin challenge. Control animals were challenged with saline alone. Results:Compared with untreated control animals, pulse rate increased (p < .007) and mean arterial pressure and serum bicarbonate concentrations decreased (p < .02) in both experimental groups, but did not differ between immunoglobulin-treated and saline-treated animals (p > .05) at any time after the endotoxin challenge. Geometric mean serum endotoxin concentrations were significantly (p < .03) lower in the immunoglobulin-treated animals at 60,120, 180, 240, 300, and 360 mins after the endotoxin challenge. The geometric mean serum tumor necrosis factor level at 1 hr after the endotoxin challenge in the immunoglobulin-treated experimental animals was lower than in saline-treated animals (5.53 vs. 8.47 tumor necrosis factor enzyme-linked immunosorbent assay U/mL), but not significantly so (p > .05). Mortality rate was similar in both experimental groups; eight (67%) of 12 saline-treated experimental rabbits and seven (70%) often immunoglobulin-treated rabbits died. All untreated control animals survived 24 hrs. Conclusions:In this model of circulatory shock in rabbits, iv immunoglobulin: a) does not significantly alter the physiologic responses to endotoxin challenge; b) significantly reduces endotoxin concentrations; c) reduces tumor necrosis factor concentrations, but not significantly; and d) does not improve survival rate.

Inhibition of human neuroblastoma development in nude mice by use of monoclonal antibodies

The human neuroblastoma cell line LA-N-1 may form subcutaneous tumors in nude mice. The purpose of this study was to evaluate passive immunotherapy of human neuroblastoma using 390 monoclonal antibody that detects Thy-1 determinant on the cell surface of LA-N-1 neuroblastoma cells. The effect of the 390 antibody alone and combined with complement was tested in nude mice of NIH Swiss background and BALB/c, nu/nu mice challenged with different dosages of LA-N-1 tumor cells. Intraperitoneal administration of anti Thy-1 monoclonal antibody of the IgG2 class has prevented the appearance of subcutaneous LA-N-1 neuroblastoma tumors as evidenced by a very low incidence of tumors in nude mice treated daily, intraperitonealy, with 2 mgr IgG2 of monoclonal antibody 390 and 0.1 ml rabbits complement. In the very few nude mice developing LA-N-1 neuroblastoma tumors under treatment, tumor development required a long latency period compared to control animals. The anti Thy-1 monoclonal antibody had no effect on survival...