Donald Janner

Concentrations of procaine and aqueous penicillin in the cerebrospinal fluid of infants treated for congenital syphilis.

Penicillin concentrations in cerebrospinal fluid (CSF) were measured at various hours and days of treatment in 163 infants undergoing therapy for congenital syphilis. The CSF levels were compared for three treatment regimens. Aqueous penicillin G (A-PEN), 100,000 U/kg per day, was used in 23 infant, and a dosage of 200,000 U/kg per day was used in 40 patients; procaine penicillin G (P-PEN), 50,000 U/kg per day, was used in 100 children. Mean CSF penicillin levels were 0.416, 0.493, and 0.077 microgram/ml, respectively, in the three treatment groups. The mean CSF penicillin concentration among the 63 infants treated with either of the A-PEN regimens (0.465 microgram/ml) was significantly greater than the mean concentration (0.077 microgram/ml) among those treated with P-PEN (p < 0.001). Among those who received A-PEN, the difference in dosage was not associated with a significant difference in mean CSF penicillin concentration (p = 0.68). All the specimens obtained from patients who received A-PEN, but only 82% of those from patients who received P-PEN, had treponemicidal concentrations (> or = 0.018 microgram/ml). However, 33.3% (9/27) of specimens from infants who received P-PEN, tested between 18 and 24 hours after a dose, had CSF penicillin concentrations < 0.018 microgram/ml. These data suggest that administration of A-PEN may be the preferred therapy if CSF levels > 0.018 microgram/ml are desired, especially for infants with severe disease or congenital neurosyphilis.

Emergency department presentation and management of pediatric heart transplant recipients.

The object of this study was to review and delineate the presenting complaints, signs, symptoms, and Emergency Department (ED) management of pediatric heart transplant recipients who presented to Loma Linda University Medical Centers (LLUMC) Emergency Department. A retrospective chart review was made of all of the pediatric heart transplant patients who presented to the ED at LLUMC from January 1986 through February 1993. The department is part of a 600-bed university hospital with an associated 250-bed childrens hospital that includes a pediatric heart transplant center and an ED that sees over 38,000 patients per year. The retrospective review collected information relating to chief complaint, physical findings, laboratory analysis, and diagnoses. Forty-seven patients (23%) presented to the ED for a total of 76 visits. The patients presented a median of 278 days (range 19 days to 6.5 years) after transplantation. The most common chief complaints were related to the respiratory tract, and the most common diagnoses (55%) were related to infectious processes. Fever was present in 21% of the visits. Three of 13 blood cultures obtained were positive. Cardiac symptoms were present in 14% of the visits with two rejection episodes. Hospital admission was required for 22 (29%) of the ED visits. Results showed that pediatric heart transplant recipients are most likely to present to the ED with infections. Although infections from opportunistic organisms and bacteremia must be considered, most infections are similar to those in the nontransplanted child. Life-threatening conditions such as graft rejection are less likely. Nevertheless, the emergency physician should maintain caution in the evaluation of these patients. Close cooperation and consultation with the transplant team will assure the optimal outcome for these patients.

Familial juvenile autoimmune hypothyroidism, pituitary enlargement, obesity, and insulin resistance.

The proband, a 9-year-old Hispanic female, presented with hair loss, strabismus, and weight gain. On magnetic resonance imaging (MRI) she was found to have severe primary hypothyroidism and a large pituitary mass. In addition, acanthosis nigricans, obesity, and hyperinsulinism were observed. Findings were similar in three of four siblings. Thyroid peroxidase antibodies were detected in the father and three of four siblings. Although all family members were obese, and hyperinsulinemia with high proinsulin and C-peptide was found in all except one sibling, only the mother and one child had overt type 2 diabetes mellitus. Because of the unusual association of autoimmune thyroid disease, insulin resistance and obesity rather than insulin deficiency, we searched for possible genetic abnormalities. The HLA haplotypes did not cosegregate with autoimmune thyroid disease or insulin resistance. Mutational analysis of known obesity genes was done. Leptin was not deficient, and sequencing of the probands DNA showed no mutations in the perixisome proliferator activated receptor (PPAR)-gamma, PPAR-gamma(2), PPAR-alpha or melanocortin 4 receptor genes. Maternally inherited diabetes and deafness was ruled out since no mutations were found in mitochondria DNA. Insulin receptor antibodies were not detected. In conclusion, the remarkably high incidence of childhood autoimmune hypothyroidism, pituitary enlargement, insulin resistance and obesity in this family is not linked to known HLA types or known gene defects.

Efficacy and safety of ampicillin/sulbactam and cefuroxime in the treatment of serious skin and skin structure infections in pediatric patients

Background. Pediatric skin and skin structure infections are often polymicrobial and require empiric therapy effective against pathogens that may be resistant to many antimicrobial agents. The present study tested the efficacy and safety of a parenteral beta-lactam/beta-lactamase inhibitor combination, ampicillin/sulbactam, and a beta-lactamase-stable cephalosporin, cefuroxime, in serious pediatric skin and skin structure infections requiring hospitalization and parenteral antimicrobial therapy. Methods. This was a multicenter, randomized, prospective, comparative open label trial that enrolled patients 3 months through 11 years of age. Patients received 150 to 300 mg/kg/day ampicillin/sulbactam in equally divided intravenous doses every 6 h. Cefuroxime was given in a dosage of 50 to 100 mg/kg/day either intravenously or intramuscularly in equally divided doses every 6 or 8 h. Maximum treatment was not to exceed 14 days. Patients could receive subsequent oral antimicrobial treatment at the investigators discretion. Results. At final evaluation for clinical efficacy, 78.0% (n = 46) of the 59 evaluable patients who received ampicillin/sulbactam were cured and 22.0% (n = 13) were improved. The respective values for the 39 evaluable patients treated with cefuroxime were 76.9% (n = 30) and 23.1% (n = 9). At the end of treatment all pathogens were eradicated from 93.2% (n = 55) of 59 patients treated with ampicillin/sulbactam and from 100% of 39 who received cefuroxime. There were no significant differences between treatments in clinical or bacteriologic efficacy. Both ampicillin/sulbactam and cefuroxime were well-tolerated. Conclusion. Both ampicillin/sulbactam and cefuroxime provide safe and effective parenteral antibiotic therapy in pediatric patients with serious skin and skin structure infections.

Infected cardiac myxoma.

Infected cardiac myxoma is a rare condition with variable presentation. We report a case of infected cardiac myxoma which presented as fever of unknown origin. Diagnostic considerations and treatment of this condition are discussed.

Pediatric streptococcal toxic shock syndrome.

Two children who presented with fever, rash, and hypotension were found to have group A beta hemolytic streptococcal toxic shock syndrome. These cases are reported to remind physicians who care for acutely ill children that exotoxin-producing streptococci can produce clinical features and multisystem failure similar to staphylococcal toxic shock syndrome.

Non‐alcoholic steatohepatitis in a child with cartilage‐hair hypoplasia syndrome

We report an unusual pediatric case of cartilage‐hair hypoplasia (CHH) characterized by significantly impaired cellular immunity, recurrent sinopulmonary infections, severe non‐alcoholic steatohepatitis (NASH) and terminal liver failure. A 14‐year‐old boy was diagnosed clinically with CHH by age 1 year. His childhood was complicated by recurrent otitis media, bronchiectasis, and sinopulmonary infections due to bacteria and rare mold including Chaetomium. Immunological testing revealed absolute CD4 and CD8 count depletion. The diagnosis of CHH was confirmed by RNase mitochondrial RNA‐processing (RMRP) gene testing, which demonstrated not only the typical mutation at position c70 but an additional atypical mutation at position c213. By age 14, he had a 3‐year history of NASH. A diagnostic work‐up could not demonstrate any common etiologies for fatty liver including infectious,autoimmune, mitochondrial or metabolic etiologies. The terminal events of this childs life included hepatic failure and Chaetomium pneumonia. NASH involves the inability of hepatocytes to clear fat vesicles. CHH is largely a disorder of cellular proliferation. RMRP functions in mitochondrial DNA synthesis and in cleaving pre‐rRNA. This example of NASH with CHH raises the issue of whether the second, atypical mutation identified may be related to progressive liver disease, and whether the RMRP gene may have additional, currently unrecognized functions related to insulin resistance, liver metabolism or cellular immunity.