Neurite fasciculation mediated by complexes of axonin-1 and Ng cell adhesion molecule.

Neural cell adhesion molecules composed of immunoglobulin and fibronectin type III-like domains have been implicated in cell adhesion, neurite outgrowth, and fasciculation. Axonin-1 and Ng cell adhesion molecule (NgCAM), two molecules with predominantly axonal expression exhibit homophilic interactions across the extracellular space (axonin- 1/axonin-1 and NgCAM/NgCAM) and a heterophilic interaction (axonin-1-NgCAM) that occurs exclusively in the plane of the same membrane (cis-interaction). Using domain deletion mutants we localized the NgCAM homophilic binding in the Ig domains 1-4 whereas heterophilic binding to axonin-1 was localized in the Ig domains 2-4 and the third FnIII domain. The NgCAM-NgCAM interaction could be established simultaneously with the axonin-1-NgCAM interaction. In contrast, the axonin-1-NgCAM interaction excluded axonin-1/axonin-1 binding. These results and the examination of the coclustering of axonin-1 and NgCAM at cell contacts, suggest that intercellular contact is mediated by a symmetric axonin-12/NgCAM2 tetramer, in which homophilic NgCAM binding across the extracellular space occurs simultaneously with a cis-heterophilic interaction of axonin-1 and NgCAM. The enhanced neurite fasciculation after overexpression of NgCAM by adenoviral vectors indicates that NgCAM is the limiting component for the formation of the axonin-12/NgCAM2 complexes and, thus, neurite fasciculation in DRG neurons.

Oral clotrimazole in the treatment of esophageal candidiasis.

Several antifungal regimens had failed to relieve severe, recurrent esophageal candidiasis in a 75 year old woman without predisposing disease whose serum transiently inhibited the candidacidal capacity of her polymorphonuclear leukocytes. Treatment with oral nystatin suspension was unsuccessful, whereas intravenous amphotericin B and miconazole induced only transient responses. Oral 5-fluorocytosine induced severe nausea and vomiting, and was discontinued. Oral clotrimazole troches produced prompt and sustained eradication of the patient's candidal esophagitis.

Otitis media.

Earache, a common symptom in children, causes many parents to seek medical attention. Aside from trauma and the discomfort that often accompanies viral infections of the upper respiratory tract, acute otitis media with effusion is the commonest cause of otalgia in infants and children. Proper management requires a team effort between the physician and the child's parents or caretaker. The physician must transmit to the parents a concise but thorough overview of the problem and a plan for management. This should include information on the pathophysiology of ear disease, its incidence, therapy and the potential adverse effects, and any measures that the parents may take to prevent recurrence. The primary responsibility for transmittal of this information lies with the physician. Ancillary medical personnel and communication aids (videotapes, computers, printed materials) should be utilized, if available, to reinforce the physician's "message."

Fire ant envenomation in children.

Fire ants (Solenopsis richteri and Solenopsis invicta) have received scant attention from individuals other than agriculturists, entomologists, and victims of the bite and sting. Since their original importation into Mobile, Alabama, these small, seemingly benign, creatures have slowly migrated throughout most of the southern United States. Not unexpectedly, physicians working in the southern portions of the United States have been confronted with increasingly large numbers of patients, particularly children, who have been bitten and envenomated by these insects. Information regarding the pathogenesis of fire ant bite reactions and an approach to treatment are provided.

Urinary tract infections in young infants.

The clinical and laboratory features of urinary tract infections in 100 infants aged 5 days to 8 months are presented. Of the patients in the first three months of life 75% were boys, and of infants aged 3 to 8 months only 11% were boys; 95% of the infants were uncircumcised. Sepsis was documented in 31% of neonates, 21% of infants aged 1 to 2 months, 14% of those aged 2 to 3 months, and 5.5% of infants greater than 3 months of age. Roentgenographic abnormalities of the urinary system were found in 45% of female and 7% of male infants. All infants responded promptly to antimicrobial therapy. The possible factors related to the predominance of male infants with urinary tract infections in the first three months of life are discussed.

Organophosphate and carbamate poisoning in infants and children.

The clinical and laboratory features of moderate to severe organophosphate and carbamate toxicity in 37 infants and children are presented. Ingestion of an improperly stored liquid pesticide was the most common route of intoxication (76% of patients); five (14%) children became intoxicated after playing on carpets and floors of homes that had been sprayed or fogged by unlicensed exterminators. The transfer diagnoses were incorrect for 16 or 20 patients who were transferred to our center from another institution. Miosis (73%), excessive salivation (70%), muscle weakness (68%), and lethargy (54%) were the most common abnormal signs; 49% and 22% of patients had tachycardia and seizures, respectively, and 38% of children had respiratory insufficiency that required endotracheal intubation and mechanical ventilation. The results of erythrocyte and serum cholinesterase activity assays were concordant in 83% of patients. Thirty-four (92%) patients were treated with atropine and/or pralidoxime; three patients required only supportive care. Most patients had a prompt response to therapy; however, two patients with organophosphate toxicity required multiple doses of atropine during a 24-hour period; in both instances, the doses of atropine were subtherapeutic. There were no deaths. Pneumonitis and/or atelectasis developed in ten patients, including six who had ingested a petroleum distillate-containing insecticide.

Freshwater submersion injuries in children: a retrospective review of seventy-five hospitalized patients.

OBJECTIVE: To determine whether or not selected victims of submersion accidents can be safely managed as outpatients. DESIGN: Retrospective chart review. SETTING: Children's Medical Center of Dallas. PATIENTS: One hundred forty-eight charts reviewed, comprising all hospital admissions after submersion accidents from April 1987 to April 1994. RESULTS: Of the 148 patient charts that were reviewed, 73 patients were excluded from the study for the following criteria: endotracheal intubation before initial medical evaluation; transfer form an inpatient unit of another medical facility; history of preexisting neurologic, neurodevelopmental, and/or pulmonary disease. Of the 75 evaluable patients, 3 were directly admitted to the inpatient service with no documented initial medical evaluation reported in the medical record. Of the remaining 72 patients, 62 (86%) were symptomatic at the time of the initial medical evaluation in the emergency department; 10 patients (14%) were asymptomatic. Seventy percent of the initially asymptomatic patients and 57% of patients who were symptomatic at the time of initial medical evaluation were asymptomatic by 8 hours after the submersion event. By 18 hours postsubmersion, all patients who were initially asymptomatic and 72% of initially symptomatic patients were normal. Thirty-five percent and 80% of patients who had abnormal initial physical examinations and abnormal chest x-rays had a normal physical examination by 8 hours and 18 hours, respectively, and all remained normal. CONCLUSIONS: Routine hospital admission of all children who have had immersion accidents is unnecessary.

Pharmacokinetics of rifampin in infants and children: relevance to prophylaxis against Haemophilus influenzae type b disease.

Pharmacokinetic studies of rifampin were performed in 38 infants and children after administration of three different oral formulations. Mean peak serum concentrations of from 9 to 11.5 microgram/ml were observed one hour after a 10-mg/kg dose and the average half-life was 2.9 hours. Patients who received rifampin suspension in applesauce had smaller serum concentrations and area-under-the-curve values than did those who were given suspension alone. The mixture of rifampin powder and applesauce resulted in more variable serum levels. The concentrations of drug in tears from 18 subjects were similar to those in serum. All but one of 118 saliva specimens obtained from two to eight hours after the 10-mg/kg dose had antimicrobial activity. Of samples taken at two hours, 95% contained rifampin levels that exceeded the minimal bacterial concentration for 15 Haemophilus influenzae type b strains. Bactericidal activity against Haemophilus correlated with salivary rifampin concentrations and was detectable in virtually all specimens containing greater than or equal to 0.8 microgram/ml. These data provide the pharmacokinetic basis for rifampin prophylaxis of close contacts of H influenza type b disease, but are insufficient alone to recommend routine usage of rifampin for this purpose until results of additional epidemiologic studies are available.

Comparative pharmacokinetics of amoxicillin and ampicillin in infants and children.

The pharmacokinetics of amoxicillin and ampicillin were studied in 24 infants and children. Mean peak serum concentrations of 5.4 micrograms/ml in fasting and 3.2 micrograms/ml in nonfasting patients were observed after 15 mg/kg amoxicillin doses. Area under the curve values and serum half-life values were similar in fasting and nonfasting patients. The pharmacokinetics of amoxicillin (15 mg/kg) were compared to those of ampicillin (25 mg/kg). Peak serum concentrations, area under the curve values and half-life times were comparable for the two drugs. Amoxicillin (25 mg/kg) and ampicillin (25 mg/kg) were compared in cross-over fashion in 11 children. Serum concentrations of amoxicillin were consistently larger than those of ampicillin; the differences were of borderline significance at one and two hours and statistically significant at four and six hours after the dosage. The bioavailability of amoxicillin was twice that of ampicillin. Amoxicillin was detected in approximately half of the saliva samples studied. Although the salivary concentrations in many children exceeded the inhibitory level for most pneumococci and group A streptococci and for many non-beta lactamase-producing Haemophilus influenzae type b strains, the clinical relevance of these observations is unknown.

Report of 65 cases of Haemophilus influenzae b pneumonia.

During a 14-year period there were 65 cases of pneumonia caused by Haemophilus influenzae b; 83% were children less than 2 years of age and 80% of illness occurred in winter and spring. The roentgenographic picture was consolidative pneumonia in 75% and pleural effusions were present in 75% of all cases. Ten patients had associated meningitis and three had purulent pericarditis. Otitis media was diagnosed in 43% and H influenzae b was isolated from eight middle ear aspirates. Three patients (5%) died. Recommendations for diagnosis and treatment are made.

Evaluation of short-term antibiotic therapy in children with uncomplicated urinary tract infections.

This study was designed to determine whether serum C-reactive protein (CRP) concentrations could be used to identify children with uncomplicated lower urinary tract infection who would respond favorably to short-term antibiotic therapy. A one-day or ten-day regimen of cefadroxil (30 mg/kg/day in two divided doses) was assigned randomly to 80 children who had acute urinary tract infection and CRP concentrations less than 28 microgram/ml (CRP-negative group). Ten days of cefadroxil therapy was used to treat 44 children with urinary tract infection and CRP values greater than or equal to 28 microgram/ml (CRP-positive group). The clinical and laboratory characteristics of the children in the two CRP-negative therapy groups were similar to, but different from those of children with CRP-positive infections. Recurrent infections occurred significantly more often at four to five days after completion of therapy in CRP-negative children who received one day (44.4%) compared to ten days (20%) of cefadroxil therapy (P less than .05). When data from this study were combined with those from our previously published investigation of short-term antibiotic therapy in CRP-negative children, a significantly larger percentage of recurrences was documented immediately after one or four days of antibiotics (79%) compared to recurrences after the standard ten-day regimen (41%). Additionally, the total rate of recurrent infections for all children in both studies was significantly larger in those who received short-term therapy (48%) as opposed to conventional therapy (34%). These data indicate that short-term antibiotic therapy is less effective than the conventional ten-day regimen in children with CRP-negative urinary tract infection.

Serum penicillin concentrations after intramuscular administration of benzathine penicillin G in children.

Concentrations of penicillin were measured in serum samples of 26 children who received benzathine penicillin G (BPG) alone or in combination with procaine penicillin (PBPG). Both preparations were well absorbed; peak concentrations of penicillin after PBPG administration were 25-fold larger than those after BPG. One third and one half of serum samples from BPG and PBPG patients, respectively, contained no measurable penicillin activity at 18 days. At 30 days, there was no penicillin activity in any of the samples. These data raise questions regarding the use of BPG and PBPG for prophylaxis of group A streptococcal and pneumococcal infections.

Pharmacologic evaluation of orally administered antibiotics in infants and children: effect of feeding on bioavailability.

The clinical pharmacology of orally administered antibiotics was investigated in 106 infants and children. The antibiotic suspensions studied were ampicillin, cephalexin, erythromycin estolate, erythromycin ethylsuccinate, penicillin G, and penicillin V. The feeding status of the patients was evaluated in relation to the concentrations of drugs in serum, saliva, and tears. Peak concentrations and area-under-the-curve values of cephalexin, penicillin V, and penicillin G were reduced 40% to 60% in patients given milk and drug concurrently. Absorption was enhanced when erythromycin ethylsuccinate was given milk. After administration of both erythromycin formulations, penicillin V and ampicillin, salivary concentrations exceeded the minimal inhibitory concentrations for most pneumococci and group A streptococci and for many meningococci. The clinical implications of these pharmacokinetic data are discussed.

The contribution of uniparental disomy to congenital development defects in children born to mothers at advanced childbearing age.

Most instances of maternal uniparental disomy (UPD) start as trisomies and, similar to the latter, show a significant increase of mean maternal age at delivery. To investigate the incidence of UPD in offspring of older mothers, we investigated two groups of patients: 1) 50 patients with unclassified developmental defects born to mothers 35 years or older at delivery were tested for UPD for all autosomes by means of microsatellite marker analysis; 2) The incidence of UPD versus other etiologies in correlation, with maternal age below versus 35 years and above at delivery was studied in patients investigated in our laboratory for maternal UPD 15 (Prader-Willi syndrome, PWS), paternal UPD 15 (Angelman syndrome, AS), and maternal UPD 7 (Silver-Russell syndrome, SRS). In group 1, four patients of 50 showed UPD for an autosome that clarified the etiology of their developmental problems: a 27-year-old woman with growth retardation and early puberty disclosed maternal heterodisomy 14; a 15-year-old girl revealed paternal isodisomy 15; a 6-year-old boy with suspected Smith-Lemli-Opitz syndrome was shown to have maternal heterodisomy 16 with additional mosaic partial trisomy 16(pter-p13); a 16-month-old girl with intrauterine growth retardation and a dysmorphic pattern revealed maternal heterodisomy 7. In group 2 the offspring of older mothers showed a clear increase of UPD compared with the mothers below 35 years at delivery. The binomial distribution gave P-values of 1.9 x 10(-10), 2.6 x 10(-4), and 0.01 for PWS, AS, and SRS, respectively. The correlation between increase of paternal UPD 15 with advanced maternal age might be explained by maternal non-disjunction leading to hypohaploid gamete (nullisomy) for chromosome 15 with subsequent or concomitant duplication of the paternal homologue (paternal isodisomy). The three UPD 15 AS cases with mothers older than 35 years at delivery revealed isodisomy, whereas the three cases from younger mothers showed heterodisomy. This study confirms the hypothesis that uniparental disomy is a not negligible cause of congenital developmental anomalies in children of older mothers.

Surgical intervention for the complications of meningococcal-induced purpura fulminans.

Purpura fulminans is an infrequent but sometimes catastrophic illness that usually complicates a viral, rickettsial or bacterial infection. This communication presents a retrospective review of 152 patients with meningococcemia hospitalized at Children's Medical Center of Dallas from January, 1983, through December, 1993. Eighteen (11.9%) of the 152 patients developed purpura fulminans. Thirteen (72%) of the 18 patients with purpura fulminans needed one or more surgeries including skin grafts, local debridement, microvascular flaps or amputations. Five patients (28%) died.

Epidemiology and treatment of tinea capitis: ketoconazole vs. griseofulvin.

We studied 80 children with tinea capitis without kerion to define the epidemiology and clinical characteristics of tinea capitis and to compare the therapeutic efficacy of griseofulvin and ketoconazole for treatment of this disorder. Patients ranged in age from 2.1 to 11 years (median, 5.2 years). Trichophyton tonsurans (74%), Microsporum canis (13.5%) and Trichophyton mentagrophytes (2.7%) accounted for 90% of the infections. Pretreatment KOH slide preparations were positive in 69% of patients with alopecia and in only 29% of those with diffuse scale with little hair loss. Sixty-three patients were randomly assigned to receive ketoconazole (5 mg/kg/day) or griseofulvin (15 mg/kg/day). The treatment groups were comparable with regard to age, sex, duration of lesions prior to treatment and type of lesions. The percent of patients with positive cultures on therapy at 4, 6, 8, and 10 weeks and the mean time to a sterile culture were significantly larger (P less than 0.01) in ketoconazole (8 weeks) than in griseofulvin-treated (4 weeks) patients. The time for complete scalp clearing was significantly longer in patients who received ketoconazole (median, 108 days) compared with those who were treated with griseofulvin (median, 60 days) (P = 0.01).

Randomized controlled trial of intralesional corticosteroid and griseofulvin vs. griseofulvin alone for treatment of kerion.

We studied 30 children with tinea capitis and kerion to define the epidemiology of the disease and to compare the efficacy of intralesional steroid injection and griseofulvin to griseofulvin alone for treatment of this disorder. Patients ranged in age from 1 year to 12 years, 1 month (mean, 5 years, 7 months). All patients were black and 23 (77%) were female. (The racial composition of our clinic population is 45% black, 18% Latin American, 34% Caucasian and 3% Asian.) Fungus cultures were positive in all but one patient and Trichophyton tonsurans was isolated from 26 of 30 (87%) of the pretreatment hair cultures. Direct microscopic examinations of KOH-treated hair samples were negative in 13 of 29 (43%) culture-positive patients. Patients were randomly assigned to receive intralesional steroid injection (2.5 mg) and griseofulvin (14 patients) or griseofulvin only (16 patients). The treatment groups were comparable with regard to age, sex, duration of lesions before treatment and type of lesions. There were no significant differences between the two treatment groups in the time to negative culture, time of onset of new hair growth, complete regrowth of hair and time to scalp clearing. We conclude that intralesional injection of corticosteroid is an unnecessary adjunct to therapy for patients with tinea capitis with kerion.

The cumulative occurrence of resistance mutations in the HIV-1 protease gene is associated with failure of salvage therapy with ritonavir and saquinavir in protease inhibitor-experienced patients.

Salvage therapy with ritonavir (RTV) and saquinavir (SQV) failed to achieve virological and immunological improvement in 24 HIV-infected patients who discontinued triple therapy with RTV or indinavir (IDV) because of failure or intolerance to treatment. Changes in the HIV-1 protease gene sequence were analyzed prospectively in 14 patients. No primary protease mutation was found prior to the use of protease inhibitors. After 7 months of treatment with IDV or RTV, primary resistance mutations at codons pol 46 and/or pol 82 were observed in 11 of 13 patients. After 16 weeks on RTV-SQV, novel primary mutations related to SQV emerged in 7 of 13 patients, together with an increase in the number of secondary resistance mutations. Our observations indicate that the cumulative occurrence of resistance mutations in the protease gene was associated with failure of antiretroviral therapy. The presence of mutations to a first protease inhibitor may represent a risk factor for the failure of a subsequent treatment with a second line protease inhibitor.

Fever after craniofacial surgery in the infant under 24 months of age.

A retrospective review was undertaken of 126 consecutive craniofacial procedures involving a transcranial component, performed at the Children's Medical Center at Dallas, between 1990 and 1994. Standard postoperative axillary temperature measurements were recorded until discharge. Age at surgery of less than 24 months correlated very strongly with a postoperative temperature of greater than 38 degrees C (r = -0.92). The incidence of postoperative fever was high in all age groups, yet there was still a significant difference between the group younger than 2 years and the group in which surgery was performed after the age of 2 years across all postoperative temperature ranges, from >38 degrees C to >39.5 degrees C (p < 0.001, chi-square test). The white blood cell count was elevated above the age-related normal in 67 percent of febrile patients. There was no correlation between type or duration of surgical procedure, length of intensive care or hospital stay, or the need for blood transfusion and the development of a significant postoperative fever. There were minor infectious complications in four patients (3 percent), only one of which was a wound problem related to the surgery. All infectious complications were easily identifiable clinically. There was no mortality or serious infections. The development of postoperative fever, and an elevated white blood cell count, is to be expected in pediatric patients undergoing craniofacial procedures. The routine laboratory investigation of postoperative fever in pediatric craniofacial patients under 2 years of age without procedures involving transgression of the paranasal sinuses is not warranted unless there are associated clinical indicators.

Concentrations of antimicrobial agents in middle ear fluid, saliva and tears.

Antibiotics concentrations in middle ear fluid (MEF), saliva and tears were measured in children with persistent middle ear effusions undergoing tympanostomy tube placement. In 31 children given cefaclor, specimens of serum, saliva and MEF were collected at 0.5, 1, 2, 3 or 5 h after a dose. Another group of 37 children were randomized to receive a single dose of penicillin V, amoxicillin, ampicillin, erythromycin estolate, erythromycin ethylsuccinate, trimethoprim-sulfamethoxazole or cefaclor. Concentrations of antibiotics in saliva and tears bore no consistent relationship to those in MEF. Mean concentrations of all drugs in MEF were several-fold greater than the usual minimal inhibitory concentrations (MIC) of pneumococci, but only with trimethoprim and cefaclor were they greater than in usual MIC's for Haemophilus influenzae. Concentrations of antibiotics in MEF in persistent effusions were comparable to those previously reported in acute purulent effusions.