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Biomedical subjects

E Nussbaum

Publications and source records attributed to E Nussbaum.

At least 37 records · Page 2Linked to original sources

Usefulness of miniature flexible fiberoptic bronchoscopy in children.

A miniature flexible fiberoptic bronchoscope (FFB) (Olympus BF-N20) (2.2 mm diameter) was applied to 53 children (20 female subjects) ranging in age from 3 months to 15 years (mean, 4.19 years). Most common indications for bronchoscopy included stridor or weak cry and persistent wheezing or cough unresponsive to inhaled bronchodilators, chest physiotherapy, steroids, and antimicrobial agents. There were no complications. In 38 children (71.6 percent) it was diagnostically useful, particularly for the investigations of upper airway obstruction (66 percent). In 22 children (41.5 percent) it provided guidance for surgical interventions. The instrument was particularly useful during its application in infants with severe upper airway obstruction who otherwise would require open rigid-tube bronchoscopy in the operating room. It was of limited value when excessive bronchial secretions obstructed the view of the working field for which a bronchoscope with a built-in suction channel was needed. It is concluded that this miniature FFB is a useful diagnostic tool in infants and children particularly for obstructed upper airways but has limited applications in children with peripheral airway disease. The 2.2-mm bronchoscope may have its greatest advantage in preterm neonates and intubated infants, where the small glottic or endotracheal tube size renders the 3.5-mm bronchoscope useless.

Adolescent↗

Continuous end-tidal CO2 in pediatric bronchoscopy.

In recent years flexible fiberoptic bronchoscopy (FFB) has been applied to children for diagnostic and therapeutic purposes. Sedation during FFB, along with introduction of the bronchoscope into the pediatric airway, may cause hypoventilation, leading to hypoxia and desaturation, even in the presence of oxygen supplementation. Arterial oxygen saturation is usually monitored by pulse oximetry (SpO2) during FFB. End-tidal PCO2 (P(etCO2)) monitoring is not routinely used. Twenty-two pediatric patients (15 days to 18 years old) undergoing FFB and receiving supplemental oxygen were studied prospectively and had continuous P(etCO2) and SpO2 measured before and during the procedure (bronchoscope at the carina or either main bronchus). Mean P(etCO2) (+/- SD) decreased from 33.9 (+/- 6.0) mmHg before to 27.1 (+/- 12.1) mmHg during the procedure (P < 0.024). Concomitantly, mean SpO2 (+/- SD) also decreased from 99.9 (+/- 0.4)% before to 95.7 (+/- 11.1)% during the procedure (P < 0.015). P(etCO2) changes seemed to precede the variations in SpO2, especially in young patients who experienced significant desaturation and decompensation during FFB. We conclude that PetCO2 and SpO2 decrease during FFB in children, even with supplemental oxygen. We speculate that this reflects airway obstruction by the instrument. Further studies are needed to assess the utility of PetCO2 monitoring in pediatric FFB.

Adolescent↗

Ribavirin effect on pulmonary function in young infants with respiratory syncytial virus bronchiolitis.

To assess the effect of ribavirin on pulmonary function in infants with respiratory syncytial virus bronchiolitis, we performed a randomized (nonmatched), double blinded, placebo-controlled study of 19 infants with RSV bronchiolitis. Infants with underlying respiratory, cardiac or immunologic disease were excluded. Patients were given ribavirin (10) or placebo (9) via an aerosol generator for 18 hours/day for 3 days. Pulmonary function (dynamic compliance, total lung resistance) was calculated using a pneumotachographic method on Days 1, 2 and 7. Differences between groups on clinical criteria were not found. Approximately one-half of each group showed increased compliance and decreased lung resistance after 24 to 48 hours of therapy. By Day 7 compliance had increased 30% in the placebo group and 210% in the ribavirin-treated infants (P = 0.05). Significant differences in the rate of change of lung resistance were not seen by Day 7. We conclude that previously noted improvements in the early course of respiratory syncytial virus bronchiolitis treated with ribavirin do not appear to be a result of measurable changes in pulmonary function. However, paradoxical increases in airway resistance were not found in patients treated with ribavirin.

Aerosols↗

Cefepime. Pharmacokinetics and clinical response in patients with cystic fibrosis.

OBJECTIVE: To measure first-dose and steady-state plasma, urine, and sputum concentrations of cefepime and make preliminary assessments of the clinical efficacy of cefepime in patients with cystic fibrosis. DESIGN: Open noncomparative clinical trial. SETTING: Memorial Miller Children's Hospital of Long Beach, Calif. PARTICIPANTS: Twelve patients, aged 4 to 41 years, with a confirmed diagnosis of cystic fibrosis and chronic bronchopulmonary infections. INTERVENTIONS: Patients received cefepime at 50 mg/kg per dose (maximum dose, 2 g per dose) given intravenously every 8 hours. Clinical evaluations, pulmonary function tests, quantitative sputum cultures, and sensitivity testing were performed before, at the end of, and 2 weeks after therapy. MEASUREMENTS AND MAIN RESULTS: Mean (+/- SD) peak plasma concentrations after the first dose were 148.2 (36.6) mg/L; the following other values were included: half-life, 1.59 (0.46) hours; area under the curve, 292 (94) microgram/h per milliliter; total-body clearance, 3.01 (1.46) mL/min per kilogram; volume of distribution at steady state, 0.32 (0.10) L/kg; and percent of dose recovered in urine, 52% (27%). Steady-state and first-dose values were similar. Trough levels varied from 6.4 to 7.2 mg/L. Mean (+/- SD) sputum concentrations at steady state varied from 6.3 (5.4) to 4.8 (2.3) mg/L. At completion of therapy, nine of 10 patients' conditions were improved as indicated by clinical scores (greater than 10 points), forced vital capacity (greater than 10%), and a greater than or equal to 1 log decrease in sputum bacterial concentration. Cefepime was well tolerated in 10 patients, but rash and light-headedness developed in two patients. Pseudomonas aeruginosa minimum inhibitory concentration90 increased from the start (64 mg/L) to the end of therapy (256 mg/L) and was unchanged 2 weeks later. CONCLUSION: Based on these data and the potential advantage of a single agent for the treatment of mixed infections (Staphylococcus aureus and P aeruginosa), comparative clinical trials of cefepime and standard therapy for bronchopulmonary exacerbations in patients with cystic fibrosis appear to be warranted.

Adolescent↗

Detrimental effect of hypotonic cromolyn sodium.

In a randomized, double-blind, placebo-controlled, crossover study, inhalation of the commercially available nebulized form of cromolyn sodium resulted in a significant decrease in forced midexpiratory flow rate between the 25th and 75th percentile points, equivalent to that observed for distilled water, in children with chronic asthma. We conclude that inhalation of the current hypotonic concentration of cromolyn sodium may be detrimental.

Administration, Inhalation↗

Familial pulmonary nodular lymphoid hyperplasia.

We describe three persons in one family with diffuse lung infiltrates, digital clubbing, and chronic hypoxia. Elevated immunoglobulin levels and antinuclear antibodies were found in all patients; pathologic findings included hyperplastic lymphoid follicles infiltrating the epithelium of the small airways. These cases may represent a familial systemic autoimmune disorder seen primarily with pulmonary compromise.

Adult↗

Disseminated intravascular coagulation associated with Staphylococcus aureus septicemia is mediated by peptidoglycan-induced platelet aggregation.

Disseminated intravascular coagulation (DIC) may complicate severe septicemia caused by Staphylococcus aureus. S. aureus can induce spontaneous platelet aggregation in vitro, the rapidity and degree of which correlates with the severity of DIC in patients with sepsis. Purified peptidoglycan from DIC isolates aggregated human platelets in the presence of staphylococcal protein A with significantly shorter aggregation times than did peptidoglycan from non-DIC isolates. Purified teichoic acid from DIC and non-DIC isolates failed to aggregate platelets in vitro, or in vivo in guinea pigs but inhibited the peptidoglycan-induced aggregation in a dose-response manner. These studies suggest that peptidoglycan may mediate S. aureus-induced spontaneous platelet aggregation in vitro and DIC in vivo. The variability among strains of S. aureus to induce DIC and platelet aggregation may depend on the unique composition of their peptidoglycan and perhaps also the extent of exposure or availability of cell wall teichoic acid.

Animals↗

Characterization and regulation of beta 1-adrenergic receptors in a human neuroepithelioma cell line.

Intact human neuroepithelioma SK-N-MC cells bound the beta-adrenergic antagonist (-)-[3H]-CGP 12177 with a KD of 0.13 nM and a Bmax of 17,500 sites/cell. When the cells were exposed to beta-adrenergic agonists, they accumulated cyclic AMP in the following order of potency: isoproterenol much greater than norepinephrine greater than epinephrine, which is indicative of a beta 1-subtype receptor. Membranes prepared from the cells bound (-)-3-[125I]iodocyanopindolol with a KD of 11.5 pM. Inhibition of agonist-stimulated cyclic AMP production and competition binding experiments indicated that the beta 1-selective antagonists CGP 20712A and ICI 89,406 were much more potent than the beta 2-selective antagonist ICI 118,551. Analysis of the displacement curves indicated that the cells contained only beta 1-adrenergic receptors. Northern blot analysis of SK-N-MC mRNA using cDNA probes for the beta 1- and beta 2-adrenergic receptors revealed the presence of a very strong beta 1-adrenergic receptor mRNA signal, while under the same conditions no beta 2-adrenergic receptor mRNA was observed. Thus, SK-N-MC cells appear to express a pure population of beta 1-adrenergic receptors. When the cells were exposed to isoproterenol, there was no observable desensitization during the first hour. After longer exposure, desensitization slowly occurred and the receptors slowly down-regulated to 50% of control levels by 24 h. Other agents that elevate cyclic AMP levels, such as forskolin, cholera toxin, and cyclic AMP analogues, caused no or little substantial receptor loss.

Adrenergic beta-Antagonists↗

Femoral artery cannulation for monitoring in critically ill children: prospective study.

Seventy-seven attempted percutaneous femoral artery cannulations were prospectively evaluated in 74 children. Artery cannulation was successfully accomplished in 73 (95%) cases and lasted for a mean of 6 days. Sixty percent of the catheters were inserted on the first attempt. Fifty-two (71%) patients weighed less than 10 kg and 55 (75%) patients were less than 12 months old. Fifty-one (70%) patients received inotropic support at the time of cannulation, and 27 (37%) eventually died from causes unrelated to catheter insertion. There was one episode each of line-associated infection and transient distal ischemia not resulting in tissue loss, and two episodes of catheter malfunction. In eight (11%) patients, signs of distal vascular insufficiency developed shortly catheter placement and resolved after catheter removal. The development of this complication correlated significantly (p less than .05) with younger age (5.5 vs. 22.3 months). We conclude that femoral artery cannulation has a high degree of success in very small, critically ill children. It should be considered an acceptable alternative to small-vessel cannulation when the latter is not technically achievable, or in the unstable patient where rapid establishment of reliable arterial access is necessary.

Catheterization, Peripheral↗

Laryngomalacia in children.

Two hundred three (68 percent) of 297 children with laryngomalacia had associated respiratory disorders by flexible fiberoptic bronchoscopy (FFB). Associated disorders included congenital respiratory anomalies, a variety of anatomic obstructions of the upper and lower airways, and aspiration disorders. Mean age for isolated laryngomalacia (type 1) was 11.5 weeks (range, 5 weeks to 4 months) while children with laryngomalacia and associated respiratory disorders (type 2) had a mean age of 9.06 years (range, 6 weeks to 18 years). We conclude the following: (1) complete evaluation of the pediatric airways (bronchoscopy) is recommended in every symptomatic child with diagnosis of laryngomalacia confirmed by laryngoscopy; (2) type 1 laryngomalacia was more common in early infancy while type 2 laryngomalacia was associated with older age; (3) although type 2 laryngomalacia is the most common endoscopic diagnosis in our experience, the majority of cases were associated with lower airway dysfunction.

Adolescent↗

Dose-response relationship of inhaled metaproterenol sulfate in preschool children with mild asthma.

The dose-response relationship of single doses of nebulized metaproterenol sulfate 5% inhalant solution was evaluated by placebo-controlled, parallel-group study of 30 children, aged 3 to 6 years old, with stable asthma. Total respiratory resistance, the primary variable used to assess response, was measured by the forced oscillation method for a period of 6 hours from the start of inhalation. When comparisons were made between metaproterenol sulfate and saline, only 0.01 and 0.02 mL/kg showed significant bronchodilation (P less than .05) in percent change from baseline and area under the curve. However, no significant differences were seen between these doses. Moreover, the effect was sustained for 3 hours with both higher doses. Minimal side effects were observed. Metaproterenol sulfate 5% inhalant solution at a dose of 0.01 mL/kg seems to be optimal to elicit significant and sustained bronchodilatory response in preschool children with mild asthma.

Airway Resistance↗

Arteriotracheal fistula in patients treated for lymphoma.

Exsanguinating hemorrhage is an unusual cause of death in patients who are being treated for neoplasms. We report two cases of adolescents with mediastinal non-Hodgkin's lymphoma who each developed a fistula between the right brachiocephalic trunk and the trachea following mediastinal irradiation and systemic chemotherapy. During the hospital course, the patients had each suffered a respiratory arrest and undergone difficult endotracheal intubation. The tracheal ulcerations at the fistula sites were unsuspected prior to autopsy.

Adolescent↗

Early onset of childhood pulmonary lymphangiomyomatosis.

The authors present the first case of lymphangiomyomatosis in a pediatric patient. Radiographic findings, biopsy, computerized tomography, and electron microscopy were useful in detailing the presentation of early onset of pulmonary lymphangiomyomatosis. The unusual presentation of this child includes a description of her disease prior to any pulmonary symptomatology and 4 years of follow-up.

Biopsy↗

Pentobarbital therapy does not improve neurologic outcome in nearly drowned, flaccid-comatose children.

The effect of pentobarbital therapy was studied prospectively in 31 nearly drowned children in a flaccid state of coma. Each child was assigned to one of two sequential treatment groups. Group A: 16 children were treated with hypothermia and IV pentobarbital, achieving serum levels greater than 25 mu/mL within 48 hours of admission. Group B: 15 children were treated with hypothermia but no pentobarbital. All patients received "conventional therapy" (ie, PaCO2 20 to 25 mm Hg, PaO2 90 to 100 mm Hg, fluid restriction, pancuronium bromide, and furosemide or mannitol). Analysis of variance failed to detect differences for age, estimated time of submersion, arterial pH, core temperature, and mean intracranial pressure between the patients prior to treatment with pentobarbital. In Group A, six patients (37%) recovered completely and were neurologically intact, six patients (37%) had severe brain damage and four patients (26%) died. In Group B, six patients (40%) recovered completely, six patients (40%) survived with brain damage, and three patients (20%) died. There were no statistical differences between the two groups (P greater than .05, chi 2 analysis) for the mortality rate, survival with brain damage, and complete recovery. The results suggest that: (1) pentobarbital therapy does not improve neurologic outcome for nearly drowned, flaccid-comatose children; (2) previous claims implying better outcome with hypothermia combined with pentobarbital therapy may be attributed to the effect of hypothermia alone; and (3) pentobarbital therapy may not be justified in nearly drowned, flaccid-comatose victims.

Brain Damage, Chronic↗

Association of lipid-laden alveolar macrophages and gastroesophageal reflux in children.

The association of lipid-laden alveolar macrophages (LLAM) and gastroesophageal reflux (GER) was investigated prospectively in 115 patients in two groups. Group 1 included 74 children with chronic respiratory tract disorders and documented GER by prolonged esophageal pH monitoring, barium esophagram, and esophagoscopy; group 2 included 41 children with chronic respiratory tract disorders without GER. LLAM were present in 63 (85%) and eight (19%) children from groups 1 and 2, respectively (P less than 0.0001). Thus a strong association between the presence of LLAM and GER in children with chronic respiratory tract disorders was established. We suggest that LLAM from bronchial lavage may be a useful marker for tracheal aspiration in children with GER in whom chronic lung disease may subsequently develop.

Child↗

In vitro correlation of platelet aggregation with occurrence of disseminated intravascular coagulation and subacute bacterial endocarditis.

Platelet-bacterial interactions were examined in vitro by incubating organisms isolated from patients with septicemia with normal platelet-rich plasma. The potency of various species of gram-positive and gram-negative bacteria to induce irreversible platelet aggregation was then determined in an aggregometer. The aggregation curves produced by the bacteria resembled the normal platelet response to collagen and were impeded by the presence of aspirin. Strains of Staphylococcus aureus and Pseudomonas aeruginosa isolated from 25 different patients produced maximum increases in light transmission and irreversible platelet aggregation with relatively rapid mean aggregation times; six of these patients had clinical and laboratory evidence of disseminated intravascular coagulation. In contrast, isolates of alpha streptococcus and Staphylococcus epidermidis induced irreversible platelet aggregation much less commonly and were associated with considerably longer mean aggregation times. None of the latter group of patients had evidence of disseminated intravascular coagulation. Isolates of bacteria from a small number of patients with subacute bacterial endocarditis uniformly induced irreversible platelet aggregation. Addition of paired bacterial isolates to normal platelet-rich plasma demonstrated a synergistic aggregation response. These data suggest that a relative hierarchy exists in bacterial strain potency to induce irreversible platelet aggregation. The rapidity and degree of aggregation in vitro correlated well with the clinical and laboratory evidence for subacute bacterial endocarditis and disseminated intravascular coagulation in vivo. These observations may provide useful adjunctive laboratory information to help establish the diagnosis of subacute bacterial endocarditis, especially in the clinical setting where the classical findings of endocarditis are not obvious during initial presentation.

Blood Platelets↗