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Biomedical subjects

L R Frankel

Publications and source records attributed to L R Frankel.

At least 19 recordsLinked to original sources
PubMed2001

Human alveolar macrophages induce functional inactivation in antigen-specific CD4 T cells.

BACKGROUND: Alveolar macrophages (AMCs) are the most abundant phagocytic cells in the lung, but they present antigen poorly to T cells. OBJECTIVES: The objectives of our studies were to more clearly define the mechanisms by which AMCs present antigen to T cells and to determine whether AMCs actively inhibit T-cell activation. METHODS: We studied purified human CD4 T cells and compared the capacity of allogeneic AMCs and peripheral blood monocytes to induce T-cell proliferation and cytokine production. RESULTS: We previously demonstrated that human AMCs fail to upregulate expression of B7-1 and B7-2 on stimulation with IFN-gamma. We now demonstrate that AMCs actively induce T-cell unresponsiveness (functional inactivation) in an antigen-specific manner and reduce the capacity of CD4 T cells to respond on secondary stimulation. The induction of unresponsiveness was reversed by the addition of CD28 costimulation or IL-2. However, interruption of Fas/Fas ligand interactions or of B7/CTLA-4 interactions did not prevent unresponsiveness, indicating that neither CTLA-4 triggering nor Fas-induced apoptosis was involved in the induction of T-cell unresponsiveness. CONCLUSIONS: These studies indicate that AMCs actively tolerize CD4 T cells in an antigen-specific fashion. We propose that AMCs mediate a form of immune privilege in the lungs that effectively limits immune responses in the pulmonary compartment but has little effect on systemic immunity.

Abatacept↗
PubMed2001

Group A streptococcal meningitis: report of a case and review of literature since 1976.

Group A streptococcal (GAS) invasive disease has become increasingly common in recent years. However, acute bacterial meningitis caused by this pathogen is unusual. We report a case of GAS meningitis in a previously healthy 21/2-year-old child associated with a dramatically rapid course and fatal outcome. A literature review of previously reported cases is presented. This case serves as a reminder that GAS can cause severe meningitis in otherwise healthy hosts.

Adolescent↗
PubMed1997

The need for inotropic support in a subgroup of infants with severe life-threatening respiratory syncytial viral infection.

BACKGROUND: We experienced an unusual complication of life-threatening respiratory syncytial viral disease cardiovascular compromise. Life-threatening respiratory syncytial virus (RSV) infection has predominancy involved with ventilatory support for respiratory distress and/or failure. We performed a retrospective chart review of 20 consecutive infants admitted to the pediatric intensive care unit (PICU) for impending respiratory failure. METHODS: Seventeen required ventilatory support. As part of the infants' initial assessment, blood pressure, distal perfusion [capillary refill time (CRT) > or = 3 sec], decreased peripheral pulses, and peripheral mottling were used to determine cardiovascular compromise. These infants received volume resuscitation either at the referring facility or the PICU until euvolemia was obtained, as determined by central venous pressure (CVP) monitoring (between 3 to 7 cm H20). Nine of the 20 infants did not respond to volume resuscitation alone and required vasopressor support in the form of: Dopamine (7 patients, 5-10 micrograms/kg/min), Dobutamine (2 patients, 5-7 micrograms/kg/min), and one who expired required both Epinephrine (600 ng/kg/min) and Dopamine (10 micrograms/kg/min). The mean ages of these 9 patients were 6.2 +/- 3.4 weeks (range 3-12 weeks), the mean duration of ventilation was 7.2 +/- 4.1 days (range 4-12 days). The mean duration of pharmacologic support was 69.7 +/- 47 hours (range 14-168 hours). The mean ages of RSV+ infants not requiring inotropic support was 19.4 +/- 27.4 weeks (range 1-90 weeks), and mean duration of ventilation was 5.5 +/- 5.9 days (range 2-20 days). RESULTS: The inotrope treated patients were weaned from pharmacologic support prior to extubation, without any hemodynamic deficits. Our experience with this rather high incidence of hemodynamic complications during this RSV epidemic was unexpected. CONCLUSION: These results substantiate the fact that younger patients with RSV disease are at both greater risk for pulmonary complications and cardiovascular deterioration and may thus benefit from pharmacologic support.

Cardiotonic Agents↗
PubMed1996

Identifying early predictors of mortality in pediatric patients with acute leukemia and pneumonia.

STUDY OBJECTIVE: To identify clinical variables of pneumonia in children with acute leukemia that predicted respiratory failure and mortality. DESIGN: A retrospective chart review of children with acute leukemia admitted to the hospital with the diagnosis of pneumonia or ARDS from March 1991 to April 1994. SETTING: Lucile Salter Packard Children's Hospital at Stanford, a 168-bed teaching hospital and regional tertiary referral center for children in northern California. PATIENTS: During this study period, 20% of the 174 admissions of children with acute leukemia had pneumonia at the time of admission or during the course of the hospitalization for a total of 36 admissions. The mean age of these children was 9.2 +/- 1.1 years. RESULTS: Eleven percent of the children with pulmonary infiltrates in one quadrant on the chest x-ray film at the onset of pneumonia and 53% of the children with pulmonary infiltrates in more than one quadrant at the onset of pneumonia died. Fifteen percent of the children without sepsis at the onset of pneumonia and 70% of the children with sepsis at onset died. Eighteen percent of the children without shock at the onset of pneumonia and 75% of the children with shock at the onset died. None of the children died who required < or = 3L/min of O2 to maintain SO2 > or = 95%, but 79% of the children who required > 3L/min O2 died. Using the criteria "> 3 L/min O2 by nasal cannula to maintain SO2 > or = 95%" to identify the nonsurvivors had a sensitivity of 100% and specificity of 88%. This specificity was not increased by combining the criteria "O2 requirements at any time" and "the extent of pulmonary infiltrates at the onset of pneumonia." All children who required mechanical ventilatory support for respiratory failure had previously received > 3 L/min O2 by nasal cannula to maintain SO2 > or = 95% for 37.8 +/- 12.9 h (range 3 to 96 h). Nine of the 10 children in our study who received mechanical ventilation died. CONCLUSION: In children with acute leukemia and pneumonia, the amount of O2 required to maintain SO2 > or = 95% may identify those who are likely to develop respiratory failure hours before mechanical ventilatory support is needed. The ability to identify children at risk for respiratory failure is not increased by combining the risk factors "oxygen requirements" and "extent of pulmonary infiltrates at the onset of pneumonia". Finally, only 10% of the children who required mechanical ventilatory support survived.

Bone Marrow Transplantation↗
PubMed1995

Venous catheter thrombus formation and pulmonary embolism in children.

Central venous catheter (CVC)-related thrombus formation has been increasingly recognized as a complication in adults and somewhat less frequently in children and neonates. However, the association of CVC thrombus and pulmonary embolism (PE) has rarely been reported in infants or children, and the few existing reports primarily involve chronic, indwelling CVCs such as Broviac or Hickman catheters. During an 18-month-period of autopsy review, we found that 5 of our pediatric intensive care unit patients had autopsy-proven CVC thrombus and pulmonary embolism. All of them had prolonged mechanical ventilation for respiratory failure and required insertion of one or more short-term, temporary CVCs during the course of routine critical care management. In retrospect, signs related to CVC thrombus were present in 4 patients (3 had positive blood cultures and 1 had persistent hypertension). PE was not diagnosed until autopsy in every case. The diagnosis may have been missed because the symptoms of PE are the same as those of severe lung disease. We, therefore, advocate a heightened suspicion of CVC thrombus formation and PE in critically ill children with respiratory failure and temporary CVCs and recommend early diagnostic ultrasound to confirm the diagnosis. Once a CVC thrombus is found, subsequent pulmonary deterioration may necessitate evaluation for acute PE.

Catheterization, Central Venous↗
PubMed1995

Cardiac transplantation for hypertrophic cardiomyopathy associated with Sengers syndrome.

Sengers' syndrome is a rare condition consisting of congenital cataracts, mitochondrial myopathy, and hypertrophic cardiomyopathy. The syndrome is transmitted in an autosomal recessive pattern. Progressive cardiac failure is the cause of death in most patients. This report describes cardiac transplantation for the treatment of the cardiomyopathy associated with Sengers' syndrome.

Cardiomyopathy, Hypertrophic↗
PubMed1995

Human alveolar macrophages present antigen ineffectively due to defective expression of B7 costimulatory cell surface molecules.

Alveolar macrophages, resident phagocytic cells in the lung that derive from peripheral blood monocytes, are paradoxically ineffective in presenting antigen to T cells. We found that antigen presentation by alveolar macrophages could be restored by the addition of anti-CD28 mAb to cultures of T cells and macrophages, indicating that costimulation by alveolar macrophages via the CD28 pathway was defective. In addition, we found that alveolar macrophages activated with IFN-gamma failed to express B7-1 or B7-2 antigens, which normally ligate CD28 on T cells and provide a costimulatory signal required for the activation of T cells. These observations are the first to demonstrate the inability of a "professional" antigen-presenting cell type to effectively express the costimulatory molecules B7-1 and B7-2. Inasmuch as immune reactions within the lung are inevitably associated with inflammatory injury to pulmonary tissue, these observations suggest that reduced expression of B7-1 and B7-2 by alveolar macrophages may be advantageous, as a critical mechanism involved in the induction of peripheral tolerance to the abundance of antigens to which mucosal tissues are continuously exposed.

Adult↗
PubMed1993

High-frequency jet ventilation in children with the adult respiratory distress syndrome complicated by pulmonary barotrauma.

High-frequency jet ventilation (HFJV) was used in 29 children with severe ARDS complicated by pulmonary barotrauma (PBT). Treatment with HFJV was begun when PBT was progressing over a 24-h period while receiving conventional ventilation (CV). The mean (+/- SD) age was 0.95 +/- 1.21 years (range, 0.03-4 years). The most common diagnosis was viral pneumonia (n = 17); other diagnoses included aspiration pneumonitis (n = 4), bacterial pneumonia (n = 3), multiple trauma (n = 2), and near-drowning (n = 3). The Bunnell Life-Pulse ventilator was used at a rate of 240/min or 300/min, with inspiratory time of 0.02 sec. Twenty children survived (69%). Survivors and nonsurvivors had equal disease severity prior to HFJV as assessed by ventilator settings, alveolar-to-arterial oxygen tension gradient, oxygenation index, and blood gas values. Survivors had spent significantly less time on conventional ventilation prior to HFJV than nonsurvivors, with a mean (+/- SD) of 3.7 +/- 2.1 days vs 9.6 +/- 4.5 days, respectively (P < 0.05). Survivors underwent an average of 4.4 +/- 3.9 days of HFJV, which supported adequate gas exchange with lower airway pressures, and produced resolution or significant improvement in airleak on chest radiograph. In conclusion, we speculate that the application of HFJV early in the course of severe hypoxemic respiratory failure complicated by airleak, allows the reduction of airway pressures, thereby minimizing pulmonary barotrauma and allowing the lung to recover from the underlying insult. Further controlled evaluation of HFJV in this high risk group of patients is warranted.

Child, Preschool↗
PubMed1991

A controlled trial of aerosolized ribavirin in infants receiving mechanical ventilation for severe respiratory syncytial virus infection.

BACKGROUND: Although the antiviral agent ribavirin improves the course of lower respiratory tract disease in spontaneously breathing infants with respiratory syncytial virus infection, it is not known whether ribavirin can benefit infants with severe respiratory syncytial virus disease who require mechanical ventilation. METHODS: We conducted a randomized, double-blind, placebo-controlled evaluation of ribavirin (20 mg per milliliter) administered continuously in aerosolized form to infants receiving mechanical ventilation for respiratory failure that was caused by documented respiratory syncytial virus infection. RESULTS: Of the 28 infants (mean [+/- SD] age, 1.4 +/- 1.7 months) enrolled, 7 had underlying diseases predisposing them to severe infection (mean age, 3.0 +/- 2.6 months), and 21 were previously normal (mean age, 0.8 +/- 0.9 month). Among the 14 infants who received ribavirin, the mean duration of mechanical ventilation was 4.9 days (as compared with 9.9 days among the 14 who received placebo; P = 0.01), and the mean length of supplemental oxygen use was 8.7 days (as compared with 13.5 days; P = 0.01). The mean length of the hospital stay was 13.3 days after treatment with ribavirin and 15.0 with placebo (P = 0.04). When only the 21 previously normal infants were considered, the mean length of the hospital stay was 9.0 days for the ribavirin recipients and 15.3 days for those who received placebo (P = 0.005). CONCLUSIONS: In infants who require mechanical ventilation because of severe respiratory syncytial virus infection, treatment with aerosolized ribavirin decreases the duration of mechanical ventilation, oxygen treatment, and the hospital stay.

Aerosols↗
PubMed1989

Severe metabolic acidosis after acute naproxen sodium ingestion.

Naproxen, a nonsteroidal anti-inflammatory drug (NSAID), is a propionic acid derivative that possesses analgesic and antipyretic properties through inhibition of prostaglandin synthesis. The propionic acids have been considered the least toxic of the NSAIDs, and one, ibuprofen, is currently available as an over-the-counter medication. Though acidosis has been reported with ibuprofen, no such occurrence has been reported for naproxen sodium. We report the case of a 15-year-old girl who presented with severe metabolic acidosis and seizures that rapidly followed naproxen sodium ingestion. Serum bicarbonate levels returned to normal 12 hours after admission and correlated with the known pharmacokinetics of naproxen. The pharmacokinetics of naproxen and treatment of its overdose, and possible mechanisms of metabolic acidosis are reviewed.

Acidosis↗
PubMed1988

Retinal folds in the shaken baby syndrome.

We examined two children with presumed shaken baby syndrome. Both children suffered severe, indirect closed head trauma with intracranial hemorrhage, sharply increased intracranial pressure, and extensive neurologic damage. In addition to extensive retinal and preretinal hemorrhages, bilateral symmetric white ring-shaped retinal folds were seen encircling the macula outside the vascular arcades. These retinal folds may be a hallmark of shaking injuries in child abuse victims.

Child Abuse↗
PubMed1988

Dissociation of mean airway pressure and lung volume during high-frequency oscillatory ventilation.

Eight kittens were studied during high-frequency oscillatory ventilation (HFOV) using an airway vibrator. HFOV was performed at 1000 and 1800 cycle/min at three present oscillatory amplitude settings and with lungs normal and injured by saline lavage. Change in lung volume (LV) during HFOV was compared to change in LV obtained during static inflation at matched mean airway pressure (Paw) of 5, 10, 15 and 20 cm H2O. LV during HFOV was significantly higher than during static inflation, and increased as oscillatory amplitude increased. LV was significantly lower after lung injury for matched HFOV settings, and was not affected by rate. Dissociation of Paw and LV during HFOV is observed implying that mean alveolar pressure (Palv) exceeds Paw during HFOV in this experimental model. The safe clinical application of HFOV may involve measurement of Palv or LV.

Airway Resistance↗
PubMed1988

Bronchoalveolar lavage for diagnosis of pneumonia in the immunocompromised child.

Seven children with immunocompromised states were referred to the pediatric bronchoscopy service for evaluation of pneumonia. Flexible fiberoptic bronchoscopy accompanied with bronchoalveolar lavage was performed in all seven of these children. A definitive diagnosis was made for six of these seven patients. The diagnosis included Pneumocystis carinii in three, Candida albicans in two, and cytomegalovirus in one. There were no complications associated with the procedure. Flexible fiberoptic bronchoscopy with bronchoalveolar lavage should be considered early in the evaluation of the immunocompromised child with pneumonia.

Adolescent↗
PubMed1987

A technique for the administration of ribavirin to mechanically ventilated infants with severe respiratory syncytial virus infection.

Fifteen infants with respiratory syncytial virus pulmonary infection admitted to our pediatric ICU from December 1, 1985 through April 30, 1986, required mechanical ventilation. These patients were placed on an open trial of ribavirin therapy. We describe a technique for the safe delivery of aerosolized ribavirin to these infants while on the ventilator. The agent was delivered for 16 h/day for 7 days. Modifications of the ventilator circuit were needed to prevent the condensation of the drug in the ventilator tubing and to allow for the safe and effective operation of the ventilator. A common ventilator strategy was used for all patients. The highest positive inspiratory pressure generated was 42 +/- 9.5 (SD) cm H2O, the highest PEEP was 5.9 +/- 3.2 cm H2O, the duration of ventilation was 10.7 +/- 8.5 days, and exposure to fraction of inspired oxygen was greater than or equal to 0.6 for 55.3 h. Ribavirin levels were measurable in two patients, thereby demonstrating that the drug was in fact delivered and absorbed. Our preliminary results demonstrate that ribavirin can be delivered to the patients with respiratory syncytial viral infections who require mechanical ventilation; however, further studies are indicated to evaluate the efficacy and dose responsiveness, alterations in pulmonary dynamics, and safety of ribavirin in delivery to infants requiring ventilation.

Administration, Inhalation↗