Biomedical subjects

P Silver

Publications and source records attributed to P Silver.

At least 37 records · Page 2Linked to original sources

PubMed1997

The impact of gender on outcome from mechanical ventilation.

OBJECTIVE: To determine the relation of gender to outcome for patients requiring mechanical ventilation. DESIGN: A prospective cohort study. SETTING: Medical and surgical ICUs in two university-affiliated teaching hospitals. PATIENTS: Three hundred fifty-seven patients requiring mechanical ventilation. INTERVENTIONS: Prospective patient surveillance and data collection. MEASUREMENTS AND RESULTS: The primary outcome measure was hospital mortality. Secondary outcome measures included need for reintubation, hospital and ICU length of stay, duration of mechanical ventilation, and hospital charges. The hospital mortality rate for women (n = 189) was significantly greater than the hospital mortality rate for men (n = 168) (28.0% vs 17.3%; p = 0.016). This difference in hospital mortality was observed despite similar baseline demographic characteristics, severity of illness, indications for mechanical ventilation, and number of dysfunctional organ systems in these two groups of patients. The duration of mechanical ventilation and ICU length of stay was also significantly longer for female patients compared with male patients (p < or = 0.056). In a logistic-regression analysis, female gender was found to be independently associated with hospital mortality (adjusted odds ratio [AOR] = 2.38; 95% confidence interval [CI] = 1.70 to 3.35; p = 0.010). The presence of ARDS (AOR = 10.69; 95% CI = 5.86 to 19.51; p < 0.001), the number of dysfunctional organ systems (AOR = 2.07; 95% CI = 1.78 to 2.41; p < 0.001), Acute Physiology and Chronic Health Evaluation (APACHE) II predicted mortality (AOR = 1.15; 95% CI = 1.11 to 1.19; p < 0.001), and patient age (AOR = 1.04; 95% CI = 1.03 to 1.06; p < 0.001) were also found to be independently associated with hospital mortality. The number of dysfunctional organ systems present at the start of mechanical ventilation was the major independent predictor of hospital mortality (54% of total explanatory power). Patient gender was the least important independent predictor of hospital mortality (5% of total explanatory power). CONCLUSIONS: In this patient cohort, women requiring mechanical ventilation were at greater risk for hospital mortality than men. Physicians should be aware that outcome differences according to gender can occur when evaluating or designing clinical trials involving mechanically ventilated patients. Future studies are necessary to determine the general applicability of these findings and to identify explanations for such observed gender-specific differences in outcome.

APACHE↗

PubMed1997

Patient transport from intensive care increases the risk of developing ventilator-associated pneumonia.

STUDY OBJECTIVE: To determine whether patient transport out of the ICU is associated with an increased risk of developing ventilator-associated pneumonia. DESIGN: Prospective cohort study. SETTING: ICUs of Barnes-Jewish Hospital, a university-affiliated teaching hospital. PATIENTS: Five hundred twenty-one ICU patients requiring mechanical ventilation for > 12 h. INTERVENTION: Prospective patient surveillance and data collection. MEASUREMENTS AND RESULTS: The primary outcome measure was the development of ventilator-associated pneumonia. A total of 273 (52.4%) mechanically ventilated patients required at least one transport out of the ICU while 248 (47.6%) patients did not undergo transport. Sixty-six (24.2%) of the transported patients developed ventilator-associated pneumonia compared with 11 (4.4%) patients in the group not undergoing transport (relative risk=5.5; 95% confidence interval [CI]=2.9 to 10.1; p<0.001). Multiple logistic regression analysis demonstrated that a preceding episode of transport out of the ICU was independently associated with the development of ventilator-associated pneumonia (adjusted odds ratio=3.8; 95% CI=2.6 to 5.5; p<0.001). Other variables independently associated with the development of ventilator-associated pneumonia included reintubation, presence of a tracheostomy, administration of aerosols, and male gender. CONCLUSIONS: We conclude that patient transport out of the ICU is associated with an increased risk for the development of ventilator-associated pneumonia.

APACHE↗

PubMed1996

Genetic analysis of macromolecular transport across the nuclear envelope.

Numerous factors that promote movement of macromolecules in and out of the nucleus have now been identified. These include both soluble cytoplasmic and nucleoplasmic proteins and proteins of the nuclear pore complex (NPC). Genetic analyses of the nuclear transport process in the model organism, the budding yeast Saccharomyces cerevisiae, have revealed remarkable conservation of all of these factors. In addition, important clues as to how these factors promote the unique bidirectional movement across the NPC have emerged from studies of yeast. We summarize the characterization and genetic interactions of the soluble transport factors and present data to illustrate how genetic experiments can be used to further define the import and export pathways.

Biological Transport, Active↗

PubMed1996

A simplified, competitive RT-PCR method for measuring rat IFN-gamma mRNA expression.

We describe an adaptation of competitive RT-PCR to quantitate rat IFN-gamma mRNA expression. An IFN-gamma DNA mimic that shared the same primers and had an identical sequence to the target mRNA except for deletion of 66 nucleotides was created by a simple PCR amplification from target cDNA. To reduce variations of initial RNA concentrations, beta-actin cDNAs from each target RNA sample were normalized using the densitometric data. A known amount of pretitrated DNA competitor was then used to analyze the relative levels of target cDNA in different samples by PCR co-amplification. The amplification efficiency for both target and competitor remained constant throughout the PCR reaction, and the ratio of target to competitor PCR product remained proportional to the initial ratio of target to competitor. Relative mRNA levels among samples determined by this method were comparable to levels determined by northern blot analysis. They were also comparable to levels of IFN-gamma protein estimated by ELISA. We conclude that this method can be used to estimate the relative abundance of the target mRNA. This method is adaptable to quantitation of other cytokines and is particularly valuable if there are numerous samples or if the amount of initial mRNA is limited.

Animals↗

PubMed1996

Establishment and characterization of a murine CD4+ T cell line and clone that induce experimental autoimmune uveoretinitis in B10.A mice.

B10.A mice develop experimental autoimmune uveoretinitis after active immunization with the interphotoreceptor retinoid-binding protein (IRBP). CD4+ T cells play an important role in the development of the disease. In this study we have isolated and characterized a CD4+ T cell line and a T cell clone that induce experimental autoimmune uveoretinitis when transferred into naive B10.A mice. The cell line was isolated from draining lymph nodes of IRBP-immunized animals by repeated cycles of IRBP stimulation. The line was shown to be pathogenic after 4 rounds of in vitro stimulation with IRBP at 5 x 10(6) cells/mouse. A T cell clone derived from this line by limiting dilution was shown to be pathogenic when the same number of cells was injected; incidence and severity of disease, however, were much lower. After 16 rounds of IRBP-specific stimulation the cell line was pathogenic at 10(5) cells/mouse. Analysis of the V beta repertoire revealed that at this point the line was mostly composed of V beta 8.2- and V beta 6-positive cells (> 80% of the population). The uveitogenic clone expressed V beta 8.2. Both the T cell line and the clone elaborated an unrestricted lymphokine profile in vitro. However, when these cells were adoptively transferred into naive recipients, mRNA isolated from the uveitic retina showed only Th1 type cytokines. These data help to characterize the nature of pathogenic cells involved in ocular autoimmunity.

Animals↗

PubMed1996

The effect of mannitol on intracranial pressure in relation to serum osmolality in a cat model of cerebral edema.

OBJECTIVE: To determine whether intravenous mannitol administration reduces intracranial pressure (ICP) in a cat model of brain edema by changing serum osmolality. DESIGN: Prospective, controlled study. SETTING: Pediatric intensive care unit laboratory in a university hospital. INTERVENTIONS: Intraparenchymal ICP monitors were placed in 12 adult cats which subsequently underwent 60 min of continuous arteriovenous hemofiltration with countercurrent dialysis (CAVH-D), using sterile water with potassium chloride as a dialysate. The ultrafiltrate was replaced with a hypotonic solution causing a rapid reduction in serum osmolality while maintaining a euvolemic state. In six cats (control group) no further interventions were instituted, while in the six other cats (mannitol group) 1g/kg mannitol was administered intravenously immediately after CAVH-D had been discontinued. ICP was monitored continuously, and serum osmolality was determined at 15-min intervals during CAVH-D and for 30 min thereafter. RESULTS: ICP increased significantly in both the control and mannitol groups during 60 min of CAVH-D. After CAVH-D, ICP was reduced in the mannitol group while ICP remained significantly higher in the control group. An inverse linear correlation was demonstrated between serum osmolality and ICP values in the control group throughout the experiment, as well as during the first 60 min in the mannitol group. However, no such correlation existed in the mannitol group after mannitol administration, as no significant changes in serum osmolality were observed while a marked reduction in ICP values occurred. CONCLUSION: Mannitol is effective in reducing increased ICP in this model of euvolemic brain edema. However, 15 min after mannitol administration, no relationship between a continued decrease in ICP and a change in serum osmolality could be established. We postulate that the beneficial effect on ICP by mannitol outlasts its possible instantaneous and short-lived effect on serum osmolality.

Animals↗

PubMed1996

Albumin bolus administration versus continuous infusion in critically ill hypoalbuminemic pediatric patients.

OBJECTIVE: To test the hypothesis that the rate of degradation of exogenously administered albumin is faster with bolus administration than with continuous infusion and thus that a bolus administration is less efficacious in restoring blood albumin concentration (BAC) in the hypoalbuminemic critically ill pediatric patient. DESIGN: A prospective, controlled study of two groups of patients. SETTING: Pediatric intensive care unit (PICU) of a children's hospital. PATIENTS: 37 critically ill hypoalbuminemic patients (BAC < or = 2.8 g/dl), in whom no overt protein-losing disease was identified, were divided into two treatment groups and included in a 60-h study. INTERVENTIONS: 18 patients were given an i.v. bolus of 1 g/kg of 25% albumin over 4 h. This treatment was repeated after 24 and 48 h. Nineteen other patients were given the same dose of 1 g/kg of 25% albumin as a continuous 24-h infusion throughout the 60-h study period. BAC along with sodium, potassium, and total and ionized calcium were measured in the serum of blood samples obtained at predetermined intervals. MEASUREMENTS AND MAIN RESULTS: A 4 h bolus of albumin resulted in an acute rise in BAC, which declined to baseline within 24 h. A continuous infusion resulted in a steady rise in BAC with 24-h levels significantly higher than baseline. The percent change in mean BAC from baseline, calculated at 12-h intervals during the 60-h study period, showed a steady increase in the continuous infusion group with a 34% increase after the first 24 h. In contrast, the 4-h bolus method resulted in major fluctuations in the BAC values with only a 14% increase (p < 0.05) after 24 h. Albumin's volume of distribution, half-life and elimination constant, calculated based on blood albumin values during the first 24 h after the bolus administration, were 0.12 +/- 0.03 l/kg, 4.6 +/- 1.8 h and 0.17 +/- 0.06 h-1, respectively. This half-life did not apply to the continuous infusion group as a steady state was not achieved after 30 h (6 half-lives), and BAC continued to rise throughout the 60-h study period. No significant changes in blood electrolytes were observed with either method. CONCLUSIONS: The half-life of exogenous albumin in the critically ill hypoalbuminemic pediatric patient is short if given as a bolus. Continuous infusion therapy appears to be more efficacious in increasing BAC over time, as the half-life with this method appears to be longer.

Adolescent↗

PubMed1996

Continuous infusion of ketamine in mechanically ventilated children with refractory bronchospasm.

OBJECTIVE: To determine whether ketamine infusion to mechanically ventilated children with refractory bronchospasm is beneficial. DESIGN: Retrospective chart review. SETTING: Pediatric intensive care unit (PICU) of a children's hospital. PATIENTS: Seventeen patients, ages ranging from 5 months to 17 years (mean 6 +/- 5.7 years), were admitted to our PICU over a 3-year period and received ketamine infusion during a course of mechanical ventilation. The patients had acute respiratory failure associated with severe bronchospasm due to status asthmaticus (n = 11), bronchiolitis caused by respiratory syncytial virus (n = 4), and bacterial pneumonia (n = 2). INTERVENTIONS: All patients had been mechanically ventilated for 1-5 days (2.2 +/- 1.5 days) and received conventional treatment to relieve bronchospasm for more than 24 h prior to the initiation of ketamine treatment. An intravenous bolus of ketamine of 2 mg/kg, followed by continuous infusions of 20-60 micrograms/kg per minute (32 +/- 10 micrograms/kg per minute) was administered to all patients without changing their preexisting bronchodilatory regimen. Benzodiazepines were also given intravenously to all patients during the ketamine treatment. MEASUREMENTS AND MAIN RESULTS: The PaO2/FIO2 ratio in all patients (n = 17) and the dynamic compliance in the volume-preset mechanically ventilated patients (n = 12) were calculated. The PaO2/FIO2 ratio increased significantly from 116 +/- 55 before ketamine, to 174 +/- 82, 269 +/- 151, and 248 +/- 124 at 1, 8, and 24 h respectively, after the initiation of the ketamine infusion (p < 0.0001). Dynamic compliance increased from 5.78 +/- 2.8 cm3/cmH2O to 7.05 +/- 3.39, 7.29 +/- 3.37, and 8.58 +/- 3.69, respectively (p < 0.0001). PaCO2 and peak inspiratory pressure followed a similar trend of improvement with ketamine administration. The mean duration of the ketamine infusion was 40 +/- 31 h. One patient required glycopyrrolate 0.4 mg/day to control excessive airway secretions and one patient required an additional dose of diazepam to control hallucinations while emerging from ketamine. All patients were successfully weaned from mechanical ventilation and discharged from the PICU. CONCLUSION: Continuous infusion of ketamine to mechanically ventilated patients with refractory bronchospasm significantly improves gas exchange and dynamic compliance of the chest.

Adolescent↗

PubMed1996

SEC3 mutations are synthetically lethal with profilin mutations and cause defects in diploid-specific bud-site selection.

Replacement of the wild-type yeast profilin gene (PFY1) with a mutated form (pfy1-111) that has codon 72 changed to encode glutamate rather than arginine results in defects similar to, but less severe than, those that result from complete deletion of the profilin gene. We have used a colony color-sectoring assay to identify mutations that cause pfy1-111, but not wild-type, cells to be inviable. These profilin synthetic lethal (psl) mutations result in various degrees of abnormal growth, morphology, and temperature sensitivity in PFY1 cells. We have examined psl1 strains in the most detail. Interestingly, these strains display a diploid-specific defect in bud-site selection; haploid strains bud normally, while homozygous diploid strains show a dramatic increase in random budding. We discovered that PSL1 is the late secretory gene, SEC3, and have found that mutations in several other late secretory genes are also synthetically lethal with pfy1-111. Our results are likely to reflect an interdependence between the actin cytoskeleton and secretory processes in directing cell polarity and growth. Moreover, they indicate that the secretory pathway is especially crucial for maintaining budding polarity in diploids.

Actins↗

PubMed1996

Respiratory failure from corn starch aspiration: a hazard of diaper changing.

Corn starch powder is widely used for routine infant skin care as a substitute for talcum powder, as it is believed to have fewer respiratory hazards. We describe a one-month-old infant who presented to an emergency department with respiratory failure and a severe pneumonitis from aspiration of corn starch powder. The patient recovered after five days of mechanical ventilatory support. We conclude that careless use of corn starch for infant skin care can lead to accidental aspiration of this substance and severe respiratory disease.

Anti-Bacterial Agents↗

PubMed1996

Spiral computed tomographic scanning of the chest with three dimensional imaging in the diagnosis and management of paediatric intrathoracic airway obstruction.

BACKGROUND: The usefulness of spiral computed tomographic (CT) scans of the chest with three dimensional imaging (3D-CT) of intrathoracic structures in the diagnosis and management of paediatric intrathoracic airway obstruction was assessed. METHODS: A retrospective review was made of five consecutive cases (age range six months to four years) admitted to the paediatric intensive care unit and paediatric radiology division of a tertiary care children's hospital with severe respiratory decompensation suspected of being caused by intrathoracic large airway obstruction. Under adequate sedation, the patients underwent high speed spiral CT scanning of the thorax. Non-ionic contrast solution was injected in two patients to demonstrate the anatomical relationship between the airway and the intrathoracic large vessels. Using computer software, three-dimensional images of intrathoracic structures were then reconstructed by the radiologist. RESULTS: In all five patients the imaging results were useful in directing the physician to the correct diagnosis and appropriate management. In one patient, who had undergone repair of tetralogy of Fallot with absent pulmonary valve, the 3D-CT image showed bilateral disruptions in the integrity of the tracheobronchial tree due to compression by a dilated pulmonary artery. This patient underwent pulmonary artery aneurysmorrhaphy and required continued home mechanical ventilation via tracheostomy. In three other patients with symptoms of lower airway obstruction the 3D-CT images showed significant stenosis in segments of the tracheobronchial tree in two of them, and subsequent bronchoscopy established a diagnosis of segmental bronchomalacia. These two patients required mechanical ventilation and distending pressure to relieve their bronchospasm. In another patient who had undergone surgical repair of intrathoracic tracheal stenosis three years prior to admission the 3D-CT scan ruled out restenosis as the reason for her acute respiratory decompensation. CONCLUSIONS: 3D-CT scanning is a useful additional diagnostic tool for intrathoracic airway obstruction in paediatric patients.

Bronchial Diseases↗

PubMed1995

Mechanical ventilation with or without 7-day circuit changes. A randomized controlled trial.

OBJECTIVE: To determine whether a practice of not routinely changing ventilator circuits in patients who require prolonged mechanical ventilation is associated with an increased incidence of nosocomial pneumonia. DESIGN: Randomized controlled trial. SETTING: Intensive care units in two university-affiliated teaching hospitals. PATIENTS: 300 patients admitted to an intensive care unit who required mechanical ventilation for more than 5 days. INTERVENTION: Patients were randomly assigned to receive either no routine ventilator circuit changes or circuit changes every 7 days. MEASUREMENTS: The primary outcome measure was the incidence of ventilator-associated pneumonia. Other outcome measures included duration of mechanical ventilation, length of hospital stay, and hospital mortality. RESULTS: 147 patients were randomly assigned to receive no routine ventilator circuit changes, and 153 patients were randomly assigned to receive circuit changes every 7 days. The two groups were similar at the time of randomization with regard to demographic characteristics, intensive care unit admission diagnoses, and severity of illness. Ventilator-associated pneumonia was seen in 36 patients (24.5%) receiving no routine changes and in 44 patients (28.8%) receiving changes every 7 days (relative risk, 0.85 [95% CI, 0.55 to 1.17]). No statistically significant differences for hospital mortality, intensive care unit mortality, death during mechanical ventilation, death in patients with ventilator-associated pneumonia, or mortality directly attributed to ventilator-associated pneumonia were found between the two treatment groups (P > or = 0.11). Patients receiving changes every 7 days had 247 circuit changes costing a total of $7410; patients receiving no routine changes had a total of 11 circuit changes costing $330. CONCLUSION: The elimination of routine ventilator circuit changes can reduce medical care costs without increasing the incidence of nosocomial pneumonia in patients who require prolonged mechanical ventilation.

Adult↗

PubMed1995

Transvenous right ventricular pacing during cardiopulmonary resuscitation of pediatric patients with acute cardiomyopathy.

We describe the cardiopulmonary resuscitation efforts on five patients who presented in acute circulatory failure from myocardial dysfunction. Three patients had acute viral myocarditis, one had a carbamazepine-induced acute eosinophilic myocarditis, and one had cardiac hemosiderosis resulting in acute cardiogenic shock. All patients were continuously monitored with central venous and arterial catheters in addition to routine noninvasive monitoring. An introducer sheath, a pacemaker, and sterile pacing wires were made readily available for the patients, should the need arise to terminate resistant cardiac dysrhythmias. All patients developed cardiocirculatory arrest associated with extreme hypotension and dysrhythmias within the first 48 hours of their admission to the pediatric intensive care unit (PICU). Right ventricular pacemaker wires were inserted in all of them during cardiopulmonary resuscitation (CPR). In four patients, cardiac pacing was used, resulting in a temporary captured rhythm and restoration of their cardiac output. These patients had a second event of cardiac arrest, resulting in death, within 10 to 60 minutes. In one patient, cardiac pacing was not used, because he converted to normal sinus rhythm by electrical defibrillation within three minutes of initiating CPR. We conclude that cardiac pacing during resuscitative efforts in pediatric patients suffering from acute myocardial dysfunction may not have long-term value in and of itself; however, if temporary hemodynamic stability is achieved by this procedure, it may provide additional time needed to institute other therapeutic modalities.

Acute Disease↗

PubMed1995

The needle-wire-dilator technique for the insertion of chest tubes in pediatric patients.

We evaluated the needle-wire-dilator (NWD) technique, using commercially available sets, for insertion of chest tubes in 24 pediatric patients who were admitted to our pediatric intensive care unit (PICU). Fourteen patients had pneumothoraces, three had hemothoraces, two had pneumonia with empyema, four had pleural transudate effusions, and one had chylothorax. The ages of the patients ranged from four months to 24 years, and the sizes of the inserted chest tubes ranged from 10F to 20F. All insertions were successful, and the time from invasion of the pleural space by the needle to completion of chest tube insertion and connection to the tubing drainage system ranged from four to seven minutes. In four patients the procedure had to be performed while a significant coagulopathy existed. However, none of the 24 patients developed hemorrhagic complications. The only complication observed was a kink in the chest tube in five patients, resulting in recurrence of pneumothorax in four and pleural effusion in one. These adverse occurrences were corrected by repositioning the chest tubes in three patients, and by replacing the chest tubes with the stiffer, trochar type, chest tubes in the other two. We conclude that the NWD technique for chest tube insertion is quick, safe, and easy to perform in all pediatric age groups. The commercially available chest tubes used in our study were somewhat softer than the trochar type chest tubes available, which explains the occurrence of kinks in some of them.

Adolescent↗

PubMed1995

The effect of late-onset ventilator-associated pneumonia in determining patient mortality.

STUDY OBJECTIVE: To determine whether the development of late-onset ventilator-associated pneumonia (VAP) is associated with an increased risk of hospital mortality. DESIGN: Prospective cohort study. SETTING: ICUs of two university-affiliated teaching hospitals. PATIENTS: Three hundred fourteen patients admitted to an ICU who required mechanical ventilation for greater than 5 days. INTERVENTIONS: Prospective patient surveillance and data collection. MEASUREMENTS: The primary outcome measures were the development of late-onset VAP (ie, occurring > 96 h after intubation) and hospital mortality. RESULTS: Late-onset VAP was observed in 87 patients (27.7%). Thirty-four (39.1%) patients with late-onset VAP died during hospitalization compared with 85 patients (37.4%) without late-onset VAP (relative risk, 1.04; 95% confidence interval [CI], 0.76 to 1.43). Twenty patients (6.4%) developed late-onset VAP due to a "high-risk" pathogen (ie, Pseudomonas aeruginosa, Acinetobacter sp, Xanthomonas maltophilia) with an associated mortality rate of 65%. Stepwise logistic regression analysis identified five variables as independent risk factors for hospital mortality (p < 0.05): an organ system failure index of 3 or greater (adjusted odds ratio [AOR], 3.4; 95% CI, 2.0 to 5.8; p < 0.001), having a nonsurgical diagnosis (AOR, 2.1; 95% CI, 1.3 to 3.6; p = 0.002), a premorbid lifestyle score of 2 or greater (AOR, 1.8; 95% CI, 1.1 to 2.9; p = 0.015), acquiring late-onset VAP due to a "high-risk" pathogen (AOR, 3.4; 95% CI, 1.2 to 10.0; p = 0.025), and having received antacids or histamine type-2 receptor antagonists (AOR, 1.7; 95% CI, 1.0 to 2.9; p = 0.034). Additionally, we found the occurrence of late-onset VAP due to high-risk pathogens to be the most important predictor of hospital mortality among patients developing VAP (AOR, 5.4; 95% CI, 2.8 to 10.3; p = 0.009). CONCLUSIONS: Nosocomial pneumonia due to certain high-risk microorganisms is an independent risk factor for hospital mortality among patients requiring prolonged mechanical ventilation. We suggest that future investigations of late-onset VAP stratify patient outcomes according to the distribution of high-risk pathogens when reporting their results.

APACHE↗

PubMed1995

Ventilator-associated pneumonia: an update for clinicians.

VAP is a common problem faced by clinicians caring for critically ill patients. Use of appropriate preventive, diagnostic, and therapeutic strategies should minimize morbidity resulting from this clinical problem. Future investigations need to better define the optimum diagnostic methods and the most appropriate use of antibiotics for patients with suspected VAP. Only by developing these strategies can we hope to avoid the complications associated with spiraling empiricism. These complications include numerous outbreaks of serious antibiotic-resistant nosocomial infections due to the empiric over-administration of broad-spectrum antimicrobial agents. Advances in both the clinical and basic medical sciences are likely to help further elucidate the epidemiology and pathogenesis of VAP and, thereby, improve the opportunities for future prevention of this disorder.

Cross Infection↗

PubMed1994

Pediatric intrathoracic large airway obstruction: diagnostic and therapeutic considerations.

We describe seven patients who had intrathoracic airway obstruction resulting in severe respiratory distress. The patients were a four month old with bronchial cartilage hypoplasia presenting as congenital lobar emphysema; a one month old with segmental bronchomalacia; a one month old with tracheal bronchus; a two day old and a seven month old with aneurysmal distension of the pulmonary arteries secondary to tetralogy of Fallot, with absent pulmonary valve and atrioventricular canal with pulmonary poststenotic dilatation, respectively; a three year old with double aortic arch forming a vascular ring; and a three month old with tracheomalacia from tracheoesophageal fistula. The patients had various associated congenital defects, and all of them required one or more surgical procedures to repair the defects and relieve the airway obstruction. Five patients received endotracheal intubation with mechanical ventilation on their first admission, and three of them died postoperatively. The diagnostic workup to delineate the anatomic factors causing the obstruction, as well as to determine the therapeutic medical and surgical strategies to relieve it, are described. We conclude that the course of illness in most pediatric patients with intrathoracic airway obstruction is complex, is associated with high morbidity and mortality, and entails extensive multidisciplinary diagnostic and therapeutic efforts.

Airway Obstruction↗

PubMed1993

Overexpression of the ER-membrane protein P-450 CYP52A3 mimics sec mutant characteristics in Saccharomyces cerevisiae.

High expression of microsomal cytochrome P-450 CYP52A3 from Candida maltosa induces the formation of membrane stacks in Saccharomyces cerevisiae. Membrane proliferation is accompanied by coinduction of the ER proteins KAR2p and SEC61p and accumulation of precursor forms of proteins that have to translocate across the ER membrane (KAR2p, alpha factor). Cytosolic proteins (SSA1p and 2p) and mitochondrial proteins (CYT c1p and F1 beta p) are not affected. N-terminal truncated P-450 proteins remain in the cytoplasm and fail to induce membrane proliferation, KAR2p/SEC61p expression, and precursor accumulation. Membrane and precursor protein accumulation are typical features of sec mutants. We assume that the high amounts of P-450p block one or more factor(s) of the transport machinery and thereby cause the observed phenomena.

Amino Acid Sequence↗