Biomedical subjects

J C Post

Publications and source records attributed to J C Post.

At least 19 recordsLinked to original sources

PubMed1998

Evidence of bacterial metabolic activity in culture-negative otitis media with effusion.

CONTEXT: Otitis media with effusion (OME) can lead to significant hearing loss in children. Although previous studies have shown that bacterial DNA is present in a significant percentage of effusions sterile by culture, whether the DNA represents viable organisms or "fossilized remains" is unknown. OBJECTIVE: To determine if bacterial messenger RNA (mRNA), as detected by a reverse transcriptase-polymerase chain reaction (RT-PCR)-based assay, is present in chronic pediatric middle ear effusions that contain bacterial DNA but are sterile by standard cultural methods. Bacterial mRNAs have a half-life measured in seconds to minutes; therefore, detection of bacteria-specific mRNAs would be evidence that metabolically active organisms are present. DESIGN: Blinded comparative study. PATIENTS: A total of 93 effusions from pediatric outpatients seen for myringotomy and tube placement for chronic (>3 months) OME (median age of children, 17 months). SETTING: Tertiary care pediatric hospital. MAIN OUTCOME MEASURES: Percentage of positive test results for RT-PCR-based assays compared with culture for Haemophilus influenzae and concordance between RT-PCR and PCR-based findings for bacterial nucleic acids. RESULTS: Eleven (11.8%) of the 93 specimens tested positive by culture, PCR, and RT-PCR for H influenzae. A total of 29 specimens (31.2%) were positive by PCR but negative by culture for H influenzae. All 29 specimens were positive by RT-PCR for H influenzae-specific mRNA. CONCLUSIONS: The RT-PCR-based assay system can detect the presence of bacterial mRNA in a significant percentage of culturally sterile middle ear effusions, establishing the presence of viable, metabolically active, intact organisms in some culture-negative OME.

Biofilms↗

PubMed1998

Postoperative complications after tonsillectomy and adenoidectomy in children with Down syndrome.

OBJECTIVE: To compare the postoperative course and complications after tonsillectomy or tonsillectomy and adenoidectomy in children with Down syndrome (group 1) with the postoperative course and complications in children in a control group (group 2). DESIGN: Retrospective review of medical records for the period January 1, 1986, through March 30, 1996. SETTING: Tertiary care children's hospital. PATIENTS: The study included 87 children in group 1 and 64 children in group 2 matched for age, sex, and year of surgery. INTERVENTION: Tonsillectomy and adenoidectomy (group 1, 79 children; group 2, 57 children) and tonsillectomy (group 1, 8 children; group 2, 7 children). MAIN OUTCOME MEASURES: Length of hospitalization and postoperative complications. RESULTS: The length of hospitalization was significantly increased for the children in group 1 compared with that of children in group 2 (1.6 vs 0.80 days; P=.001, Mann-Whitney U test). Twenty-two children (25%) in group 1 required airway management or observation in the pediatric intensive care unit compared with no children in group 2 who required such care (P<.001, Fisher exact test). None of the children in either group required reintubation, continuous positive airway pressure, or tracheotomy. Respiratory complications requiring intervention were 5 times more likely in group 1 (22 [25%] vs 3 [5%]; P<.001, Fisher exact test). The median time until intake of clear liquids and duration of intravenous therapy were significantly increased in group 1 compared with group 2 (5.0 vs 4.0 hours, P=.03; 23.5 vs 16.0 hours, P=.001, respectively; Mann-Whitney U test). CONCLUSIONS: Although tonsillectomy and adenoidectomy can be performed safely in children with Down syndrome, the rate of postoperative respiratory complications is higher and the duration until adequate oral intake is resumed is longer. We therefore recommend that children with Down syndrome be admitted to the hospital overnight after undergoing tonsillectomy and adenoidectomy.

Adenoidectomy↗

PubMed1998

Blinded multiplex PCR analyses of middle ear and nasopharyngeal fluids from chinchilla models of single- and mixed-pathogen-induced otitis media.

Multiplex PCR analyses for both bacterial and viral pathogens were conducted in a blinded manner on 33 archival specimens, of known culture status, procured from chinchilla models of both single- and mixed-pathogen-induced otitis media and from a pediatric patient. These specimens had been maintained at -70 degrees C for up to 6 years. Experimental specimens evaluated included middle-ear effusions, nasopharyngeal lavage fluids and middle-ear lavage fluids from animals which were immunologically naive, sham-immunized or actively immunized with nontypeable Haemophilus influenzae antigens. Sampling times used ranged from the day of bacterial or viral challenge to 42 days after challenge. Initial PCR analyses of the 33 specimens matched the traditional culture data in 24 instances (73%), correctly identifying nontypeable H. influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, or adenovirus as the causative agent. A PCR-positive signal for the microbe(s) inoculated was also obtained in four animal model specimens (12%) which were culture negative. One of two culture-negative human effusions was also PCR positive. Thus, overall, results obtained by blinded PCR were 85% concordant with traditional culture methods or correctly indicated the specific pathogen introduced in four specimens that were sterile. In no instance was a false-positive signal obtained for any of the five etiologic agents being evaluated. We conclude that the multiplex PCR analyses are rapid and accurate methodologies when they are used to retrospectively evaluate diverse archival specimens of limited volume from experimental models of otitis media.

Adenoviridae↗

PubMed1998

Correlation between presence of viable bacteria and presence of endotoxin in middle-ear effusions.

The presence of endotoxin (detected by the Limulus amebocyte lysate assay) was compared to the presence of viable Haemophilus influenzae and Moraxella catarrhalis (detected by PCR) in 106 middle-ear effusions from pediatric patients with chronic otitis media. Endotoxin was found in 81 of the 106 specimens. Of these 81 specimens, 66 (81.5%) also tested positive for one or both of the gram-negative bacteria H. influenzae and M. catarrhalis. The data suggest that viable gram-negative bacteria, detectable by PCR but often undetectable by culture, may be the source of endotoxin in middle-ear effusions.

Adolescent↗

PubMed1998

Genetic diversity among strains of Moraxella catarrhalis: analysis using multiple DNA probes and a single-locus PCR-restriction fragment length polymorphism method.

Moraxella (Branhamella) catarrhalis, a causative agent of otitis media, sinusitis, and exacerbation of bronchitis, has acquired widespread ability to produce beta-lactamase and can be nosocomially transmitted. The typing methods used in epidemiological analyses of M. catarrhalis are not optimal for genetic analyses. Two methods, a multiple-locus Southern blot (SB) method and a single-locus PCR-restriction fragment length polymorphism (RFLP) method, were developed and used to assess genetic diversity and potential clinical and geographic relationships in M. catarrhalis. Nine randomly cloned M. catarrhalis DNA fragments were used as probes of SBs containing DNA from 54 geographically and clinically diverse strains. For comparison, a PCR-RFLP method was developed as a quick, inexpensive, and discriminating alternative. A highly variable 3.7-kb genomic region (M46) was cloned and sequenced, and 3.5 kb of the cloned DNA was targeted for PCR amplification. DNAs from the 54 strains were subjected to PCR-RFLP. SB analysis distinguished all strains that had no apparent epidemiological linkage (40 of 54), and PCR-RFLP distinguished fewer strains (21 of 54). Epidemiologically linked strains appeared genetically identical by both methods. PCR-RFLP was compared to pulsed-field gel electrophoresis (PFGE) for 8 of the 54 strains and 23 additional strains. PCR-RFLP distinguished fewer strains than PFGE typing (16 of 31 versus 20 of 31 strains), but PCR-RFLP was more useful for inferring interstrain relatedness. Separate cluster analyses of multilocus SB and single locus PCR-RFLP data showed high genetic diversity within and across geographic locations and clinical presentations. The resultant dendrograms were not entirely concordant, but both methods often gave similar strain clusters at the terminal branches. High genetic diversity, nonconcordance of cluster analyses from different genetic loci, and shared genotypes among epidemiologically linked strains support a hypothesis of high recombination relative to spread of clones. Single-locus PCR-RFLP may be suitable for short-term epidemiological studies, but the SB data demonstrate that greater strain discrimination may be obtained by sampling variation at multiple genomic sites.

Adult↗

PubMed1998

Analysis of adult otitis media: polymerase chain reaction versus culture for bacteria and viruses.

Recent studies using the polymerase chain reaction (PCR) have identified bacterial and viral genomic sequences in culture-negative pediatric middle ear effusions. To evaluate this technique in adults, 19 effusions were analyzed to compare bacterial and viral culture and PCR detection of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and adenovirus. Effusions from 4 subjects positive for human immunodeficiency virus (HIV) were analyzed by PCR for HIV virus. Three of 19 effusions were culture-positive for bacteria, and 0 of 19 for viruses. Fifteen of 19 effusions were PCR-positive for bacterial genomic sequences, and 0 of 19 for adenovirus. Thirteen of 15 PCR-positive specimens demonstrated S pneumoniae, 5 of 15 H influenzae, and 0 of 13 M catarrhalis. All 4 effusions from HIV-positive subjects were PCR-positive for HIV. No effusion was culture-positive and PCR-negative. These results confirm that culture-negative middle ear effusions contain genomic sequences from bacterial pathogens. Finding of HIV RNA and DNA in effusion from HIV-positives suggests replicating virus in this fluid.

Adenoviridae↗

PubMed1998

Comparative evaluation of culture and PCR for the detection and determination of persistence of bacterial strains and DNAs in the Chinchilla laniger model of otitis media.

This study was designed to determine the persistence of culturable bacteria versus DNA in the presence of a middle ear effusion in a chinchilla model of otitis media. Cohorts of animals were either infected with an ampicillin-resistant Haemophilus influenzae strain or injected with a tripartite inoculum consisting of freeze-thawed Streptococcus pneumoniae; pasteurized Moraxella catarrhalis; and DNA from H influenzae. The H influenzae-infected animals displayed culture positivity and polymerase chain reaction positivity through day 35. In the chinchillas infected with the low-copy number inocula of S pneumoniae, DNA was not detectable after day 1 from the co-inoculated pasteurized M catarrhalis bacteria or the purified H influenzae DNA; however, amplifiable DNA from the live low-copy number bacteria persisted through day 21 even though they were not culture-positive past day 3. These results demonstrate that DNA, and DNA from intact but nonviable bacteria, does not persist in an amplifiable form for more than a day in the presence of an effusion; however, live bacteria, while not culturable, persist in a viable state for weeks.

Ampicillin Resistance↗

PubMed1997

A practical approach to MRI of coronary artery bypass graft patency and flow.

Direct visualization of coronary artery bypass grafts can be obtained non-invasively by magnetic resonance imaging. Several studies demonstrated a high sensitivity and somewhat lower specificity for detection of vein-graft patency, using the conventional spin-echo and gradient-echo techniques. In addition, the true functional status can be assessed by determining the flowrate within the graft using phase velocity mapping. Important limitations of the previously applied techniques include the inability to accurately evaluate the different segments of jump grafts and the presence of graft stenoses. Further improvement is to be expected from the recent introduction of breath-hold imaging sequences and the forthcoming introduction of bloodpool-avid contrast agents.

Coronary Artery Bypass↗

PubMed1997

Clinical utility of two-dimensional magnetic resonance angiography in detecting coronary artery disease.

AIMS: The accuracy of magnetic resonance angiography in detecting proximal coronary artery stenoses is unclear. We postulated that fast magnetic resonance angiography is capable of (1) imaging proximal coronary arteries, and (2) detecting stenoses of > or = 50% of their luminal diameter. METHODS AND RESULTS: Thirty-five patients, referred for analysis of angina pectoris, underwent both conventional angiography and magnetic resonance angiography of coronary arteries. A fast k-space segmented gradient-echo technique was used during breath-holds. Two observers, blinded to the results of conventional angiography, independently analysed the magnetic resonance studies for (1) length of visualized segments, and (2) presence of signal voids indicative of stenoses. From 140 proximal arteries, 15 (11%) were excluded because of incomplete imaging or degraded image quality. Mean length of the visualized segments was 9 +/- 4 mm for the left main, 62 +/- 16 mm for the left anterior descending, 21 +/- 9 mm for the left circumflex and 89 +/- 32 mm for the right coronary artery. Sensitivity for detecting > or = 50% luminal diameter stenoses was 0.00 for the left circumflex, 0.53 for the left anterior descending coronary artery, 0.71 for the RCA and 1.00 for the left main artery. Specificity varied from 0.73 for the left anterior descending coronary artery to 0.96 for the left circumflex. Inter-observer agreement was 0.90. CONCLUSION: Thus, segmented magnetic resonance angiography is capable of non-invasive imaging of proximal coronary anatomy. Its good accuracy in detecting left main coronary artery disease, intermediate accuracy in detecting right coronary artery and left anterior descending coronary artery stenoses, and low accuracy in detecting left circumflex lesions fit within a range of sensitivities and specificities found by others. Further technical advances are necessary to make the technique clinically robust.

Coronary Angiography↗

PubMed1997

Pediatric respiratory papillomatosis: prognostic role of viral typing and cofactors.

Children with recurrent respiratory papillomatosis vary greatly in their clinical disease course. Many have mild disease with eventual remission while others present with an early aggressive airway obstructive course. This study consisted of 24 pediatric patients whose specimens underwent polymerase chain reaction analysis for cytomegalovirus (CMV), herpes simplex virus (HSV), and human papillomavirus (HPV) type. Nineteen of 24 specimens contained enough DNA for this study. None of the specimens were found to contain DNA from HPV-16, -18, -31, -33; CMV; or HSV, which contrasts with our previous findings in adults. Ten patients were infected by HPV-11 and seven of these underwent tracheotomy because of an aggressive tumorigenic clinical course. Nine patients were infected by HPV-6 alone of whom only two required a tracheotomy (P = 0.05, Fisher's Exact Test). The early airway obstructive course associated with HPV-11, however, had no bearing on achieving eventual disease remission, with decannulation achieved in eight of nine children.

Adult↗

PubMed1996

Munchausen syndrome by proxy complicating ear surgery.

Munchausen syndrome by proxy (MSBP) is a form of child abuse in which a parent or caretaker produces or simulates illness in a child. Often great lengths are undertaken to diagnose and treat the myriad of symptoms and problems in these children. Unnecessary examinations, treatments, and hospitalizations ensure. Unfortunately, some victims of this syndrome die. Munchausen syndrome by proxy is a form of child abuse and should be reported appropriately. The diagnosis of MSBP is difficult to make and must be done with caution as the implications for those involved are serious. Therefore, care must be taken in properly identifying cases. We present a case of MSBP complicating the postoperative course of a boy after undergoing ear surgery for cholesteatoma. Characteristics and potential clues to the diagnosis of MSBP are discussed. The goal of our article is to inform otolaryngologists of this syndrome so they may develop a high index of suspicion to better detect its occurrence.

Child, Preschool↗

PubMed1996

Pediatric fiberoptic laser rigid bronchoscopy.

Use of the fiberoptic laser for treatment of tracheobronchial lesions in the adult is well established. However, there is a paucity of experience with the fiberoptic laser in the pediatric airway. Tracheal obstruction caused by granulation tissue or stenosis, as is often seen in children, may be effectively treated with this approach. This article documents the successful use as well as the technologic advantage of the flexible fiberoptic laser systems, primarily the potassium titanyl phosphate (KTP) laser, combined with standard pediatric rigid bronchoscopic equipment in 73 procedures involving 52 children (43 children younger than five years. with an average age of 21 months). Visualization was excellent, assisted or spontaneous ventilation was well maintained, and complications were few.

Adolescent↗

PubMed1996

Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene.

Hereditary pancreatitis (HP) is a rare, early-onset genetic disorder characterized by epigastric pain and often more serious complications. We now report that an Arg-His substitution at residue 117 of the cationic trypsinogen gene is associated with the HP phenotype. This mutation was observed in all HP affected individuals and obligate carriers from five kindreds, but not in individuals who married into the families nor in 140 unrelated individuals. X-ray crystal structure analysis, molecular modelling, and protein digest data indicate that the Arg 117 residue is a trypsin-sensitive site. Cleavage at this site is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis.

Arginine↗

PubMed1996

A gene for hereditary pancreatitis maps to chromosome 7q35.

BACKGROUND & AIMS: Hereditary pancreatitis (HP) is an autosomal-dominant disorder with incomplete penetrance characterized by recurrent bouts of severe epigastric pain with onset usually at 5-10 years of age. A genetic linkage study was designed to identify the HP gene. METHODS: A 500-member pedigree was constructed from a U.S. kindred centered in eastern Kentucky and western Virginia. A genome-wide search strategy was employed using a 36-member subset of this family to determine the genetic locus for HP. Testing for linkage to microsatellite loci was performed at 20-cM intervals. RESULTS: Linkage was established between the HP phenotype and chromosome 7q in this subset of the family. Modeled as an autosomal dominant disorder with 80% penetrance, a maximal multipoint logarithm of the odds score of 4.3 was obtained using a four-point analysis consisting of markers D7S684, D7S661, D7S505, and the HP locus. Two microsatellite markers, D7S661 and D7S505, that correspond to the 7q35 region of chromosome 7 spanning a 6-cM region did not evidence obligate recombinations with HP. The centromeric and telomeric limits are defined by recombinations at D7S684 and D7S483, respectively, which generates a 19-cM locus for HP. Utilizing family members from the extended pedigree, a break in the high-risk haplotype between D7S684 and D7S661 was observed, which suggests it may be possible to exclude an additional 8 cM from the HP locus. A maximal pairwise logarithm of the odds score of 4.73 at a recombination fraction of theta at D7S684 was obtained with the addition of these extended family members. CONCLUSIONS: Linkage of HP to 7q35 represents a major advancement in our understanding of the genetic basis of this disorder.

Chromosome Mapping↗

PubMed1996

Laryngotracheal reconstruction using microplates in a porcine model with subglottic stenosis.

Current techniques of laryngotracheal reconstruction require a choice between prolonged stenting (conventional technique) or short-term stenting with maintenance of sedation and paralysis until the airway has stabilized (single-stage laryngotracheal reconstruction). An alternative method is proposed using microplates to provide immediate airway stabilization without stenting. This study was designed to evaluate the long-term effects of microplate repair of stenosis of the subglottis and trachea on the growing larynx. Subglottic stenosis was produced in piglets using a transoral endoscopic technique. Eight animals underwent repair of the stenosis using an anterior cricoid split with microplate distraction and stabilization of the cricoid cartilage and first tracheal ring. The distraction was maintained and airway growth continued for the duration of this study. However, with growth of the larynx the plates migrated away from their original position. In 50% of the animals followed up for 90 days the plates migrated into the airway lumen. This study suggests that rigid distraction of the stenotic airway with microplates is a viable alternative to more traditional methods of repair. However, plate removal at some interval after surgery is required in the growing larynx in order to prevent migration of the plate into the airway.

Animals↗

PubMed1996

Three-dimensional respiratory-gated MR angiography of coronary arteries: comparison with conventional coronary angiography.

OBJECTIVE: MR coronary angiography is most often performed using two-dimensional techniques. Although three-dimensional (3D) acquisitions do have important advantages, they take too long for a single breath-hold and are thus susceptible to respiratory motion artifacts. The purpose of this study was to investigate the accuracy of a unique respiratory-gated 3D MR angiographic technique in identifying the proximal coronary arteries in patients suspected of having coronary artery disease. In addition, we investigated the capability of this technique to detect proximal stenoses. SUBJECTS AND METHODS: We performed a prospective blinded study in 20 patients who were referred for conventional coronary angiography. A cardiac-gated 3D gradient-echo sequence with fat suppression was used. Retrospective respiratory gating was performed using navigator echoes of the diaphragm position. Using multiplanar reformatting, two independent readers blindly analyzed the data sets for visualization of major coronary arteries, lengths of imaged segments, and detection of significant stenoses (> 50% occlusion of the luminal diameter by conventional angiography). RESULTS: Seventy-seven of 80 (96%) coronary arteries were positively identified. In one patient, an anomalous coronary anatomy was readily identified and confirmed by conventional angiography. The average lengths of the imaged segments of the right, left main, left anterior descending, and left circumflex coronary arteries were 58 +/- 13 mm, 9 +/- 5 mm, 59 +/- 16 mm, and 24 +/- 10 mm, respectively. Overall sensitivity for the detection of stenoses was low (38%), with a specificity of 95%. Interobserver agreement was 0.92, with a kappa value of 0.65. CONCLUSION: Respiratory-gated 3D MR angiography allows accurate identification of proximal coronary arteries and may be valuable for 3D imaging of coronary anomalies. Further technical improvements are required to enhance the value of the technique in detecting stenoses.

Adult↗

PubMed1996

Coronary imaging using MRI.

Without use of ionizing radiation and injection of contrast material magnetic resonance imaging (MRI) can be applied to generate signal from flowing blood and create tomographic images of the bloodstream in coronary arteries, which resemble conventional contrast enhanced X-ray angiograms. The tortuosity, small diameter and motion of the coronary arteries provided technically demanding problems, which had to be solved before MR coronary angiography became realistic. Faster pulse sequences, dedicated radiofrequency receiver coils, cardiac and respiratory gating techniques were introduced and are still in the process of constant development to improve the quality of the images. To date, most clinical experience has been obtained using 2D approaches necessitating repetitive breath-holds to encompass the coronary artery tree. A substantial part of the proximal and middle parts of the coronary arteries can be visualized, which has proven to be accurate in identifying anomalous coronary anatomy and patency of proximal coronary artery bypass grafts. However, the technique is currently not sensitive enough to reliably detect coronary artery stenoses. Another approach is a single acquisition respiratory gated 3D technique which is less operator and patient dependent, requires less imaging time for an entire coronary protocol and is more comfortable for the patient than the 2D breath-hold approach. Initial experience demonstrates the capability to identify the major epicardial coronary vessels. But here too, further development is required to demonstrate coronary stenoses. A unique feature of MR imaging is the feasibility to non-invasively quantitate flow in the coronary arteries. This offers the potential to selectively determine the flow reserve of coronary arteries and to assess the functional and physiological implications of moderately severe stenoses. It can be envisaged that, although currently not apt to replace conventional coronary angiography, MR coronary angiography and flow measurement will become of use in the evaluation of specific, well defined clinical issues in coronary artery disease.

Artifacts↗

PubMed1995

Magnetic resonance angiography of anomalous coronary arteries. A new gold standard for delineating the proximal course?

BACKGROUND: The clinical significance of anomalously originating coronary arteries depends on their proximal course. Diagnosis of this course by conventional x-ray coronary angiography alone may be equivocal. We postulated that with fast magnetic resonance (MR) angiography, accurate detection of anomalous coronary arteries and unambiguous delineation of their proximal course is feasible. METHODS AND RESULTS: In a selected group of 38 patients, 19 of them having an anomalously originating coronary artery, a fast MR angiographic technique was used to study the proximal coronary anatomy. Blinded analysis of randomly ordered MR studies was performed independently by two observers. Both origin and proximal course of the coronary arteries were defined. Two cardiologists reviewed all x-ray coronary angiograms. After the separate analyses, a final consensus result was defined for each patient. In 37 patients, successful MR coronary angiography could be performed. Interobserver agreement for determining both origin and proximal course was 100%. An x-ray coronary angiogram was available in 36 patients. In 3 patients (all with an anomalous left main coronary artery originating from the right aortic sinus), there was disagreement about the proximal course between the results of MR and x-ray coronary angiography. Review of these cases demonstrated that MR angiography had unambiguously visualized the proximal coronary artery course, whereas the results of x-ray angiography had been equivocal. Thus, sensitivity and specificity for detecting anomalous coronary arteries and delineating their proximal course were 100%. CONCLUSIONS: These data suggest that fast MR angiography is highly accurate in determining the origin and delineating the proximal course of anomalous coronary arteries, even in those cases in which x-ray coronary angiographic diagnosis is difficult or even erroneous.

Coronary Angiography↗