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Biomedical subjects

J M Bernstein

Publications and source records attributed to J M Bernstein.

At least 73 records · Page 4Linked to original sources

Choice of antibiotics, pharmacokinetics, and dose adjustments in acute and chronic renal failure.

A multitude of antimicrobial agents have become available over the past two decades. Appropriate use of these drugs demands not only an understanding of the antimicrobial spectrum of the agent but of the necessary dose adjustments because of renal or hepatic impairment. The use of computer-assisted pharmacokinetic modeling for dosing potentially toxic drugs such as aminoglycosides and vancomycin should be utilized whenever possible.

Acute Kidney Injury↗

Macrophage (monocyte)-derived mucous secretagougue (MMS) is released into the fluid of the middle ear of patients with otitis media with effusion.

Macrophage (monocyte)-derived secretagogue (MMS) is a low molecular weight peptide released by activated macrophages. This substance can enhance incorporation of carbohydrates into protein and result in the production of glycoproteins. It is believed that increased glycoproteins lead to the increased tenaciousness of mucoid effusions. Sixteen of 28 middle ear effusions demonstrated significant amounts of MMS. It is suggested that MMS is produced by activated macrophages in MEE and may lead to the development of glycoprotein by secretory epithelial cells. This substance may lead to the development of the mucoid effusion in otitis media with effusion in children.

Adolescent↗

Human adenoidal organ culture: a model to study nontypable Haemophilus influenzae (NTHI) and other bacterial interactions with nasopharyngeal mucosa--implications in otitis media.

Nontypable Haemophilus influenzae (NTHI) has become the predominant cause of both acute suppurative otitis media and chronic otitis media with effusion. It has now been well-demonstrated that both outer membrane proteins and restriction fragment analysis of the bacterial genomes of concomitant nasopharyngeal and middle ear effusion isolates of NTHI are identical. It is therefore of critical importance to understand the mechanisms whereby bacteria that are present in normal healthy children in small numbers become the predominant organism in the nasopharynx in otitis media. The studies presented here suggest that nontypable Haemophilus influenzae can effectively decrease ciliary function as measured by stroboscopic illumination of ciliary beat frequency on human adenoidal organ culture. This organism also produces significant histopathologic and ultrastructural damage to the epithelial cells and cilia of adenoid organ culture, demonstrated by both light microscopy and scanning electron microscopy. The data suggest the following hypothesis: nontypable Haemophilus influenzae can destroy mucociliary function and allow increased bacterial replication in the mucus overlying the nasopharyngeal mucosa. The mucociliary system of the eustachian tube may also be involved in a similar manner, thus allowing bacteria to enter the middle ear space via the eustachian tube.

Adenoids↗

Reducing the cost of surgical prophylaxis.

A four-part program was implemented in order to control the rising cost of prophylactic antibiotics: limiting the number of cephalosporins on formulary; prohibiting the use of third- and most second-generation cephalosporins for prophylaxis; using a special order form to designate use as empiric, therapeutic, or prophylactic; and mandatory discontinuance of prophylactic antibiotics after 24 hours. The total cost for administration of prophylactic antibiotics was reduced from an average of $37.35 per case for the six months preceding the start of these restrictive policies to an average of $21.99 per case during the next twelve months. Class I and class II wound-infection rates were 2.0 per cent and 4.9 per cent, respectively, prior to the adoption of the new antibiotic practices. Comparable infection rates were 1.8 per cent and 2.1 per cent, respectively, after this program was initiated. The rising cost of antibiotic prophylaxis can be reduced without adversely affecting wound-infection rates.

Cefazolin↗

Comparison of oral and aerosol ribavirin regimens in the high risk elderly.

A comparison of different regiments of ribavirin (R), administered either orally or by aerosol, was performed in 16 elderly subjects (13 men, 3 women, mean age 63 +/- 8 years) considered to be in the "high-risk" category for complications from influenza as defined by the Centers for Disease Control. The subjects were divided into four groups. Group O-600 received 600 mg orally R every 8 hours for 48 hours followed by 200 mg every 8 hours for 72 hours for a total dose of 5.4 g (22.1 mmol). Group O-800 received 800 mg oral R every 8 hours for 24 hours followed by 400 mg every 12 hours for 96 hours for a total dose of 4.1 g (22.9 mMoles). Group A-40 received R (40 mg/ml) aerosolized through a small particle aerosol generator for 6 hours every 12 hours for 96 hours, yielding an average delivered dose of 6.2 g (25.4 mMoles) R. Group A-60 received aerosolized R (60 mg/mL) for 2 hours every 8 hours for 96 hours, yielding an average delivered dose of 4.6 g (18.8 mMoles) R. No hematologic or other laboratory abnormalities were associated with any of the regimens. Group O-800 and O-600 reached mean peak plasma R levels of 11.8 microM and 5.3 microM, respectively, after 18 hours of therapy. Subsequent administration of 20 mg R every 8 hours was sufficient to maintain a plasma R level greater than 7 microM. Among the aerosol groups, group A-40 approached steady state plasma R levels (8-10 microM) more quickly than group A-60.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Determination of the epidemiology and transmission of nontypable Haemophilus influenzae in children with otitis media by comparison of total genomic DNA restriction fingerprints.

It is assumed that the causative bacteria in children suffering from otitis media reach the middle ear via the eustachian tube. The purpose of this investigation was to use endonuclease restriction of bacterial chromosomal DNA to compare isolates of nontypable (NT) Haemophilus influenzae obtained from the nasopharynx and from middle ear (ME) effusions of patients with otitis media. Strains of NT H. influenzae were isolated from the nasopharynx (NP) and affected ME from a group of 13 unrelated children with otitis media with effusion (OME). For 12 of these children, identical strains were isolated from the NP and ME in a first episode of OME. Each of these 12 sets differed from the other 11. Six of these children suffered from a second episode of OME with NT H. influenzae. Five of these children with recurrence again had identical NP and ME strains. These results suggest that at the time of an episode of OME, there is one predominant strain of NT H. influenzae that colonizes both the NP and ME. The strains of NT H. influenzae isolated from all six of the second episodes were different from strains from the first episode, indicating turnover of the predominant strain in the NT H. influenzae population between episodes. When we investigated three siblings with concurrent episodes of OME, we found that they shared several similar strains of NT H. influenzae, thereby demonstrating that within a family, transmission of NT H. influenzae from child to child is possible. These results from DNA fingerprinting were essentially identical when compared with results from outer membrane protein subtyping performed on the same set of strains. The analysis of endonuclease restriction patterns of total genomic DNA provides a sensitive measure of genetic dissimilarity between strains and represents an easily applicable method for epidemiological and transmission studies of bacterial infections associated with NT H. influenzae.

Bacterial Outer Membrane Proteins↗

Restriction fragment mapping of nontypable haemophilus influenzae: a new tool to study this middle ear pathogen.

Isolates of nontypable haemophilus influenzae (NTHI) recovered from paired nasopharyngeal (NP) and middle ear (ME) fluid cultures performed simultaneously on seven children with otitis media with effusion (OME) were studied by analysis of the restriction fragment patterns produced from total genomic DNA. This method provides a sensitive measure of the genetic similarities between strains. In the seven pairs examined, the NP and ME strains were indistinguishable from one another, whereas each pair was distinct from the other, except for two siblings in whom all four strains were identical. This information provides evidence that the pathogenesis of OME caused by NTHI involves spread of the bacteria from NP to the ME. Analysis of paired NP and ME isolates from three children with recurrent OME caused by NTHI indicated that the second episode was caused by the reinfection with a different strain rather than persistence and reemergence of the first strain. Finally, DNA analysis of strains from two siblings with concurrent OME suggested that person-to-person transmission of NTHI can occur among children. These findings suggest that at any one time the NTHI population in the NP is relatively homogenous, at least at the time of acute upper respiratory disease. Our observation that the strains present at the second episode of otitis media were different than the strains present in the first episode is consistent with strain replacement in the NP. Restriction fragment mapping analysis of genomic DNA of NTHI could provide a powerful tool for investigating the rate of turnover of the NTHI population in the NP.

Child, Preschool↗

Characteristics of in vitro production of mucosal antibody to respiratory syncytial virus in tonsillar tissue lymphocytes.

Tonsillar lymphocytes (TL) obtained from 39 subjects were established in culture in vitro, and analyzed for respiratory syncytial virus (RSV) specific antibody synthesis after stimulation with pokeweed mitogen and live or ultraviolet light inactivated RSV. Following stimulation with the virus, IgG1, IgA, and low levels of IgG3 but no IgG2, IgG4, or IgE anti-RSV antibody could be detected in the culture supernatants. The anti-RSV antibody production in TL did not show any correlation with the preexisting levels of anti-RSV antibody in the serum of the subjects. TL collected prior to RSV infection in the community exhibited low levels of RSV antibody synthesis. On the other hand, TL obtained during the months of natural exposure to RSV exhibited significantly higher anti-RSV antibody production. TL from atopic children demonstrated IgA anti-RSV antibody more frequently and in higher content than the TL from nonatopic children. There were no significant differences in antibody production in IgG1 and IgG3 subclasses in these subjects. These observations suggest that mucosal lymphoid tissue participates in IgG1 subclass antibody production. It is also suggested that mucosal infections correlate better with local antibody synthesis than with serum antibody activity.

Antibodies, Viral↗

Leukotriene C4 release in upper respiratory mucosa during natural exposure to ragweed in ragweed-sensitive children.

With high-pressure liquid chromatography and specific radioimmunoassay, the concentration of leukotriene C4 (LTC4) was measured in nasopharyngeal secretions (NPS) of groups of children with allergic rhinitis before, during, and after the ragweed-pollen season. Increase LTC4 concentrations in NPS were noted in all the children during the pollen season; the concentration of LTC4 increased from a preseasoned mean of 1.87 +/- 0.43 ng/ml to 5.52 +/- 0.7 ng/ml at the peak of the ragweed season (p less than 0.001). The mean LTC4 concentration 2 weeks after the end of the ragweed season declined only to about 4.45 +/- 1.04 ng/ml. The seasonal variation of LTC4 concentrations and symptom scores of the children paralleled the pattern of the ragweed-pollen count. All children studied were ragweed sensitive, and six children were additionally sensitive to Alternaria (mold). The mold-sensitive children demonstrated higher concentrations of LTC4 in their NPS before and continued to have high LTC4 levels after the peak ragweed season, coinciding with peaks of mold-spore counts. Data presented in this study suggest that mast cells and other target cells in the nasal mucosa of children with allergic rhinitis produce pharmacologically active mediators, such as LTC4, during natural exposure to ragweed or Alternaria.

Adolescent↗

Recent advances in immunologic reactivity in otitis media with effusion.

The role of IgE-mediated hypersensitivity in the development of middle ear disease has not been completely resolved. However, on the basis of our investigations and those of other laboratories, we suggest that approximately two thirds of patients with chronic recurrent otitis media do not have allergies. The other third may have allergic rhinitis, and this allergic rhinitis could play a direct role in producing eustachian tube dysfunction in recurrent otitis media. However, viral infections of the upper respiratory tract may also induce IgE-mediated release of mast cell inflammatory mediators, and could cause otitis media on the basis of viral infection alone. Subtle immunologic deficiencies involving the IgG2 subclass and other immunoglobulin subclasses may also be lower in otitis-prone children, and this may be a genetically inherited disorder. Finally, the possibility of food allergy in otitis media must be considered, particularly in the young otitis-prone child with chronic recurrent otitis media.

Antigen-Antibody Reactions↗

Rapid diagnosis of influenza A and B by 24-h fluorescent focus assays.

Murine monoclonal antibodies directed against type-specific antigens of influenza A and B viruses have been shown to be useful diagnostic reagents for the detection of influenza viruses by immunofluorescence testing of nasopharyngeal cells. We have developed fluorescent focus assays utilizing these antibodies in cell culture chamber slides and shell vials for the rapid diagnosis of influenza A and B. Chamber slide assays were compared with virus isolation in 160 specimens from 135 patients with symptoms of influenza. Virus isolation was compared with immunofluorescence testing in 38 of the 160 specimens. Compared with virus isolation, 24-h cell culture chamber slide assays had a sensitivity of 75% and a specificity of 96%. Immunofluorescence testing of nasopharyngeal cells was only 38% sensitive and 91% specific. Shell vial assays were compared with virus isolation for 89 specimens. At 16 to 18 h postinoculation, the shell vial assay was 84% sensitive and 100% specific. We conclude that both chamber slide and shell vial assays are rapid, sensitive, and specific techniques for the diagnosis of influenza.

Animals↗

The distribution of immunocompetent cells in the compartments of the palatine tonsils in bacterial and viral infections of the upper respiratory tract.

Employing a series of monoclonal antibodies directed against T cell subsets using the avidin-biotin complex method as the immunoperoxidase technique and using fluorescein-conjugated antisera directed against the major immunoglobulins, we have studied the distribution of immunocompetent cells in sections of tonsils from 21 patients with various inflammatory diseases of the tonsils, including Streptococcal tonsillitis, recurrent tonsillitis and tonsillitis associated with infectious mononucleosis. The following conclusions can be made in regard to our study. The percentage of T cells decreases in all compartments of the tonsils with increasing episodes of tonsillitis as well as with infectious mononucleosis and Streptococcal tonsillitis. Similarly, the percentage of HLA-DR positive cells decreases with increasing episodes of tonsillitis and is statistically significant in the mantle zone. The percentage of IgM B cells and IgD B cells tends to increase in the extrafollicular zone and decrease in the mantle zone with increasing episodes of tonsillitis as well as with increasing age. The percentage of IgG and IgA plasma cells is highest in children who have had 3-5 episodes of tonsillitis, but markedly decreases in the follicle and extrafollicular compartments in patients who have had more than 5 episodes of tonsillitis. FACS analysis of B cells in the tonsils and peripheral blood show a marked decrease in IgD in both the tonsil and the peripheral blood and a significant increase of IgG in the peripheral blood. These findings may suggest late clonal expansion of B cells in recurrent tonsillitis and Streptococcal tonsillitis. Finally, the distribution of immunocompetent cells in recurrent tonsillitis, Streptococcal tonsillitis and tonsillitis associated with infectious mononucleosis appears to be independent of age.

Adolescent↗

Eustachian tube function associated with histamine-induced and ragweed-induced rhinitis.

Nasal allergies may contribute to Eustachian tube dysfunction and chronic middle ear problems. In exploring this association further, Eustachian tube function was measured in ten ragweed-allergic and eight non-allergic patients undergoing repetitive nasal provocation. Anterior nasal provocation was done using paper disks impregnated with either histamine or aqueous ragweed allergen. Increasing concentrations of the provocative agent were placed on both inferior nasal turbinates until moderate symptoms of rhinitis developed. Eustachian tube function was evaluated using the 9-step inflation-deflation tympanometric test before and immediately after each nasal challenge. Eustachian obstruction developed in 4 of 38 non-allergic ears during histamine nasal provocation. With ragweed nasal challenge, 9 of 42 allergic ears developed Eustachian tube obstruction. Four allergic ears gained Eustachian tube function despite being obstructed before the challenge. The observed changes in ear function for both groups were not significant due to variability in Eustachian response. At the concentrations which initiated symptoms of rhinitis, nasal provocation with histamine or ragweed did not consistently obstruct the Eustachian tube. We conclude that mild symptoms of allergic rhinitis may not cause significant Eustachian tube obstruction.

Airway Resistance↗

Modulation of monocyte Mo2 surface antigen expression by exposure to respiratory syncytial virus.

The Mo2 antibody recognizes a monocyte-specific cell surface antigen of unknown function. Upward modulation of Mo2 surface epitope density was demonstrated in response to 72-hr culture of monocytes with respiratory syncytial virus (RSV), but this was not seen after culture with phytohemagglutinin or other respiratory viruses. Monoclonal antibody probes for RSV proteins were used to demonstrate probable replication of RSV proteins in peripheral blood monocytes and pulmonary alveolar macrophages. These data provide possible clues to the biologic role of the Mo2 antigen.

Antibodies, Monoclonal↗

Outer membrane protein and lipooligosaccharide analysis of paired nasopharyngeal and middle ear isolates in otitis media due to nontypable Haemophilus influenzae: pathogenetic and epidemiological observations.

We studied isolates of nontypable Haemophilus influenzae from cultures of nasopharynx and middle ear fluid (MEF) done simultaneously on children with otitis media. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of outer membrane protein (OMP) patterns demonstrated that in 16 of 19 pairs, the nasopharyngeal and MEF strains were identical. With four monoclonal antibodies to lipooligosaccharide (LOS) determinants, 17 of the 19 pairs were identical. Thus the pathogenesis of otitis media due to nontypable H. influenzae appears to involve spread of the bacteria from the nasopharynx to the middle ear. Analysis of middle ear isolates from four children with recurrent otitis media caused by nontypable H. influenzae indicated that the recurrent episodes were caused by reinfection with different strains rather than by persistence of the same strain. OMP and LOS analysis of strains from two sisters with concurrent otitis media suggested that person-to-person transmission of nontypable H. influenzae can occur among children.

Antibodies, Monoclonal↗

Oral ribavirin treatment of influenza A and B.

A loading dose and short-term administration of oral ribavirin significantly improved symptoms and signs of influenza type A or B infection in 25 patients. The antiviral effect was not significant. No adverse clinical effects or significant laboratory values were observed. Oral treatment of patients with influenza A or B infection might be possible with ribavirin.

Administration, Oral↗