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Biomedical subjects

D M Musher

Publications and source records attributed to D M Musher.

At least 91 records · Page 5Linked to original sources
PubMed1992

Bacterial spinal epidural abscess. Review of 43 cases and literature survey.

We have reviewed our experience with 43 cases of bacterial spinal epidural abscess, as well as previously reported series of cases. We found a striking male predominance of the disease, accounting for 86% of cases. Most patients had some underlying conditions that predisposed to infection, a prior infection at a distant site, or an abnormality or trauma to the spine. Presenting symptoms included backache (72%), radicular pain (47%), weakness of an extremity (35%), sensory deficit (23%), bladder or bowel dysfunction (30%), and frank paralysis (21%). Patients cared for in public hospitals tended to seek medical attention in later stages of the disease than patients admitted to private hospitals. Spinal epidural abscess was the suspected diagnosis in only 40% of the cases; the remainder of the time various other infections, tumors, neurologic diseases, or degenerative conditions were considered. Patients in whom the diagnosis of spinal epidural abscess was not initially entertained on admission suffered delays in diagnosis and experienced neurologic deterioration. Staphylococcus aureus was the predominant pathogen (65%) and was associated with positive blood cultures in nearly every case; aerobic or facultative gram-negative bacilli were next most common. Coagulase-negative staphylococci caused infection only in patients who had previous spinal instrumentation. Although analysis of CSF was abnormal in the majority of cases, abnormalities were nonspecific, Gram stain was always negative and culture was rarely diagnostic. Abscesses extended over an average of 4 vertebrae, and the majority were located in the lumbar region followed by thoracic and cervical regions. Unlike previous series, we noted an equal frequency of anterior and posterior epidural abscesses; although differences were not statistically significant, posterior abscesses tended to be more extensive but less commonly associated with radiographic abnormalities of osteomyelitis. Myelography revealed an abnormality in every case in which it was done. Computerized tomographic scanning after intrathecal injection of contrast material always provided additional useful information. Even though magnetic resonance imaging was diagnostic in only 4 of 5 cases (80%) in our series, this test is noninvasive and clearly delineates the location and nature of spinal lesion. It should, therefore, probably replace myelography as an initial definitive study in patients suspected of having spinal infection. Plain roentgenograms and nuclear scans contributed little useful information that was not already available from other radiographic procedures. Surgical drainage together with antibiotics was the treatment of choice; 35 of our 43 patients underwent operative intervention. The preoperative status clearly predicted the final neurologic outcome.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Syphilis, neurosyphilis, penicillin, and AIDS.

Early neurosyphilis, characterized by meningitis, cranial nerve abnormalities, and cerebrospinal accidents, was first described in patients with syphilis who received inadequate courses of arsphenamine. Although more effective, penicillin at conventional doses does not yield treponemacidal levels in the central nervous system and probably does not eradicate the infecting organisms, suggesting that it works synergistically with the host's immune response in preventing neurosyphilis. Neurosyphilis after penicillin therapy was almost unheard of in the United States until it began to appear in human immunodeficiency virus (HIV)-infected patients. Numerous cases of syphilitic meningitis, cranial nerve abnormalities, and strokes have been reported in the past decade; about one-half of reported patients had received penicillin therapy, often within the previous 6 months. Thus, more intensive diagnostic evaluation, perhaps including routine cerebrospinal fluid analysis, more intensive therapy, for example with at least three doses of benzathine penicillin, and far more rigorous follow-up are indicated in HIV-infected subjects with syphilis. Since the efficacy of conventional therapy is now uncertain, novel approaches to treatment deserve systematic evaluation.

HIV Infections↗
PubMed1991

Elution of vancomycin, daptomycin, and amikacin from acrylic bone cement.

Increasing antibiotic resistance of bacteria that infect prosthetic joints has stimulated interest in the incorporation of more effective antimicrobial agents into polymethylmethacrylate (PMMA). Vancomycin and daptomycin are effective against nearly all staphylococci and streptococci, and amikacin has a broader spectrum against gram-negative bacilli than do other aminoglycosides such as gentamicin. These three antibiotics maintained bioactivity after incorporation into several commonly used preparations of PMMA and eluted readily into the surrounding medium. Preparing PMMA under negative atmospheric pressure, which decreases porosity, caused a 50% reduction in antibiotic release; the addition of 25% dextran, which increases porosity, greatly facilitated elution of these antibiotics. Based on their broad antibacterial effect against gram-positive and gram-negative bacteria, inclusion of vancomycin and amikacin in PMMA merits clinical study. The addition of these antibiotics to PMMA, together with dextran, may be applicable when structural integrity is unimportant but a substantial local antimicrobial effect is desired, such as in the use of antibiotic-containing beads to treat osteomyelitis.

Amikacin↗
PubMed1991

Pneumococcal pneumonia including diagnosis and therapy of infection caused by penicillin-resistant strains.

Attempts to rank causative agents of pneumonia in adults have placed Streptococcus pneumoniae at the top of the list. Until 10 years ago, virtually all pneumococci isolated in the United States were susceptible to less than or equal to 0.02 micrograms/mL penicillin; however, the incidence of disease caused by moderately penicillin-resistant strains has increased in the United States in the past decade. This article reviews the role of S. pneumoniae in causing pneumonia, the best methods to make the diagnosis, and the appropriate means of treatment.

Bacterial Vaccines↗
PubMed1990

Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment.

PURPOSE: To evaluate evidence that concurrent infection with human immunodeficiency virus (HIV) alters both the natural history of syphilis (by increasing the frequency of early neurosyphilis) and the response to penicillin. DATA IDENTIFICATION: Review of major works on syphilis in the English language and files maintained since 1971, supplemented by a systematic search using Index Medicus and MEDLARS. DATA EXTRACTION: The works mentioned above were critically reviewed for information on early neurosyphilis and, where relevant, HIV infection. RESULTS OF DATA ANALYSIS: The central nervous system is regularly involved in early syphilis. Standard recommended doses of benzathine penicillin provide cerebrospinal fluid levels that are probably at the borderline of efficacy, and cure relies on treatment and an adequate host immune response. Early neurosyphilis, appearing within 2 years of onset of infection with Treponema pallidum, was uncommon in the prepenicillin era and usually occurred after inadequate therapy. This complication was exceedingly rare in the first three decades of penicillin use. In contrast, in the past decade, 40 patients with HIV infection have been reported to have asymptomatic neurosyphilis, or syphilitic meningitis, cranial nerve abnormalities (predominantly in cranial nerves II and VIII), or cerebrovascular accidents, singly or together. In 40% of cases, HIV infection was first diagnosed when neurologic symptoms appeared. Of the 38 patients for whom information was available, 18 had the acquired immunodeficiency syndrome (AIDS), 7 had AIDS-related complex, and 13 had antibody to HIV. Sixteen had previously been treated for syphilis, of whom 5 (31%) had received benzathine penicillin within the previous 6 months. Preliminary data also suggest that skin lesions and VDRL (Venereal Disease Research Laboratory) antibody in HIV-infected patients with secondary syphilis respond more slowly to conventional penicillin therapy. CONCLUSION: Intensive therapy and follow-up observation is indicated for early syphilis in HIV-infected subjects. Novel approaches to treatment deserve systematic evaluation.

HIV Infections↗
PubMed1990

Pneumococcal polysaccharide vaccine in young adults and older bronchitics: determination of IgG responses by ELISA and the effect of adsorption of serum with non-type-specific cell wall polysaccharide.

Available pneumococcal vaccines provide only limited protection for certain at-risk populations. Fifteen healthy young adults and 11 older chronic bronchitics received 23-valent pneumococcal vaccine. ELISA showed that IgG reactive with capsular polysaccharides from Streptococcus pneumoniae serotypes 3, 4, 8, 14, and 19F increased after vaccination. Bronchitics exhibited lesser responses for four of these serotypes, although differences between the groups were significant only for serotype 3. Adsorption of postvaccination sera with pneumococcal cell wall polysaccharide significantly reduced mean antibody levels in both groups and lowered the proportion of sera that demonstrated type-specific antibody responses. Reactive IgG was largely restricted to the IgG2 subclass. Pneumococcal vaccine may provide suboptimal protection of older adults because antibody responses to some capsular polysaccharides are lower in elderly bronchitics than in healthy young adults. A substantial proportion of measured antibody reflects IgG reactive with cell wall polysaccharides rather than with type-specific, capsular constituents, suggesting that antibody responses in subjects of all ages deserve reappraisal.

Adsorption↗
PubMed1990

Does naturally acquired IgG antibody to cell wall polysaccharide protect human subjects against pneumococcal infection?

Antibody to the non-serotype-specific cell wall polysaccharide (CWPS) of Streptococcus pneumoniae has been said to confer a degree of non-serotype-specific protection against pneumococcal infection. The hypothesis underlying the present study was that if this antibody is protective, relatively higher levels are likely to be detected in patients who are colonized by pneumococci but do not have infection, those who have febrile bronchitis but do not have pneumonia, and those who have pneumococcal pneumonia but are not bacteremic. Mean IgG reactive with CWPS by ELISA in 15 healthy young adults was 43.9 micrograms/ml and in 126 randomly selected hospital patients of all ages was 41.9 micrograms/ml. In subjects with chronic bronchitis with or without known pneumococcal carriage, mean anti-CWPS IgG was 87.7 micrograms/ml. In three groups of patients (3 with acute purulent tracheobronchitis, 13 with nonbacteremic pneumococcal pneumonia, and 14 with S. pneumoniae bacteremia) at the time of admission, mean antibody levels were essentially identical, 104.9-110.1 micrograms/ml. The data suggest that naturally present anti-CWPS IgG does not protect against the evolution of acute pneumococcal infection from colonization to acute purulent bronchitis, from bronchitis to pneumonia, or from pneumonia to bacteremia.

Adsorption↗
PubMed1990

The effect of HIV infection on phagocytosis and killing of Staphylococcus aureus by human pulmonary alveolar macrophages.

Pulmonary alveolar macrophages (PAM) play a central role in host defense against pulmonary infection. The authors studied the number, viability, and ultrastructure of PAM recovered by bronchoalveolar lavage from normal and HIV-infected subjects, and their ability to phagocytose and kill Staphylococcus aureus. PAM from HIV-infected subjects who did not have pneumonia were present in greater numbers and phagocytosed significantly more opsonized Staphylococcus aureus (32.5% and 27.3% for nonsmokers and smokers, respectively) than did PAM from healthy controls (19.5% and 18.2%). In 15 patients with AIDS and pneumonia (due to Pneumocystis carinii in 13/15), viability of PAM and their phagocytic capacity were significantly reduced; in smokers with AIDS and pneumonia, the PAM yield was also dramatically decreased. Killing of S. aureus was similar by PAM from all patient groups. HIV infection was associated with the electron microscopic finding in PAM of extensively ruffled PAM cell-surfaces and ingestion of lymphocytes. Thus, HIV infection stimulates the phagocytic capacity and produces morphologic changes consistent with the possibility that PAM are activated by this retroviral infection. In patients with AIDS who develop pneumonia, especially in smokers, the number, viability and phagocytic capacity of PAM are significantly decreased; our study could not determine whether this diminished activity reflects evolution of the HIV infection or a secondary effect of the pneumonia.

Adult↗
PubMed1990

Pneumococcal vaccination: work to date and future prospects.

In our opinion, the conclusion from all these studies is that pneumococcal polysaccharides in the form in which they have been administered are relatively poor immunogens when compared, for example, to certain proteins such as tetanus toxoid. Had pneumococcal vaccination been the success that might reasonably have been predicted, there would be no argument, this many years later, over its merits. Although polysaccharide vaccines appear to have been effective in mass vaccination programs and in epidemic situations where presumably healthy adults have been involved, it has been more difficult to document their efficacy in individuals who are most in need of them, namely those with aberrant or senescent immune systems. There seems to be no disagreement that antibody at some concentration (the precise level remains to be determined) will, in general, be associated with protection, although in any one individual, for a variety of reasons, infection with a vaccine serotype might still occur. Thus, the clear direction for the future should be not to argue further the merits of currently available vaccine preparations, but rather to work rapidly and efficiently to develop and test new and more effective polysaccharide antigens. Studies in the past 10 years have shown that the polyribosyl ribitolphosphate (PRP) of Haemophilus influenzae type b is a far more effective antigen when conjugated to diphtheria toxoid. For example, in a study in our laboratory, vaccination of healthy young adults with PRP-conjugated diphtheria toxoid yielded serum antibody levels 10- to 100-fold higher than after PRP alone. Responses may be even better if other proteins are used.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial↗
PubMed1990

Immunoglobulin class and subclass restriction of autoimmune responses in secondary syphilis.

The immunoglobulin (Ig) class and IgG subclasses of autoantibodies to commercial VDRL antigen, creatine kinase (CK), and fibronectin (Fn) in the sera of patients with various stages of syphilis were quantified using solid-phase radioimmunoassays (RIA) and ELISA. Sera from patients with active secondary syphilis, initially positive for anti-Fn and anti-CK autoantibodies by RIA, were re-evaluated by ELISA using monoclonal antibodies (MoAb) for detection of human Ig class and subclass responses. Results of these assays revealed that anti-Fn and anti-CK responses were not only IgG in nature, but dramatically skewed to IgG1 and IgG3 subclasses. While the restricted, co-expression of these isotypes seemingly paralleled anti-treponemal activity, inverse relationships actually existed between the subclass responses to Fn and those to Treponema pallidum. In contrast, anti-VDRL were predominantly IgM in 17 of 22 patients. Of those sera exhibiting detectable anti-VDRL IgG activity, responses appeared to be restricted to IgG1. These results suggest that different control mechanisms may be responsible for regulation of the various autoantibody responses expressed during syphilitic infection.

Adult↗
PubMed1990

Quantitative relationship between anticapsular antibody measured by enzyme-linked immunosorbent assay or radioimmunoassay and protection of mice against challenge with Streptococcus pneumoniae serotype 4.

We have recently shown that a substantial proportion of antibody to pneumococcal polysaccharide as measured by enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay is removed by adsorption with pneumococcal cell wall polysaccharide (CWPS). The present study was undertaken to validate the hypothesis that only serotype-specific antibody that remains after adsorption with CWPS provides protection against pneumococcal infection. Serum samples were obtained from human subjects before and after they had been vaccinated with pneumococcal polysaccharide vaccine. Antibody to Streptococcus pneumoniae serotype 4 was measured by ELISA without adsorption or after adsorption of serum with CWPS. Groups of mice were injected with graded doses of serum and then challenged intraperitoneally with 10, 100, or 1,000 50% lethal doses (LD50) of S. pneumoniae serotype 4. Without adsorption, prevaccination sera from five healthy adults appeared to contain up to 33 micrograms of antibody to S. pneumoniae serotype 4 antigen per ml; adsorption with CWPS removed all detectable antibody, and pretreating mice with up to 0.1 ml of these sera (less than or equal to 3.3 micrograms of antibody) failed to protect them against challenge with 100 LD50. In contrast, postvaccination sera contained 2.9 to 30 micrograms of antibody per ml that was not removed by adsorption. Diluting sera to administer desired amounts of serotype-specific immunoglobulin G showed a significant relationship between protection and antibody remaining after adsorption (P less than 0.05 by linear regression analysis); 150 ng was uniformly protective against 1,000 LD50, and 50 ng was protective against 100 LD50. These studies have, for the first time, quantitated the amount of serotype-specific antibody that protects mice against challenge with S. pneumoniae type 4. In light of these observations, it is necessary to reassess current concepts regarding the presence of antipneumococcal antibody in the unvaccinated population, responses to pneumococcal vaccination, and protective levels of immunoglobulin G.

Adult↗
PubMed1990

Interruption of capsule production in Streptococcus pneumonia serotype 3 by insertion of transposon Tn916.

Transposon Tn916 mutagenesis was used to produce mutant strains of Streptococcus pneumoniae serotype 3 that lacked only a polysaccharide capsule. Southern blotting, DNA-DNA hybridization, and immunochemical analyses demonstrated that the presence of a single copy of Tn916 was sufficient to produce unencapsulation. The 50% lethal dose for such mutants was greater than 5 x 10(7) CFU, as opposed to a 50% lethal dose of 1 CFU for wild-type strains. These experiments outline an effective method for targeting genes in S. pneumoniae by transposon interruption and provide molecular evidence to support the longstanding hypothesis that the capsule is the principal virulence factor in this pathogen.

Animals↗
PubMed1989

Cutaneous manifestations of bacterial sepsis.

In short, bacterial sepsis is associated with a number of peripheral manifestations involving the skin and soft tissues. The pathogenesis of the lesions observed is not fully understood and is almost certainly multifactorial. In ecthyma gangrenosum, the presence of large numbers of gram-negative bacilli in the walls of small blood vessels without a substantial inflammatory response suggests that either the bacteria themselves or bacterial products are responsible for tissue damage. Endotoxin probably plays a prominent role in producing these lesions. That Pseudomonas and Aeromonas species seem to cause ecthyma out of proportion to their prevalence as a cause of bacteremia might suggest that the endotoxin of these organisms has a special predilection for skin and subcutaneous structures. More likely, it indicates that other bacterial substances, such as exotoxins or proteases, are involved. The absence of PMN leukocytes is thought to play a permissive role, allowing unopposed bacterial proliferation. Lesions of symmetric peripheral gangrene characteristically do not have bacteria present. The presence of intravascular fibrin accumulation probably resembles the generalized Shwartzman phenomenon. However, the gangrenous lesions themselves more likely result from systemic hypotension and the resulting hypoperfusion of the tissues than from vessel obstruction. In lesions associated with vigorous inflammatory response, bacterial products may damage tissue either directly or by attracting leukocytes that, in turn, release substances that cause further tissue damage. An etiologic role for endotoxin or the gram-positive bacterial cell wall is likely, since endotoxin is known to produce similar lesions in the localized Shwartzman reaction. Favoring a role for other bacterial substances is the predisposition of V. vulnificus to cause cellulitis or of C. fetus to cause inflammation of the major vessels during sepsis; the mechanisms for these reactions are entirely unknown. It is interesting that in most instances in which peripheral lesions are caused by sepsis, either a large number of bacteria or an intense inflammatory response by PMNs is present, but not both. In both kinds of lesion, the tendency to involve blood vessels by different pathogenetic mechanisms contributes to the evolution of the disease process. In intensely inflamed lesions, veins and arteries can be shown histologically to be occluded. In the absence of inflammation, bacterial invasion of vessel walls or simply the presence of bacterial products adjacent to the vessel may produce spasm. As noted, the pathogenetic significance of thrombosis observed in the lesions of DIC remains unclear.(ABSTRACT TRUNCATED AT 400 WORDS)

Ecthyma↗
PubMed1989

Chronic cavitary histoplasmosis. Failure of oral treatment with ketoconazole.

Ketoconazole appears to be a safe drug in the treatment of chronic cavitary histoplasmosis. Primary failure and relapse have been described, requiring amphotericin B, even after long therapy with ketoconazole. Four typical cases are presented. We caution about such potential failures and stress the importance of close observation of patients begun on therapy with ketoconazole for chronic cavitary histoplasmosis.

Administration, Oral↗