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Biomedical subjects

D M Musher

Publications and source records attributed to D M Musher.

At least 19 recordsLinked to original sources
PubMed1992

Response of latent syphilis or neurosyphilis to ceftriaxone therapy in persons infected with human immunodeficiency virus.

OBJECTIVE: To evaluate the effect of ceftriaxone in treating latent syphilis or asymptomatic neurosyphilis in patients infected with the human immunodeficiency virus (HIV). DESIGN: Follow-up study of patients treated at two HIV-based clinics during 16 months from 1989 to 1991. PATIENTS: Patients were those in whom a clinical diagnosis of latent syphilis or asymptomatic neurosyphilis was made, who received all recommended doses of antimicrobial therapy, and who returned for follow-up visits for 6 or more months. RESULTS: Forty-three patients were treated with ceftriaxone, 1 to 2 g daily for 10 to 14 days. Thirteen underwent lumbar puncture before treatment; 7 (58%) had documented neurosyphilis (pleocytosis in 5, elevated protein levels in 6, VDRL reactive in cerebrospinal fluid [CSF] in 7), and 6 had documented latent syphilis (entirely normal CSF). The remaining 30 were said to have presumed latent syphilis. There was no relation between the diagnosis and the selected dosage of ceftriaxone. Response rates were similar in those who had documented neurosyphilis and documented or presumed latent syphilis. Overall, 28 patients (65%) responded to therapy, 5 (12%) were serofast, 9 (21%) had a serologic relapse, and 1 (2%) who experienced progression to symptomatic neurosyphilis was a therapeutic failure. Thirteen patients received benzathine penicillin for presumed latent syphilis; results were similar to those observed after ceftriaxone therapy, with 8 (62%) responders, 1 (8%) serofast, 2 (15%) relapses, and 2 (15%) failures. CD4 cell counts in responders were not different from those who failed to respond. CONCLUSIONS: Even in the absence of neurologic symptoms, half of the HIV-infected persons who have serologic evidence of syphilis may have neurosyphilis. Although ceftriaxone achieves high serum and CSF levels, 10 to 14 days of treatment with this drug were associated with a 23% failure rate in HIV-infected patients who had latent syphilis or asymptomatic neurosyphilis. Three doses of benzathine penicillin did not have a significantly higher relapse rate and may provide appropriate therapy, at least for documented latent syphilis in persons co-infected with HIV. Studies comparing ceftriaxone with 10 to 14 doses of procaine penicillin are needed to determine the most cost-effective treatment for asymptomatic neurosyphilis or presumed latent syphilis in this group of patients.

Adult↗
PubMed1992

Unusual manifestations of pneumococcal infection in human immunodeficiency virus-infected individuals: the past revisited.

Although AIDS was largely recognized and defined because of the increased presence of diseases that reflect deficiencies in cell-mediated immunity, susceptibility to common extracellular bacterial pathogens has also been shown to be increased. To our knowledge, adults with concurrent infection due to human immunodeficiency virus (HIV) and Streptococcus pneumoniae whose cases have been described to date have all had pneumococcal pneumonia and/or bacteremia. We describe five cases of HIV-infected patients who had unusual manifestations of pneumococcal infection, which include recurrent exudative pleural effusion, pyopneumothorax, purpura fulminans, mediastinitis with chest wall abscess, and multiple brain abscesses. Such complications of pneumococcal infection occurred more or less commonly in the preantibiotic era, but on the basis of our experience and an exhaustive literature search, these complications have been exceedingly rare in the past few decades. In four of our five patients, the unusual, complicated pneumococcal disease preceded and prompted a search for HIV infection. Because concurrent HIV infection increases the susceptibility to pneumococcal disease, other such cases are likely to be seen.

Adult↗
PubMed1992

Life-threatening Pseudomonas aeruginosa infections in patients with human immunodeficiency virus infection.

Bacterial infections are a well-described complication of AIDS. However, relatively few reports have described infections due to Pseudomonas aeruginosa in adults who are infected with the human immunodeficiency virus (HIV). Seven cases of serious P. aeruginosa infection in HIV-infected patients occurred during 12 months in two hospitals in Houston, often in the absence of other host factors that are generally thought to predispose to this condition. One patient had no prior illness or antibody test results that were suggestive of HIV infection; for two other patients who were known to have antibody to HIV, an AIDS-defining diagnosis had never been made. Three patients had pneumonia (two with bacteremia and one with empyema), one had malignant otitis externa, and three had bacteremia that either resulted from or caused secondarily a soft-tissue focus of infection. Two patients died, and two others experienced one or more relapses after an initial course of treatment. Compromised host defense mechanisms, including loss of mucosal integrity, defects in humoral and cellular immunities, and qualitative or quantitative leukocyte abnormalities, may predispose HIV-infected patients to P. aeruginosa infections.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Antibody to capsular polysaccharides of Streptococcus pneumoniae after vaccination of human immunodeficiency virus-infected subjects with 23-valent pneumococcal vaccine.

The Centers for Disease Control recommends that, because of a greatly increased susceptibility to pneumococcal infection, all persons infected with human immunodeficiency virus (HIV) receive pneumococcal vaccine. Using an ELISA specific for antibody to capsular polysaccharide, a postvaccination antibody was evaluated to five commonly infecting serotypes of Streptococcus pneumoniae. Thirty-nine HIV-infected persons with less than or equal to 500 CD4 cells exhibited significantly fewer responses than did healthy controls; overall, only 46 (24%) of 195 possible responses were positive compared with 45 (75%) of 60 in 12 HIV-infected subjects with greater than 500 CD4 cells and 92 (74%) of 125 in 25 healthy controls (P less than .001). Subjects with less than or equal to 500 CD4 cells responded to a mean of 1.1 antigens versus a mean of 3.8 and 3.7 in those with greater than 500 CD4 cells and controls, respectively (P less than .001). There were no differences between responses in those with less than 200 and those with 200-500 CD4 cells. Within groups stratified by CD4 cell counts, further stratification by clinical status did not reveal significant differences. Since asymptomatic HIV-infected persons with less than 500 CD4 cells show abnormal responses, pneumococcal vaccine should be given when HIV infection is first detected.

Adult↗
PubMed1992

IgG antibody reactive with five serotypes of Streptococcus pneumoniae in commercial intravenous immunoglobulin preparations.

Intravenous immunoglobulin replacement is recommended for immunoglobulin deficiency, but comparison of the efficacy of intravenous immunoglobulin preparations (IVIGs) has been hindered by the lack of standardized assays to measure immunoglobulin levels against important bacterial pathogens. IgG reactive with five commonly isolated serotypes of Streptococcus pneumoniae in four commercially available IVIGs was measured by ELISA. Specific antibody to capsular polysaccharide was quantitated before and after adsorption with cell wall polysaccharide (CWPS). All IVIGs contained measurable levels of antibody to the five pneumococcal serotypes, although the levels against an individual serotype varied by as much as sevenfold from one preparation to another. Each IVIG also contained substantial concentrations of IgG reactive with CWPS. The amount of each IVIG that protected mice was nearly identical after the doses were adjusted on the basis of specific IgG measured by ELISA, thereby providing proof in vivo of the validity of this in vitro assay system.

Animals↗
PubMed1992

In vitro activities of streptomycin and 11 oral antimicrobial agents against clinical isolates of Klebsiella rhinoscleromatis.

We tested in vitro the activities of streptomycin and tetracycline--antibiotics that have long been used to treat rhinoscleroma--as well as several newer oral agents by using 23 isolates of the causative organism Klebsiella rhinoscleromatis. All isolates were inhibited by clinically achievable concentrations of trimethoprim-sulfamethoxazole, amoxicillin-clavulanate, chloramphenicol, ciprofloxacin, cephalexin, cefuroxime, and cefpodoxime.

Anti-Bacterial Agents↗
PubMed1992

Evidence that autologous idiotypic regulation of anti-arginine-glycine-aspartic acid autoantibodies may influence development and progression of syphilitic lesions in infected rabbits.

The 83-kDa receptor protein of Treponema pallidum (TpN83) recognizes and binds fibronectin (Fn) at the amino acid sequence RGD site. By using experimentally infected animals, we have demonstrated that immunoglobulin G antibodies to this antigen and autoantibodies to the RGD site of Fn are putative components of immune complexes. This, and other findings, led us to initially hypothesize that anti-idiotypes (anti-Id) of an anti-TpN83 response are autoantibodies to RGD. Alternatively, we reasoned that if anti-Fn autoantibodies played a role in the pathogenesis of syphilis, then down-regulation of such a response by the Id network might directly affect progression of the disease. To test the hypothesis, rabbits were immunized with either affinity-purified TpN83 antigen or the synthetic Fn-7 peptide, KYGRGDS, and subsequently challenged with T. pallidum. Compared with results obtained with unimmunized, control rabbits, accelerated lesion development was noted in the rabbits immunized with TpN83. Pronounced, though unexpected, differences with respect to lesion development and progression were noted in the animals immunized with Fn-7 and then challenged intravenously; a minimal number of lesions appeared with a delayed onset. These lesions, like the localized chancres seen following intradermal challenge, were smaller and minimally ulcerated, and they healed rapidly. The Fn-7-immunized rabbits all differed from the controls in that anti-Id to anti-RGD F(ab')2 were demonstrable within 4 weeks following infection; decreases in anti-Fn autoantibody levels were associated with concomitant increases in anti-Id levels. Immunoglobulin Gs (anti-Id) from these animals following elution from anti-RGD F(ab')2 immunoaffinity columns also reacted with affinity-purified TpN83 antigen in immunoassays. These results suggest that down-regulation of autoreactive clones by manipulation of the idiotypic network in experimental syphilis warrants further investigation.

Amino Acid Sequence↗
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↗
PubMed1979

Do condom catheter collecting systems cause urinary tract infection?

A study was undertaken to determine whether use of a condom catheter collection system (CCCS) is associated with urinary tract infection (UTI). No UTI developed in 79 episodes of CCCS use in patients who were cooperative or because of paralysis were unable to manipulate the collecting system (mean time per patient, 21.2 days; total number of patient days, 1,677). By contrast, in 15 patients who were identified prospectively as being uncooperative and who repeatedly manipulated the CCS, UTI developed in eight (53.3%) within a mean of 9.6 days. Urethral catheterization in cooperative patients during CCCS use was followed by development of UTI. Repeated interference with the proper use of CCCS and urethral catheterization during CCCS use are associated with an increased risk of UTI.

Humans↗
PubMed1979

Fever patterns. Their lack of clinical significance.

Fever patterns were studied prospectively in 200 consecutive patients referred for infectious disease consultation and retrospectively in 204 patients with selected infectious or noninfectious diseases. Most patients had remittent or intermittent fever, which, when due to infection, usually followed diurnal variation. Hectic fever occurred less commonly but was observed in patients with all categories of infectious or noninfectious diseases. Although hectic fevers were seen more frequently in patients who had documented bacteremia, there were many nonbacteremic subjects who had this pattern and others without this pattern who had bacteremia. Sustained fever nearly always occurred in patients with Gram-negative pneumonia or CNS damage, although some patients with these diseases had other patterns as well. Our data suggest that, with the possible exception of sustained fever in Gram-negative pneumonia or CNS damage, the fever pattern is not likely to be helpful diagnostically.

Abdomen↗
PubMed1979

Anaerobic bacterial meningitis.

Anaerobic meningitis occurred in four patients in whom anaerobic bacteria had not been suspected as a possible cause. The predisposing conditions were typical of those seen in patients previously reported to have this infection and included chronic otitis media with mastoiditis, chronic sinusitis, recent craniotomy and abdominal trauma. Two of the patients had undergone immunosuppression (immunosuppressed patients); a compromised immune system may facilitate the development of anaerobic meningitis in patients with the appropritate underlying conditions. Head and neck neoplasms, head trauma, suppurative pharyngitis and laminectomy wounds are additional situations in which anaerobic meningitis occurs. Anaerobic bacterial meningitis probably occurs more often than is recognized. The cerebrospinal fluid should be transported and cultured anaerobically when meningitis develops in a patient with a predisposing condition.

Abdominal Injuries↗
PubMed1979

Selection of small-colony variants of Enterobacteriaceae by in vitro exposure to aminoglycosides: pathogenicity for experimental animals.

Small-colony variants of gram-negative genera of Enterobacteriaceae were selected by in vitro exposure to gentamicin. These variants were shown to have decreased susceptibility in vitro to aminoglycosides. They were lethal for mice following intraperitoneal injection, with the LD50 (50% lethal dose) being the same as, or slightly less than, that for the parent organism. Variants of strain no. 2401 of Proteus mirabilis caused urinary tract infection in mice after implantation into their bladders. Although the variants grew somewhat less rapidly than did parent organisms, both parent and variant colonies alkalinized urine at the same rate. Electron microscopic study showed no differences between colonies of parents and variants. These studies indicated that small-colony variants of Enterobacteriaceae are pathogenic for experimental animals. Further, they may cause disease in humans and should not necessarily be regarded as only laboratory curiosities.

Aminoglycosides↗
PubMed1979

Treatment of experimental nocardiosis in mice: comparison of amikacin and sulfonamide.

Recent in vitro susceptibility studies have shown that amikacin inhibits more than 90% of isolates of Nocardia. This study was designed to evaluate the effect of treatment with amikacin or sulfonamides on infection caused by Nocardia asteroides with the use of murine models. In an acute lethality model in which infection was induced by intraperitoneal injection, 13 (45%) of 29 mice that had been treated with amikacin survived, in comparison to zero of 39 untreated animals in the control group and one of 39 mice that had been treated with sulfadiazine (P less than 0.001 for amikacin). When infected with a strain of N. asteroides that was resistant to amikacin, all mice that were treated with amikacin and all untreated mice died. Drug therapy was also evaluated in a chronic infection model, in which abscesses were produced by an intraperitoneal injection of N. asteroides in saline. Treatment with either amikacin (P less than 0.001) or sulfonamide (P less than 0.02) for two to three weeks significantly increased the rate of resolution of these abscesses. These murine models demonstrate that amikacin has in vivo activity against Nocardia and may be potentially useful in the treatment of human disease.

Amikacin↗
PubMed1979

Torulopsis glabrata pneumonia in a malnourished woman.

A middle-aged woman developed malabsorption and severe protein-calorie malnutrition after a near-total gastrectomy for a perforated gastric ulcer. A transbronchial lung biopsy showed pulmonary infection with Torulopsis glabrata. Improvement in the patient's nutritional status was followed by clearing of the pneumonia without the need for antifungal chemotherapy.

Candida↗
PubMed1979

Clavulanic acid and penicillin treatment of Staphylococcus aureus renal infection in mice.

Clavulanic acid, an inhibitor of beta-lactamase, was used together with penicillin to treat infection caused by a penicillinase-producing Staphylococcus aureus. Clavulanic acid + penicillin administered to mice, prophylactically or in treatment of established infection, reduced morbidity, bacterial counts in the kidneys, and/or mortality; these differences were statistically significant when compared with those obtained by using penicillin or clavulanic acid alone.

Animals↗
PubMed1979

Effects of BCG infection on the susceptibility of mouse macrophages to endotoxin.

Mice infected intravenously with Mycobacterium bovis (BCG) are 100 to 1,000 times more sensitive to the lethal effects of bacterial lipopolysaccharides (LPS). Since BCG infection results in macrophage activation and LPS may cause pathophysiological effects through interaction with this cell type, it was of interest to determine whether macrophages from BCG-infected animals were more susceptible to the toxic effects of LPS in vitro. When LPS-susceptible, C57BL/6 mice were infected with BCG, a significant reduction in the 50% lethal dose of LPS was first observed after 7 days and persisted for several weeks. Macrophages from these animals had greatly increased susceptibility to LPS in vitro, which correlated with the development of acquired cellular resistance as determined by their ability to inhibit the growth of Listeria monocytogenes. In contrast, BCG infection of C3H/HeJ mice, a strain resistant to LPS, did not alter the 50% lethal dose of LPS for these animals or increase the sensitivity of their peritoneal macrophages to LPS in vitro. These results indicate that susceptibility of BCG-infected mice to the lethal effects of LPS parallels the susceptibility of their macrophages in vitro; release of vasoactive substances from LPS-susceptible activated macrophages in vivo may be, in part, responsible for lethality.

Animals↗