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Biomedical subjects

D M Musher

Publications and source records attributed to D M Musher.

At least 163 records · Page 9Linked to original sources
PubMed1983

The effect of staphylococcal peptidoglycan on polymorphonuclear leukocytes in vitro and in vivo.

The ability of Staphylococcus aureus to resist phagocytosis by polymorphonuclear leukocytes (PMN) is thought to be an important virulence factor for this microorganism. We have studied the effect of peptidoglycan (PG) on PMN function in vitro, and on the induction of leukopenia in vivo. Phagocytosis and chemotaxis by human PMN were both inhibited in vitro by prior incubation with as little as 2.5 micrograms PG/ml. Control PMN phagocytized 85% of added bacteria, while PMN treated with PG for 30 minutes phagocytized only 45% of the bacteria. Also, PG-treated PMN did not migrate towards an attractant. Suppression of PMN function by PG could be abolished when PG was incubated with antiserum raised in rabbits against PG. PMN incubated with PG generated a burst in oxygen metabolism as measured by the emission of chemiluminescence. When PG (500 micrograms) was given to rats or guinea pigs, the animal developed an early leukopenia which paralleled a drop in blood pressure and in thrombocyte levels, and in the concentration of hemolytic complement. Leukopenia was less in animals treated with cobravenom; an agent known to deplete complement. Antihistaminics had no effect on the induction of leukopenia by PG. We conclude that PG may be at least partly responsible for leukopenia sometimes observed in patients with life-threatening staphylococcal infections, and this leukopenia might be due to a direct or indirect toxic effect of PG on the PMN.

Adult↗
PubMed1982

Fever of unknown origin: diagnostic principles.

Almost by definition, diagnostic evaluation of a patient with fever of unknown origin remains a challenging problem. Before turning to lengthy checklists and a battery of sophisticated invasive procedures, the physician should pursue all possibilities suggested by the patient's clinical and epidemiologic history. Four illustrative cases are presented to exemplify this logical approach.

Accidents↗
PubMed1982

Reappraisal of lymphocyte responsiveness to concanavalin A during experimental syphilis: evidence that glycosaminoglycans in the sera and tissues interfere ith active binding sites on the lectin and not with the lymphocytes.

No significant differences were noted between the responses of lymphocytes from normal and Treponema pallidum-infected rabbits to concanavalin A. When added to cultures of normal peripheral blood lymphocytes, however, sera and tissue supernatant fluids from infected rabbits were capable of suppressing the response to concanavalin A. Although immune complexes were regularly present in suppressive sera and tissue extracts, additional experiments in which both direct and indirect approaches were used indicated that immune complexes were not responsible for the observed depression. Sequential stimulation studies, done with purified glycosaminoglycan materials obtained from suppressive sera and testicular fluids, and specific absorption studies suggested that this material blocks active sites on the lectin and merely prevents recognition of the mitogen by otherwise functionally active cells.

Animals↗
PubMed1982

Tolerant Staphylococcus aureus causing vertebral osteomyelitis.

Vertebral osteomyelitis due to Staphylococcus aureus was suppressed by not cured by optimal therapy with nafcillin sodium; cure eventually was achieved by treatment with cefazolin sodium and gentamicin sulfate. This is vivo result correlated with in vitro observations that showed that the infecting organism was inhibited but not killed by prolonged incubation with nafcillin or cefazolin; killing was readily achieved in vitro by adding subinhibitory concentrations of gentamicin. Bacterial tolerance in this case appeared to be responsible for the failure of vertebral osteomyelitis to be cured by accepted therapy with beta-lactam antibiotics.

Aged↗
PubMed1981

Haemophilus influenzae infections in adults: characterization of strains by serotypes, biotypes, and beta-lactamase production.

One hundred three cases of bacteremia or meningitis due to Haemophilus influenzae in adults were evaluated. Among 96 episodes of bacteremia, 60% were due to pneumonia and 15% to genital-related infections; 10% had no apparent source of infection. Of 42 isolates serotyped in routine fashion by slide agglutination, 79% were reported as type b. In contrast, of 45 isolates from the same interval with confirmed serotyping (usually by counterimmunoelectrophoresis), only 29% were type b and 64% were nontypable; 26% had been misidentified by routine slide agglutination. The majority (85%) of confirmed typable strains were biotype I. Four (40%) of 10 nontypable obstetrical isolates belonged to the relatively rare biotype IV. Only 2% of isolates were ampicillin-resistant, despite a high resistance rate among pediatric isolates in the same communities. When serotyping is carefully performed, nontypable organisms appear to be the major cause of invasive H. influenzae disease in adults.

Adult↗
PubMed1981

Evaluation of rosaramicin phosphate in treatment of experimental syphilis in rabbits.

The in vivo activity of rosaramicin phosphate in disseminated and localized Treponema pallidum infections in rabbits was compared with that of penicillin G benzathine. Rabbits were injected either intradermally or intravenously to establish infection. Groups of four animals each then received either two weekly injections of 200,000 U of penicillin G benzathine, injections of 12.5 or 25 mg of rosaramicin per kg of body weight twice a day for 10 days, or no antibiotic therapy. Treatment of the intradermal and intravenous infections was initiated on days 7 and 14 postinfection, respectively. With both infection models, striking differences were noted between the untreated control rabbits and the three groups receiving treatment; no discernible differences, however, were detected among any of the treated groups. Rabbits that had been infected intravenously did not develop disseminated lesions or orchitis after treatment, and chancres produced by intradermal infection regressed and healed rapidly after the initiation of therapy. Continued increases in treponemal and nontreponemal antibody titers posttreatment did not occur in any of the treated rabbits. Infectivity studies also suggested that the lymph nodes and testes of treated animals were free from infectious organisms. Overall, at the dosage regimens employed, both rosaramicin and penicillin G benzathine appeared to effect complete control of the experimental disease.

Animals↗
PubMed1981

Suppression of phagocytosis and chemotaxis by cell wall components of Staphylococcus aureus.

The ability of S. aureus to resist phagocytosis by polymorphonuclear leukocytes (PMN) is thought to be an important virulence factor for this microorganism. We have studied the effect of 3 major cell wall components of S. aureus, peptidoglycan, protein A, and teichoic acid, on PMN function. Phagocytosis and chemotaxis were both inhibited by prior incubation of PMN with peptidoglycan. This effect was dose- and time-related; incubation with as little as 2.5 micrograms/ml for 30 min produced a discernible suppressive effect. Suppression of PMN function was independent of the presence of human serum but was abolished by rabbit antiserum to peptidoglycan. Addition of peptidoglycan to PMN stimulated a prolonged chemiluminescence response that was greater when the peptidoglycan was first incubated in normal serum, perhaps reflection opsonization of this particulate material. Although protein A also suppressed phagocytic and chemotactic capabilities of PMN, this effect was observed only in the presence of serum and was eliminated by absorbing Ig. Centrifugation of the serum + protein A mixture showed that the suppressive effect was contained in the precipitated sediment. Complexes of Ig alone were not suppressive. Teichoic acid in concentrations less than or equal to 100 micrograms/ml had no adverse effect on PMN function. These studies describe ways in which peptidoglycan and protein A may interfere with phagocytosis and chemotaxis of human PMN, thus giving evidence for the role of these cell wall components as virulence factors.

Animals↗
PubMed1980

Disseminated strongyloidiasis. Diagnosis made by sputum examination.

Two immune-compromised patients had pulmonary and intestinal infection due to Strongyloides stercoralis. Diagnosis was facilitated in both cases when the parasites were found in the sputum. Treatment with thiabendazole appeared to eradicate the infection, but repeated follow-up examinations are needed because of the likelihood of relapse.

Feces↗
PubMed1980

Hypoglycemia as a manifestation of sepsis.

Hypoglycemia has rarely been described as a clinical sign of severe bacterial sepsis. We recently encountered nine patients in whom hypoglycemia (mean serum glucose of 22 mg/dl) was associated with overwhelming sepsis. Clinical disease in these patients included pneumonia and cellulitis; in three patients, no focus of infection was apparent. Altered mental status, metabolic acidosis, leukopenia, abnormal clotting studies and bacteremia were common features in these cases. In four patients, no cause for hypoglycemia other than sepsis was present. In five patients, another possible metabolic cause for hypoglycemia was present (alcoholism in four and chronic renal insufficiency in one) although none had been observed to be hypoglycemic on previous hospitalizations. Streptococcus pneumoniae (three cases) and Hemophilus influenzae, type b, (two cases) were the most common pathogens, and the over-all mortality was 67 per cent. The mechanism(s) for hypoglycemia with sepsis is not well defined. Depleted glycogen stores, impaired gluconeogenesis and increased peripheral glucose utilization may all be contributing factors. Incubation of bacteria in fresh blood at room temperature does not increase the normal rate of breakdown of glucose suggesting that the hypoglycemia occurs in vivo. Hypoglycemia is an important sign of overwhelming sepsis that may be more common than has previously been recognized.

Acidosis↗
PubMed1980

Bacterial adherence to pharyngeal cells during viral infection.

Adherence of bacteria to pharyngeal cells from patients with naturally acquired acute respiratory illness and from volunteers experimentally infected with influenza virus vaccine was studied. Increased adherence of Staphylococcus aureus was found in both groups. In addition, Haemophilus influenzae and Streptococcus pneumoniae type I adhered in increased numbers to cells from volunteers experimentally infected with influenza virus. Alterations in mucosal cells leading to increased bacterial adherence may play a role in the pathogenesis of suprainfection by these organisms in patients with viral respiratory diseases.

Adult↗
PubMed1980

Articular and skeletal infections caused by Pasteurella multocida.

Pasteurella multocida infections of joints and bones generally occur in individuals who have contact with cats or dogs. Osteomyelitis usually follows penetrating trauma such as an animal bite. Septic arthritis tends to occur in patients who have preexisting inflammatory joint disease, especially if a systemic condition which is known to predispose to infection is present. The principles of therapy for septic arthritis or osteomyelitis are no different from those which have been established for other infecting organisms. Although P multocida is susceptible in vitro to penicillin, treatment of septic arthritis with this drug is still associated with a slow therapeutic response.

Anti-Bacterial Agents↗
PubMed1980

Treatment of cellulitis with ceforanide.

Thirty-five patients with cellulitis were treated with ceforanide, 1 g every 12 h, intramuscularly. A good clinical response was observed in 33 cases. Drug failure in the remaining two patients was thought to be due to the lack of surgical debridement. Drug concentrations well in excess of inhibitory levels for Streptococcus pyogenes were generally present throughout the treatment period; although this was not true of ceforanide concentrations relative to inhibitory levels for Staphylococcus aureus, the clinical response in patients with staphylococcal infection still appeared to be entirely satisfactory. Killing of S. pyogenes by 5, 50, and 500X the minimum inhibitory concentration of ceforanide proceeded at the same rate in vitro as did killing by 5, 50, and 500X the minimum inhibitory concentration of penicillin.

Bacteria↗
PubMed1980

Detection of circulating immune complexes in the sera of rabbits with experimental syphilis: possible role in immunoregulation.

The in vivo and in vitro immunoglobulin G plaque-forming cell responses to sheep erythrocytes (SRBC) are nearly obliterated during disseminated syphilitic infection (3 to 8 weeks post-intravenous injection) in rabbits. Splenic and lymph node cells obtained from infected rabbits during this time period were capable of suppressing the normal in vitro responses of uninfected, SRBC-primed cells. Cell-free washings of cells from infected animals were also suppressive. This finding coupled with the fact that treatment of infected cells with proteolytic enzymes abrogated the suppressive effect constitute arguments against involvement of a specific suppressor cell population. The incidence of elevated levels of circulating immune complexes in the sera of rabbits with disseminated disease was also significantly different from that of uninfected controls or infected rabbits before the onset or after the regression of lesions. When added to cultures of lymphocytes from uninfected, SRBC-sensitized rabbits, sera containing complexes caused dose-related suppression of the in vitro immunoglobulin responses. Unlike immune complexes, no correlation was found between the presence of mucopolysaccharide materials and the stage of infection or the ability of serum to suppress the immunoglobulin responses to SRBC.

Animals↗