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Biomedical subjects

D M Musher

Publications and source records attributed to D M Musher.

At least 199 records · Page 11Linked to original sources

Hemophilus influenzae pneumonia in adults.

Hemophilus influenzae pneumonia was diagnosed in 41 adult patients based on cultures of blood, pleural fluid or transtracheal aspirate. Bacteremia occurred in all age groups, but was most frequent in patients over the age of 50 years with severe underlying pulmonary disease. Chest films usually demonstrated multisegmental or multilobar infiltrates without evidence of cavitation. Pleural involvement was evident in half of the patients, although empyema occurred infrequently. Mortality was almost always associated with serious underlying diseases and bacteremia. Encapsulated strains of H. influenzae (usually type B) were identified in 18 of 22 (82 per cent) patients. The use of transtracheal aspirations and the adoption of routine subculturing of blood cultures on chocolate agar appear to be important factors in our increased recognition of this disease.

Adolescent↗

Acetohydroxamic acid: clinical studies of a urease inhibitor in patients with staghorn renal calculi.

The hydrolysis of urea by the bacterial enzyme urease pathologically increase urinary ammonia, bicarbonate, carconate and alkalinity. These factors contribute to the formation of urinary stones and to the virulence of bacteria. Acetohydroxamic acid, a potent inhibitor of urease, has been administered to 23 patients with staghorn renal calculi and urea-splitting urinary infection. Urinary ammonia and alkalinity has been reduced in every patient. A dose of 1.0 gm. acetohydroxamic acid daily has been well tolerated and effective for 2 to 12 months, even in patients with impaired renal function.

Ammonia↗

Mitogenic activity of bacterial lipopolysaccharides in vivo: morphological and functinal characterization of responding cells.

The in vivo effect of bacterial lipopolysaccharides (LPS) on mouse spleen cell subpopulations was investigated. Intravenous administration of LPS resulted in marked enlargement of the spleen, accompanied by increased cellular proliferation and enhanced nucleated cell recoveries. At least two morphologically distinct cell types appeared to be targets for LPS. Polymorphonuclear leukocytes accumulated rapidly with a relatively minor degree of cell division. In contrast, a substantial proportion of splenic lymphocytes transformed into large lymphocytes and blast cells which actively incorporated [3H]thymidine. Proliferating cells were identified as bone marrow-derived (B) lymphocytes by their ability to form C3-dependent rosettes and to synthesize immunoglobulin. These cellular responses were not antigenically induced, since LPS derived from mutants lacking the polysaccharide moiety gave similar results. Thus, splenic B lymphocytes appear to interact and respond to LPS in vivo in the same manner as observed in vitro. These data suggest that the capacity of LPS to directly activate B lymphocytes, initiate cellular proliferation, and induce immunoglobulin production by bone marrow-derived cells in vivo may contribute to its adjuvant activity.

Animals↗

Strain-dependent cytotoxic effects of endotoxin for mouse peritoneal macrophages.

The cytotoxic effects of bacterial lipopolysaccharides (LPS) on mouse leukocytes have been examined in vivo and in vitro. Intraperitoneal injection of LPS into C57BL/6 mice greatly reduced the recovery of mononuclear cells; LPS was cytotoxic for macrophages, but had a mitogenic effect on lymphocytes. Similar effects of LPS on peritoneal leukocytes were observed in vitro. When monolayers of adherent peritoneal cells were studied in vitro, cytotoxicity was also observed, suggesting that the effect of LPS on macrophages is direct and does not require participation by lymphocytes. Entirely different results were obtained when peritoneal macrophages from LPS-resistant C3H/HeJ mice were studied. LPS failed to activate lymphocytes and was not cytotoxic for macrophages in vitro or in vivo. The effect of LPS on polymorphonuclear leukocytes appeared to be the same in all mouse stains studied. Lipid A was shown to be the most biologically active portion of the LPS molecule. Whereas polysaccharide-deficient endotoxins extracted from rough mutants of Salmonella typhimurium were cytotoxic for macrophages in vitro, polysaccharides that lacked esterified fatty acids did not exhibit this activity. Since LPS may mediate its effects through affinity for mammalian cell membranes, the cellular unresponsiveness of C3H/H3J mice to LPS may reflect an inability of cells from LPS-resistant strains to interact with LPS at the membrane level.

Animals↗

Percutaneous drainage of lung abscess.

The availability of effective antimicrobial agents has greatly decreased the need for surgical intervention in patients who have a pyogenic lung abscess. We describe 3 patients with lung abscesses caused by gram-negative bacteria who failed to respond to medical treatment and who were believed to be unable to withstand lobectomy. Percutaneous insertion of a drainage tube directly into the abscess brought about a dramatic clinical response, with prompt closure of the cavity. This procedure provides an alternative to thoracotomy and lobectomy in treating lung abscesses that fail to respond to medical therapy.

Drainage↗

Altered immune responsiveness associated with experimental syphilis in the rabbit: elevated IgM and depressed IgG responses to sheep erythrocytes.

Generalized suppression of immunoglobulin G (IgG) synthesis detectable by depressed responses to heterologous antigens may be a mechanism by which certain parasites evade host defenses and establish chronic infections. To determine if such a mechanism occurs in syphilis, rabbits were infected with Treponema pallidum, and at weekly intervals thereafter these rabbits and uninfected controls were sensitized with SRBC. Seven days later the number of antibody-forming cells present in the spleen was determined by the Jerne plaque technique. After a transient suppression in the 1st week, IgM-PFC were elevated from up to 7 weeks after infection. The IgG response to SRBC was depressed early in infection and continued to decline to less than one-tenth of control levels over the next few weeks persisting throughout overt infection and returning to normal by the end of 2 months. IgG-PFC, and 2-ME-resistant hemagglutinins and hemolysins were also significantly depressed in infected rabbits after two immunizing doses of SRBC. These results suggest that the depressed IgG response caused by syphilitic infection may enable treponemes to evade host immunity by interfering with immunoregulatory mechanisms.

Animals↗

Candida tropicalis arthritis - assessment of amphotericin B therapy.

A 28 year old male heroin addict developed Candida tropicalis infection of the knee joint in association with candidemia. Assessment of amphotericin B therapy was facilitated by the determination of serum and synovial fluid amphotericin B concentrations using a radiometric bio-assay method. The results indicate that adequate synovial fluid drug levels were achieved with intravenous systemic therapy.

Adult↗

Disk diffusion susceptibility testing of Nocardia species.

The effectiveness of 13 antimicrobial agents against 51 clinical isolates of Nocardia was determined with use of agar dilutions and disk diffusion method. Amikacin inhibited less than 90% of isolates and, like the other aminoglycosides, showed good correlation between minimal inhibitory concentrations and sizes of zones of inhibition around the disks. Both sulfisoxazole and trimethoprim-sulfamethoxazole were very active, although they required a 2- to 3-log lower inoculum for demonstration of susceptibility. Results with the two sulfa disks were variable, but they did allow distinction between sensitive and intermediate strains. All of the isolates of Nocardia were inhibited by 6.3 microng of minocycline; however, the degree of susceptibility could not be determined by zone diameters. Only two-thirds of these clinical isolates of Nocardia grew rapidly enough to be assayed by either susceptibility method.

Anti-Bacterial Agents↗

Emergence of variant forms of Staphylococcus aureus after exposure to gentamicin and infectivity of the variants in experimental animals.

Exposure of a large inoculum of Staphylococcus aureus in vitro to concentrations of gentamicin that exceeded the minimal bactericidal concentration regularly resulted in the emergence of aminoglycoside-resistant bacterial variants. Variants lacked typical properties that are associated with S. aureus: they produced small, nonhemolytic colonies that were mostly coagulase-, deoxyribonuclease-, and mannitol-negative. In some instances phage type also differed from that of the parent forms. Animal models of subcutaneous and intravenous infection were studied with use of parent and variant forms of S. aureus. Subcutaneous injection of variants into rats readily produced abscesses, and intravenous inoculation into mice caused pyelonephritis, although in each experimental model in which equivalent bacterial inocula were used, parents produced more extensive disease. These data show that variants of S. aureus cause infection in experimental animals, although these variants appear to be somewhat less virulent than the parents from which they are derived. Preliminary studies in our laboratory have also shown that gentamicin-resistant variants of gram-negative bacilli can be induced by a single in vitro exposure to gentamicin. The virulence of these organisms and their role in antibiotic-susceptibility patterns of hospital flora warrant further investigation.

Animals↗

Lack of effect of methenamine in suppression of, or prophylaxis against, chronic urinary infection.

Methenamine is frequently prescribed for patients who have chronic urinary infection to suppress bacterial growth during active infection or to prevent recurrence once an infection has been brought under control. We have examined the effect of methenamine mandelate and ascorbic acid on bacteriuria in para- and quadriplegics from a spinal cord unit. Patients with indwelling urinary catheters and those on a program of intermittent catheterization were included. No suppressive or prophylactic effect of this regimen was observed in any of our patients. Methenamine does not appear to be an effective antimicrobial agent in subjects who have an indwelling urinary catheter or in patients with spinal cord injury who are on intermittent catheterization. Since there appears to be reason to question the efficacy of methenamine in situations in which it is usually prescribed, evidence should be sought for a therapeutic effect in other cases. If no benefit is observed, the drug should not be used.

Ascorbic Acid↗

Inability of spleen cells from chancre-immune rabbits to confer immunity to challenge with Treponema pallidum.

Although several lines of evidence suggest that cellular immune mechanisms play a role in controlling infection due to Treponema pallidum, recent studies have shown that induction of acquired cellular resistance by antigenically unrelated organisms fails to protect rabbits against syphilitic infection, thereby casting doubt on this hypothesis. In the present paper we describe attempts to transfer immunity to syphilis by using spleen cells from chancre-immune rabbits. Intravenous infusion of 2 X 10(8) spleen lymphocytes was capable of transferring acquired cellular resistance to Listeria and delayed hypersensitivity to tuberculin. However, in eight separate experiments using outbred or inbred rabbits, 2 X 10(8) spleen cells from syphilis-immune animals failed to confer resistance to T. pallidum whether by intravenous or intradermal challenge. Mixing immune lymphocytes with treponemes immediately before intradermal inoculation also failed to confer resistance. Despite the fact that syphilitic infection stimulates cellular immune mechanisms and induces acquired cellular resistance to antigenically unrelated organisms, cellular immunity may not play an important role in immunity to syphilis.

Animals↗

Effect of sensitization with Propionibacterium acnes on the growth of Listeria monocytogenes and Treponema pallidum in rabbits.

Sensitization of rabbits with Propionibacterium acnes, a nonspecific stimulant of the reticuloendothelial system, was investigated as a means of enhancing resistance to Treponema pallidum. A single i.v. dose of P. acnes given 3 or 7 days before challenge with Listeria monocytogenes was capable of suppressing the growth of the heterologous organism, whereas a single i.v. dose 24 hr or 14 days before challenge was not. Reactivation via i.v. elicitation with P. acnes 14 days after sensitization (1 day before challenge) caused significant suppression of listerial growth in the major organs 30 hr after i.v. challenge. A series of similar experiments was designed with T. pallidum as the challenge organism. Sensitization and repetitive elicitation with P. acnes did not change the time of appearance or progression of syphilitic chancres after i.v or i.d. challenge. Injection of P. acnes into sites of intradermal T. pallidum challenge in previously sensitized rabbits also failed to alter the evolution of syphilitic lesions. These results suggest that macrophage activation does not alter the host's ability to suppress the growth of T. pallidum.

Animals↗

Quantitative urinalysis. Diagnosing urinary tract infection in men.

Using a hemocytometer, we determined the number of white blood cells (WBCs) per milliliter in uncentrifuged urine specimens. Uninfected urine usually contained less than or equal to 10(3) WBCs per milliliter, although up to 8 X 10(3) WBCs per milliliter were observed. Infected urine regularly contained greater than 10(4) WBCs per milliliter, and the mean WBC count per millimeter for urine from infected patients was 3.1 X 10(5). The absence of pyuria thus provides strong evidence against the presence of urinary tract infection. Similar results were obtained in patients who had indwelling catheters, suggesting that bacteriuria reflects the presence of infection rather than colonization. Valid data are easily obtainable by quantitative urinalysis of uncentrifuged urine specimens. There are obvious differences in WBCs per milliliter, with little overlap between infected and uninfected urine. This method of analysis should replace traditional means of counting WBCs per visual field in a centrifuged, resuspended urine sediment.

Adult↗