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Biomedical subjects

D M Musher

Publications and source records attributed to D M Musher.

At least 217 records · Page 12Linked to original sources

Inhibition of the antibacterial activity of gentamicin by urine.

Urinary levels of antibiotics determine the outcome of treatment of most urinary tract infections. The antibacterial effect of gentamicin against Escherichia coli and Pseudomonas aeruginosa in urine was studied. With use of urinary constituents in concentrations normally found in human urine, it was shown that urine has an inhibitory effect that is dependent upon the acidity and total osmolality of the urine, as well as upon the presence of individual solutes. Up to 40 times as much gentamicin may be needed to prevent the growth of E. coli or P. aeruginosa in concentrated, acidic human urine as is required in broth. This inhibitory effect may be particularly important when urinary concentrations of gentamicin are reduced either because of a reduction in dosage or because of decreased excretion due to renal insufficiency.

Calcium Chloride↗

Further observations on the potentiation of the antibacterial effect of methenamine by acetohydroxamic acid.

The use of methenamine in the treatment of urinary tract infections due to Proteus species is limited by urine alkalinity. Acetohydroxamic acid, an inhibitor of urease, maintains acidity despite growth of Proteus in urine. Easily achievable concentrations of acetohydroxamic acid in vitro systems that simulated the dynamics of the urinary tract potentiated the antibacterial effect of methenamine against Proteus species. The combined use of a urease inhibitor and methenamine may be effective in the treatment of urinary infection caused by these organisms.

Ammonia↗

Immunologic mechanisms of infectious syphilis.

We believe that humoral and cellular immunity both are involved in the response of the host to infection with T. pallidum. A complex interaction between stimulation and suppression of cell-mediated immunity may be involved. This interaction may explain the unusual clinical course in which secondary syphilis waxes and wanes before culminating in immunity.

Animals↗

Vertebral osteomyelitis. Still a diagnostic pitfall.

Vertebral osteomyelitis is still a diagnostic problem. Nonspecific symptoms (low-grade fever, malaise, and weight loss) may dominate. Specific infections may be suggested by the history, and the diagnosis may be reinforced by a transient response to antibiotics. The patient may have symptoms resulting from a secondary paravertebral abscess. Even with fever, back pain, and point tenderness over the vertebral column, the correct diagnosis may not be considered. Predisposing conditions include drug addiction, instrumentation of the infected urinary tract, bacteremia from other causes, or previous back surgery. Diagnosis is made by roentgenographic studies and isolation of the causative organism from blood cultures or from the infected area. Staphylococcus aureus is the most common pathogen, although other microorganisms may be responsible. Intensive intravenous antibiotic treatment appears to be curative, without surgical debridement, external stabilization, or porlonged oral administration of antibiotics.

Adult↗

Dissolution of struvite urinary stones. Experimental studies in vitro.

Previous studies from our laboratory have shown that struvite crystals form primarily as a result of urease-induced alkalinity and supersaturation. In vitro perfusion of struvite crystals with undersaturated urine caused crystal dissolution. The investigations reported herein demonstrate complete dissolution of human struvite urinary stones during 6 weeks of perfusion in vitro with undersaturated human urine. Human hydroxyapatite stones perfused similarly underwent only slight dissolution. A glycoprotein precipitated as the stones dissolved; the pathogenic significance of the glycoprotein is unknown.

Apatites↗

The generation of formaldehyde from methenamine. Effect of urinary flow and residual volume.

The antimicrobial effect of methenamine in urine is dependent upon: (i) the rate of generation of formaldehyde; (ii) the concentration of formaldehyde achieved; and (iii) the duration of bacterial exposure to formaldehyde. Studies utilizing an in vitro model which simulates the dynamics of the urinary tract showed that bacteriostatic concentrations of formaldehyde (greater than or equal to 25 mug per ml) were obtained from attainable concentrations of methenamine at urine pH 5.7 to 5.85. Reduced urinary flow rates and large residual volumes increased formaldehyde concentrations and would appear to provide prolonged bacterial exposure to the formaldehyde.

Formaldehyde↗

Urease. The primary cause of infection-induced urinary stones.

Previous reports have suggested that urease-producing bacteria play a prominent role in the formation of infection-induced urinary stones. We have carried out crystalization experiments in vitro which show that bacterial urease alkalinizes urine, thereby causing: (i) supersaturation with respect to struvite and calcium phosphate; and (ii) formation of struvite and apatite crystals. Growth of Proteus in urea-free urine or in urine which contained a urease inhibitor did not cause alkalinization, supersaturation, or crystallization of struvite and apatite. Growth of Klebsiella, Escherichia coli, or Pseudomonas was not associated with significant alkalinization, supersaturation, or crystallization. Struvite and apatite crystals dissolved in Proteus-infected urine in which undersaturation was maintained by urease inhibition. Similar results in all experiments were obtained using human urine and a synthetic urine which was devoid of matrix, pyrophosphate, or other undefined solutes. Urease-induced supersaturation appears to be the primary cause of infection-induced urinary stones.

Bacteria↗

The diagnostic value of sputum culture in acute pneumonia.

In a prospective study of patients with acute pneumonia, the results of bacteriologic analysis of sputum, transtracheal aspirate (TA), and bronchial aspirate (BA) were compared. Streptococcus pneumoniae was grown from all three sources as the predominant organism in 13 of 16 cases; the remaining three patients had nonbacterial lung disease. These data support the traditional concept that culture of the sputum is highly reliable in providing a correct diagnosis in acute pneumonia.

Acute Disease↗

Acetohydroxamic acid. Potential use in urinary infection caused by urea-splitting bacteria.

Several lines of evidence suggest that bacterial urease is the primary cause of infection-induced urinary stones. The hydroxamate group of compounds are specific urease inhibitors. Of the cogeners studied, to dat, AHA (acetohydroxamic acid) appears to have the most pharmacologic potential. AHA is rapidly and completely absorbed from the gastrointestinal tract and is concentrated and excreted in the urine. In animals it appears to be relatively nontoxic. Although its toxicity in human beings has not been studied, its similarity to hydroxyurea suggests that reversible toxicity involving the gastrointestinal tract and the hematopoietic systems may result when high doses are administered. The only known metabolite of AHA is acetamide which is nontoxic and rapidly excreted in the urine. Pharmacologic use of AHA is expected to be practical and relatively safe. Use of AHA in patients with urinary infections caused by urea-splitting bacteria may reduce pathogenicity of the infecting organism and may lead to prevention and/or dissolution of stones commonly associated with such infections.

Acetamides↗

Role of urease in pyelonephritis resulting from urinary tract infection with Proteus.

The role of urease in induction of pyelonephritis was studied by treatment of proteus-infected rats with acetohydroxamic acid, a potent inhibitor of urease. Infection was produced by introduction of Proteus mirabilis into the bladder along with a zinc disk. Controls were treated identically but received no acetohydroxamic acid. The number of bacteria per milliliter of urine was the same in both groups. The number of bacteria in the kidneys and the extent of renal damage was much greater in controls. Common enterobacteraceal antigen was not detected in the renal parenchyma of rats treated with acetohydroxamic acid. Treatment with acetohydroxamic acid thus prevented invasion of and damage to kidney tissue without reduction of urinary infection. Thus new evidence was found that the invasive properties of Proteus in the urinary tract are dependent on alkalinization of urine by urease and the resulting damage to the renal epithelium.

Acute Disease↗

Effectiveness of achievable urinary concentrations of tetracyclines against "tetracycline-resistant" pathogenic bacteria.

Hospitalized patients with urinary tract infections caused by Pseudomonas aeruginosa or other bacterial pathogens are frequently treated with parenteral antibiotics such as gentamicin. Many of these organisms are shown by Kirby-Bauer disk sensitivity testing to be resistant to tetracycline. One hundred seventy-one such tetracycline-resistant bacterial isolates were studied; 84% were found to be sensitive to achievable urinary concentrations of tetracycline. Two patients with long-standing chronic urinary tract infection with Pseudomonas were treated with tetracycline for a year and a half with excellent results. In a pilot clinical trial, eight of 12 hospitalized patients with urinary tract infection were treated successfully with tetracycline without regard to disk sensitivity data. Institution of tetracycline as soon as the microscopic diagnosis of urinary tract infection is made might be an acceptable empiric approach to the treatment of urinary infection in hospitalized patients who do not show evidence of sepsis.

Bacteriuria↗

Lymphocyte transformation in syphilis: an in vitro correlate of immune suppression in vivo?

Suppression of cellular immunity during primary and secondary infection may explain, in part, the unusual clinical evolution of syphilis. We have previously shown that lymphocytes from normal subjects undergo blastic transformation when exposed in vitro to Treponema refringens. This response was suppressed in patients with syphilis. the suppression being unrelated to serum factors. In the present paper we studied lymphocyte response in vitro to T. refringens, T. reiter, and T. pallidum as well as to monilia and trychophytins. The response to these antigens was suppressed in patients with syphilis although the response to phytohemagglutinin. pokeweed mitogen, and streptolysin was normal. These data support the hypothesis that human infection with T. pallidum is followed by a complex interaction between cellular and humoral immunity, the former being suppressed in primary and secondary stages.

Antigens, Bacterial↗

New evidence for the non-infectivity of Treponema pallidum for mice.

We have recently shown that syphilitic rabbits are resistant to challenge with Listeria monocytogenes. This resistance was thought to reflect stimulation of cell-mediated immunity by active infection with Treponema pallidum. We now report data which show that the growth of Listeria was not suppressed in mice inoculated with T. pallidum. Re-inoculation with T, pallidum or with a large dose of an avirulent treponeme also failed to suppress the growth of Listeria. These results contrast with those obtained in rabbits and provide additional evidence that T. pallidum is not infective for the mouse.

Animals↗