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Biomedical subjects

D T Durack

Publications and source records attributed to D T Durack.

At least 73 records · Page 4Linked to original sources
PubMed1985

Current issues in prevention of infective endocarditis.

Prevention of infective endocarditis continues to concern health care providers in many specialties. The well-known lack of primary clinical trials in this area is not expected to change. Therefore, the evolution of recommendations and practice must be based on theoretic considerations and continuing assessment of secondary sources of information. Recent developments include a report of 52 cases in which antibiotic prophylaxis for infective endocarditis was attempted but appeared to fail. Most of these patients had undergone dental procedures after oral penicillin prophylaxis, with subsequent development of streptococcal endocarditis. In two thirds, the organism was sensitive to the antibiotic used. Notably, the most common underlying cardiac lesion among these patients was mitral valve prolapse. However, two recent independent analyses have concluded that providing endocarditis prophylaxis for all patients with mitral valve prolapse during procedures that might cause bacteremia would not be cost-effective. This is primarily because mitral valve prolapse is common and endocarditis is relatively rare, resulting in an adverse risk-benefit ratio. Parenteral prophylaxis for mitral valve prolapse might even cause a net loss of life from anaphylaxis. On the other hand, for the individual patient or physician, the reassurance provided by attempted prophylaxis with oral penicillin can be purchased at low cost and low risk. Very few cases of infective endocarditis have been reported after gastrointestinal and other endoscopic procedures; most of these do not need antibiotic coverage. Prophylactic antibiotics should be restricted to those situations in which both the procedure and the underlying cardiac condition seem to pose significant risk, for example, endoscopic sclerotherapy of esophageal varices in patients with prosthetic heart valves. Newly revised recommendations have been issued by the Medical Letter, the American Heart Association, and the American Dental Association. These regimens are shorter and simpler than earlier versions.

Anti-Bacterial Agents↗
PubMed1985

Chemotactic activity of cerebrospinal fluid in experimental cryptococcal meningitis.

Cerebrospinal fluid from rabbits with chronic cryptococcal meningitis was tested for its chemotactic activity towards polymorphonuclear cells and monocytes. CSF chemotactic activity was present; it peaked 5-8 days after infection, coinciding with the time when the number of inflammatory cells in CSF was greatest. However, little chemotactic activity could be found in the early stages of infection, during the initial ingress of inflammatory cells. The chemotactic activity appeared to be host-derived, with characteristics consistent with lymphokine(s) or C5a. Treatment with cortisone significantly reduced the CSF chemotactic activity for both cell types; this reduction may contribute to the severe CSF leukopenia observed in cortisone-treated animals, which are unable to eradicate this yeast infection. Modulation of CSF chemotactic activity may be important to the success or failure of the host central nervous system response to Cryptococcus neoformans.

Animals↗
PubMed1985

Penetration of imidazoles and triazoles into cerebrospinal fluid of rabbits.

We studied the penetration of two imidazoles (ketoconazole and vibunazole) and two triazoles (itraconazole and UK-49,858) into cerebrospinal fluid (CSF) of rabbits with and without meningitis. There were wide differences in degree of penetration of these drugs into CSF, from less than 3% to 66% of simultaneous serum concentrations. UK-49,858, which has little protein-binding, penetrated freely while itraconazole, which is highly protein-bound, could not be detected in CSF. Intermediate concentrations of vibunazole and ketoconazole were found in CSF. Presence of meningeal inflammation modestly increased CSF concentrations of ketoconazole but had no significant effect on penetration of the other three drugs. The excellent penetration of UK-49,858 indicates that it has promise for treatment of CNS fungal infections.

Animals↗
PubMed1985

Comparison of amphotericin B and N-D-ornithyl amphotericin B methyl ester in experimental cryptococcal meningitis and Candida albicans endocarditis with pyelonephritis.

Amphotericin B and N-D-ornithyl amphotericin B methyl ester were compared for therapeutic efficacies against experimentally induced cryptococcal meningitis and Candida albicans endocarditis with pyelonephritis in rabbits. Antifungal activity of the two polyenes in vitro was similar for the yeasts used in these experiments. N-D-ornithyl amphotericin B methyl ester gave a slightly higher concentration in serum than amphotericin B did, but both drugs had similar elimination curves, and penetration into the cerebrospinal fluid was poor for both. Despite these similarities between the two polyenes, amphotericin B was much more effective than N-D-ornithyl amphotericin B methyl ester in the treatment of cryptococcal meningitis in rabbits. For C. albicans endocarditis, both polyenes had similar cure rates, but in vitro measurement of fungicidal activity in serum did not predict treatment outcome. For C. albicans pyelonephritis, both polyenes showed efficacy; because higher doses of the less toxic methyl ester could be used, it sterilized the urinary tract more often than amphotericin B. These studies indicate that in vivo and in vitro experiments may be needed to predict the results of treatment with polyenes.

Amphotericin B↗
PubMed1985

Effects of cyclosporine in experimental cryptococcal meningitis.

We studied the effects of cyclosporine on experimental cryptococcal meningitis. Like cortisone, cyclosporine depressed the highly effective defense mechanisms of normal rabbits against inoculated Cryptococcus neoformans, causing them to develop progressive, fatal cryptococcal meningitis. Unlike cortisone, which causes a striking reduction in leukocytes in cerebrospinal fluid, cyclosporine depressed mononuclear cell function rather than numbers. Interleukin 2, a primary target for the immunodepressive action of cyclosporine, appears to be of central importance in central nervous system defenses against cryptococci. The findings suggest that humans receiving cyclosporine are likely to suffer increased incidence of cryptococcal infection.

Animals↗
PubMed1985

Virulence of Cryptococcus neoformans. Regulation of capsule synthesis by carbon dioxide.

Cryptococcus neoformans is variably encapsulated in vitro, whereas in tissues it develops a large capsule. We observed that cells of a strain with thin capsules, when growing in a standard fungal culture medium, became heavily encapsulated when incubated in serum-free cell culture medium (Dulbecco's modified Eagle's medium [DME]). Capsule size was quantitated physically by measuring cell volume, and chemically by determining the content of a capsular monosaccharide, glucuronate. The CO2/HCO-3 couple stimulated capsule development, resulting in visible enlargement by 3 h after exposure to high CO2/HCO-3. The amount of capsule per cell was directly proportional to the total millimolar CO2/HCO-3 concentration between 24 and 2.4 mM at pH 7.35, but at constant PCO2 (40 torr) and varying [HCO-3], the cells were heavily encapsulated down to pH 6.8. Concentration of CO2/HCO-3 in the physiologic range increased elaboration of polysaccharide into the medium and slowed the cell generation time from 2 to 6 h. Four other first-passage clinical isolates were all heavily encapsulated in DME with CO2/HCO-3, but variably encapsulated in DME without CO2/HCO-3. Exposure of yeast to increased CO2/HCO-3 caused a marked reduction in complement-mediated phagocytosis by mouse macrophages. A stable clone was isolated which contained capsular polysaccharide, but lacked the CO2-inducible phenotype. This clone was avirulent for steroid-treated rabbits. Thus, the prevailing CO2 concentration in mammalian tissues may be one stimulus for capsular polysaccharide synthesis. This could serve as an adaptive mechanism favoring parasite survival in the host.

Animals↗
PubMed1984

Prevention of central nervous system infections in patients at risk.

Infections of the central nervous system in patients at risk are relatively uncommon when compared with pneumonia, bacteremia, and soft tissue infection. However, they carry serious morbidity and are frequently fatal. Each of the diverse conditions that can place a patient at risk for central nervous system infection is associated with a fairly predictable spectrum of etiologic organisms. Various forms of trauma (including blunt and penetrating injuries and neurosurgery, especially when a cerebrospinal fluid shunt is implanted) predispose to infection with common pathogenic bacteria. Defects of cellular immunity including congenital immune deficiencies, immunosuppressive drug therapy, leukemia, lymphoma, and the acquired immune deficiency syndrome are more likely to give rise to infection with a distinctive spectrum of opportunistic viruses, fungi, and protozoa. Other underlying conditions include sinus, ear, and mastoid infections, congenital heart disease, intrathoracic suppuration, endocarditis, and bacteremia, hypogammaglobulinemia, and complement deficiencies. Some preventive measures including vaccines, antibiotics, and surgical procedures are available. However, for many of these central nervous system infections, preventive measures are lacking or less effective than those for infections in other organs. In the future, opportunistic central nervous system infections will increase in frequency as the number of patients at risk continues to grow.

Anti-Bacterial Agents↗
PubMed1984

An experimental model for pyogenic liver abscess.

We have developed a reproducible small-animal model for pyogenic liver abscess, suitable for investigating diagnostic and therapeutic modalities. Male New Zealand white rabbits weighing 2-3 kg were anaesthetized and the liver exposed. Gentle pressure was applied with forceps to the right hepatic lobe. A suspension of 10(5) colony forming units (cfu) Escherichia coli plus Fusobacterium necrophorum (10(6) cfu) plus Bacteroides fragilis (10(6) cfu) was immediately injected into a mesenteric vein. Two weeks later a palpable mass (mean diameter 4 cm) had developed. Thick pus could be aspirated percutaneously. Necropsy revealed a single, but often multiloculated, abscess at the site of the previous trauma. Injection of E. coli alone did not produce any abscesses and B. fragilis alone only small abscesses, with low and variable frequency. Inoculation with F. necrophorum alone produced large abscesses, and a dose-response relationship was established. This is a simple and reliable small-animal model useful in studies of imaging techniques, antibiotic regimens and invasive treatments for pyogenic liver abscess.

Animals↗
PubMed1984

Single and multiple pyogenic liver abscesses. Natural history, diagnosis and treatment, with emphasis on percutaneous drainage.

The presenting features, modes of treatment and clinical course were reviewed for 55 patients with pyogenic liver abscess, seen at Duke University Medical Center over a 15-year period. Thirty-three patients had a solitary abscess and 22 had multiple abscesses. Most patients were between the ages of 40 and 60 years. Males predominated, 2.4:1. Major underlying conditions included biliary tract disease, malignancy and colonic disease. Eight patients, each with a solitary abscess, had no identifiable underlying condition. Symptoms and signs were nonspecific: fever, chills, focal abdominal tenderness and hepatomegaly were common. A raised serum alkaline phosphatase level was the most consistent abnormal laboratory finding. CT with contrast enhancement, radioisotope scanning and ultrasonography all accurately defined solitary hepatic abscesses. However, CT scan was more successful than other imaging techniques in detecting multiple abscesses. In seven patients the diagnosis was made only at laparotomy. Overall, a diagnosis of liver abscess was made in 50 living patients (91%). Microorganisms were recovered from pus and/or blood cultures of 44 patients (80%). Most common were enteric gram-negative facultative rods, anaerobic gram-negative rods, and microaerophilic streptococci. Single abscesses were more likely than multiple abscesses to contain more than one organism. All patients received antibiotics; the choice of antibiotic does not appear to be critical provided the regimen has a broad spectrum including activity against anaerobes. Surgical or percutaneous drainage was successful when attempted in all patients with a single abscess, but the outcome was less favorable in those with multiple abscesses. Percutaneous drainage is currently replacing open operative drainage as the method of choice. Overall mortality in patients with single abscesses was 15% (5/33) and in those with multiple abscesses 41% (9/22).

Adolescent↗
PubMed1984

Aspergillus infection of a permanent ventricular pacing lead.

Fungal infections of intracardiac pacemakers are extremely rare. We describe what appears to be the first reported case of Aspergillus infection of a permanent pacing lead and review the three reported cases of other fungal infections of pacemaker leads which we could find in the literature. These infections may be encountered more frequently as the number of permanent pacemakers implanted in elderly patients with underlying medical illnesses continues to increase.

Aged↗
PubMed1984

An experimental model for Naegleria fowleri-induced primary amebic meningoencephalitis in rabbits.

A new model was developed in rabbits for primary amebic meningoencephalitis, a rare disease caused by the free-living ameba, Naegleria fowleri. Naegleria fowleri was cultured in a liquid axenic medium, and then injected intracisternally into New Zealand White rabbits. Inocula of 10(3) or 10(5) trophozoites consistently produced a sanguinopurulent meningitis; duration of survival of rabbits was 57 or 45 hr, respectively. Counts of cells in cerebrospinal fluid were proportional to the size of inoculum used; white blood cell counts ranged from 30 to 1,055 cells/mm3, and red blood cell counts from five to 8,640 cells/mm3. Necropsies revealed severe basilar meningoencephalitis with extensive hemorrhagic necrosis and polymorphonuclear cell infiltration. Trophozoites of N. fowleri were seen within the meningeal exudate and the brain parenchyma. Potential applications of this model include studies of the host response to amebae in the CSF, evaluation of the optimal route of administration of amphotericin B, and in vivo studies of other chemotherapeutic agents that show in vitro efficacy.

Amebiasis↗
PubMed1983

Apparent failures of endocarditis prophylaxis. Analysis of 52 cases submitted to a national registry.

Fifty-two cases of apparent endocarditis prophylaxis failure were reported to a national registry established by the American Heart Association (AHA). Mitral valve prolapse was the single most common underlying cardiac lesion (17 cases, 33%), followed by various congenital abnormalities (15 cases, 29%) and rheumatic heart disease (11 cases, 21%). Ten patients (19%) had prosthetic valve endocarditis. Forty-eight cases (92%) occurred after a dental procedure. Symptoms began within two weeks after the procedure suspected to have caused endocarditis in 50% and within five weeks in 79%. Thirty-nine cases (75%) were caused by viridans streptococci and seven (14%) by Staphylococcus aureus. Most patients received oral penicillin as prophylaxis. Only six patients (12%) received regimens currently recommended by the AHA. In 27 (63%) of the 43 cases for which antimicrobial susceptibility data were available, the infecting microorganism was sensitive to the antibiotic(s) used for prophylaxis. After diagnosis of endocarditis, the prognosis for bacteriologic cure was good; 47 patients (90%) were cured, of whom seven underwent valve replacement. These data indicate that endocarditis prophylaxis failures may be more common than was previously believed and that failures occur even when the infecting organism is susceptible to the antibiotics used. Most antimicrobial regimens used in patients with prophylaxis failures did not conform to current recommendations.

Adolescent↗