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Biomedical subjects

S W Redding

Publications and source records attributed to S W Redding.

At least 19 recordsLinked to original sources

Coronary artery stents: review and patient-management recommendations.

BACKGROUND: Coronary artery stents are metallic scaffold devices that physically support narrowed coronary arteries to alleviate symptoms of ischemic coronary artery disease. They are placed during invasive procedures similar to that of percutaneous transluminal coronary angioplasty, and patients are maintained with antiplatelet medications to lessen the chances of stent stenosis. METHODS: The authors provide a brief overview of coronary artery stents and discuss the dental management of patients who have received stents. CONCLUSIONS: After stent placement, patients usually are maintained with antiplatelet regimens, which may necessitate choosing medications that do not potentiate their effects. Any discussion as to the possible need for antibiotic prophylaxis of patients with stents largely is missing from the literature. Recent literature, however, indicates that antibiotic prophylaxis, if required, may only be needed during the first few weeks after stent placement. CLINICAL IMPLICATIONS: Dental professionals should become knowledgeable about coronary artery stents. Although these devices have a higher success rate than other procedures in alleviating symptoms of ischemic coronary artery disease, some patients are still at risk of experiencing significant cardiac events.

American Hospital Association↗

Epidemiology of oropharyngeal Candida colonization and infection in patients receiving radiation for head and neck cancer.

Oral mucosal colonization and infection with Candida are common in patients receiving radiation therapy for head and neck cancer. Infection is marked by oral pain and/or burning and can lead to significant patient morbidity. The purpose of this study was to identify Candida strain diversity in this population by using a chromogenic medium, subculturing, molecular typing, and antifungal susceptibility testing of clinical isolates. These results were then correlated with clinical outcome in patients treated with fluconazole for infection. Specimens from 30 patients receiving radiation therapy for head and neck cancer were cultured weekly for Candida. Patients exhibiting clinical infection were treated with oral fluconazole. All isolates were plated on CHROMagar Candida and RPMI medium, subcultured, and submitted for antifungal susceptibility testing and molecular typing. Infections occurred in 27% of the patients and were predominantly due to Candida albicans (78%). Candida carriage occurred in 73% of patients and at 51% of patient visits. Yeasts other than C. albicans predominated in carriage, as they were isolated from 59% of patients and at 52% of patient visits. All infections responded clinically, and all isolates were susceptible to fluconazole. Molecular typing showed that most patients had similar strains throughout their radiation treatment. One patient, however, did show the acquisition of a new strain. With this high rate of infection (27%), prophylaxis to prevent infection should be evaluated for these patients.

Antifungal Agents↗

A randomized trial of continuous or intermittent therapy with fluconazole for oropharyngeal candidiasis in HIV-infected patients: clinical outcomes and development of fluconazole resistance.

PURPOSE: The effects of continuous or intermittent therapy with fluconazole on the recurrence of and the development of fluconazole resistance are not known. PATIENTS AND METHODS: We studied human immunodeficiency virus (HIV)-positive patients with CD4 cell count <350 x 10(6)/L and oropharyngeal candidiasis in a prospective, randomized study. After initial treatment, 20 patients (16 of whom completed 3 months of follow-up) received continuous fluconazole at 200 mg/day, and 48 patients (28 of whom completed follow-up) received intermittent therapy at the time of symptomatic relapses. Oral samples were obtained weekly during episodes of infection and quarterly as surveillance cultures. Development of resistance was defined as a fourfold rise in minimum inhibitory concentration (MIC) to at least 16 microg/mL from the initial culture in the same species, the emergence of new, resistant (MIC > or =16 microg/mL) species, or a significant increase in the proportion of resistant isolates. RESULTS: During a mean follow-up of 11 months, median annual relapse rates were lower in patients on continuous therapy (0 episodes/year) than in patients on intermittent therapy (4.1 episodes/year; P <0.001). Sterile cultures were seen in 6 of 16 (38%) patients on continuous therapy compared with 3 of 28 (11%) on intermittent therapy (P = 0.04). Microbiological resistance developed in 9 of 16 (56%) patients on continuous treatment, compared with 13 of 28 (46%) on intermittent treatment (P = 0.75). However, despite isolates with increased MICs, 42 of 44 patients responded to fluconazole in doses up to 800 mg/day. CONCLUSIONS: In patients with frequent recurrences, continuous suppressive therapy significantly reduced relapses and colonization. Resistance occurred with both continuous and intermittent therapy; however, therapeutic responses were excellent.

AIDS-Related Opportunistic Infections↗

Treatment of oral chronic graft-versus-host disease with PUVA therapy: case report and literature review.

Chronic graft-versus-host disease commonly appears with oral manifestations subsequent to allogeneic bone marrow transplantation. These manifestations include leukoplakia, mucosal atrophy, erythema, ulcers, and xerostomia. Some lesions are resistant to treatment with immunosuppressive medications. Ultraviolet A irradiation therapy with oral psoralen has been shown to be effective in treating these resistant lesions. This article presents a review of the literature and a case report.

Administration, Oral↗

Clinical evaluation and microbiology of oropharyngeal infection due to fluconazole-resistant Candida in human immunodeficiency virus-infected patients.

Signs and symptoms of oropharyngeal candidiasis (OPC) were correlated with microbiology and clinical response to fluconazole in a cohort of patients with advanced human immunodeficiency virus (HIV) infection and recurrent OPC. Sixty-four HIV-infected patients with a median CD4 cell count of < 50/mm3 (range, 3-318/mm3) who presented with OPC were enrolled in a longitudinal study. Specimens for cultures were taken weekly until clinical resolution. Therapy with fluconazole was increased weekly as required to a maximum daily dose of 800 mg until resolution of symptoms and oral lesions. Resistant or dose-dependent susceptible yeasts, defined as a minimum inhibitory concentration of > or = 16 micrograms/mL, were detected in 48 (31%) of 155 episodes. Clinical resolution with fluconazole therapy occurred in 107 (100%) of 107 episodes with susceptible yeasts vs. 44 (92%) of 48 episodes with resistant or dose-dependent susceptible strains (P = .008). Patients from whom fluconazole-resistant yeasts were isolated required longer courses of therapy and higher doses of fluconazole for response, but overall, excellent responses to fluconazole were seen in patients with advanced HIV infection.

AIDS-Related Opportunistic Infections↗

Interpretation of trailing endpoints in antifungal susceptibility testing by the National Committee for Clinical Laboratory Standards method.

Trailing endpoints remain a problem in antifungal susceptibility testing using the National Committee for Clinical Laboratory Standards (NCCLS) method. For isolates for which trailing endpoints are found, MICs of < or = 1 microg/ml at 24 h and of > 64 microg/ml at 48 h are usually observed. In a study of human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis, we identified three patients with multiple serial isolates for which trailing endpoints were observed with fluconazole. At 24 h, MICs were generally < or = 1 microg/ml by both broth macro- and microdilution methods. However, at 48 h, MICs were > 64 microg/ml, while the organism remained susceptible by agar dilution testing with fluconazole. Most episodes of oropharyngeal candidiasis with trailing-endpoint isolates responded to doses of fluconazole as low as 100 mg/day. Two patients had both susceptible and trailing-endpoint isolates by NCCLS broth macro- and microdilution testing; these isolates were found to be the same strain by pulsed-field gel electrophoresis using restriction fragment length polymorphisms. Another patient had two different strains, one for which trailing endpoints were observed and one which was susceptible at 48 h. Trailing endpoints may be seen with selected isolates of a strain or may be a characteristic finding for most or all isolates of a strain. In addition, with isolates for which trailing endpoints are observed, reading the endpoint for the NCCLS method at 24 h may be more appropriate.

Antifungal Agents↗

Fluconazole disk diffusion susceptibility testing of Candida species.

We describe a simple procedure for detecting fluconazole-resistant yeasts by a disk diffusion method. Forty clinical Candida sp. isolates were tested on RPMI-glucose agar with either 25- or 50-microgram fluconazole disks. With 25-microgram disks, zones of inhibition of >/=20 mm at 24 h accurately identified 29 of 29 isolates for which MICs were </=8 microgram/ml, and with 50-microgram disks, zones of >/=27 mm identified 28 of 29 such isolates. All 11 isolates for which MICs were >8 microgram/ml were identified by using either disk. Disk diffusion may be a useful screening method for clinical microbiology laboratories.

AIDS-Related Opportunistic Infections↗

Dental management and treatment of xerostomic patients.

Saliva is extremely important for the health and comfort of the oral cavity. Diminution in salivary flow is accompanied by a plethora of problems. A salivary flow inadequate to protect the oral cavity may be an occult condition. Dentists should evaluate those patients presenting with a high incidence or increased incidence of dental caries for a decreased salivary flow. We have presented diagnostic aids, management techniques and treatment modalities for these patients.

Antifungal Agents↗

Stable azole drug resistance associated with a substrain of Candida albicans from an HIV-infected patient.

Oral candidiasis is one of the earliest and most frequent complications of a failing immune system in HIV-infected individuals. For several years, oral candidiasis has been treated effectively with azole drugs, the one most frequently used is fluconazole. Unfortunately, extensive use of the drug for treatment and prophylaxis has led to treatment failure in an increasing number of patients. In most of these cases, strains of C. albicans isolated from the infection are less susceptible to fluconazole. The development of azole resistance in strains of C. albicans has been studied biochemically and more recently with molecular techniques. One excellent example of the development of azole resistance in C. albicans has been documented in a series of 17 C. albicans isolates from a single patient over a 2-year period. During this time, the patient experienced 14 episodes of oral candidiasis and was treated with increasing doses of fluconazole. Molecular and biochemical analyses confirms that the isolates are the same strain of C. albicans and that the resistance in these isolates is stable over 600 generations, suggesting that the changes in this strain are genetic in nature. In addition, the development of resistance is correlated with the identification of a substrain or variant of the original strain, as identified by restriction fragment length polymorphism (RFLP) analysis with the moderately repetitive probe, Ca3. The analysis of this series of isolates demonstrates that azole drug resistance is associated with several small genetic changes, each of which contributes to the overall resistance of the strain. Clearly, continual use of azole drugs by a patient can select for genetic changes that render oral candidiasis refractory to treatment.

AIDS-Related Opportunistic Infections↗

Variations in fluconazole susceptibility and DNA subtyping of multiple Candida albicans colonies from patients with AIDS and oral candidiasis suffering one or more episodes of infection.

Five Candida albicans colonies from each infection in AIDS patients receiving fluconazole therapy for oropharyngeal candidiasis over a 2-year period were evaluated by antifungal susceptibility testing and DNA subtyping, and the results were correlated with clinical response to determine the occurrence of clinically significant selection of more-resistant C. albicans over multiple infections. A total of 534 C. albicans isolates were obtained from 38 patients who exhibited 84 episodes of infection. Antifungal susceptibility testing revealed that the MICs for 93% of the isolates were < or = 8.0 microg/ml and the MICs for 7% of the isolates were > or = 64 microg/ml. DNA subtyping revealed 70 different subtypes, with 78% of patients with one infection exhibiting one DNA subtype and 80% of patients with more than one infection exhibiting multiple DNA subtypes. Also, patients who had multiple infections had lower CD4 counts than those with single infections. Differences between the single-infection group and the multiple-infection group regarding the number of DNA subtypes and CD4 counts were both statistically significant. Of the 74 evaluable infections all were successfully treated with regular-dose (100-mg/day) fluconazole, except for three patients who ultimately responded to higher-dose fluconazole. Only one patient may have shown clinically significant selection of a more-resistant C. albicans strain over multiple courses of treatment. Interestingly, MICs reached only 8.0 microg/ml, even though doses of 400 mg of fluconazole were necessary for clinical cure.

AIDS-Related Opportunistic Infections↗

Detection and significance of fluconazole resistance in oropharyngeal candidiasis in human immunodeficiency virus-infected patients.

The epidemiology and clinical significance of fluconazole resistance were assessed in a cohort of advanced human immunodeficiency virus (HIV)-infected patients with recurrent oropharyngeal candidiasis. Fifty patients were prospectively evaluated using a novel method of detecting fluconazole resistance with chromogenic media containing fluconazole; results were confirmed with macrobroth testing. Resistant yeasts, defined as MICs > or = 8 micrograms/mL, were detected in 16 (32%) of 50 patients: 7 (14%) had resistant Candida albicans, 7 (14%) had resistant non-C. albicans yeast, and 2 (4%) had mixed resistant yeasts. MICs were > or = 32 in 11 of 16 isolates. Previous fluconazole use and severe immunosuppression were risk factors for resistance. However, 5 of 26 patients had resistant isolates with no prior fluconazole use, and all were severely immunosuppressed. Despite the high prevalence of resistance, 48 patients clinically responded to fluconazole. Fluconazole-resistant C. albicans and non-C. albicans yeast infections are common in patients with advanced immunodeficiency, but clinical efficacy of fluconazole remains high.

AIDS-Related Opportunistic Infections↗

Simple method for detecting fluconazole-resistant yeasts with chromogenic agar.

A method for detecting fluconazole-resistant yeasts was developed that uses chromogenic agar containing fluconazole. Yeasts were plated on media with fluconazole at 0, 8, and 16 micrograms/ml. On media without fluconazole, normal growth of susceptible yeasts (defined as those having a fluconazole MIC of < 8 micrograms/ml) was detected, while fluconazole-containing media suppressed susceptible strains and normal colonies of resistant yeasts (fluconazole MICs of > or = 8 micrograms/ml) were detected. This method was used to screen for resistance in oropharyngeal candidiasis. Isolates having fluconazole MICs of > or = 8 micrograms/ml and < 8 micrograms/ml were correctly predicted in 43 of 45 cultures and 115 of 116 cultures, respectively. This screening method appears to be rapid and sensitive for detection of fluconazole-resistant yeasts.

Agar↗

PGY1: what is it and why is it important?

The interest in a year of additional training for the practice of dentistry has grown over the past fifteen years. Debates at national conferences and careful study by committees of professional organizations led to the recommendation that over the next five to ten year period the profession should move toward creating a postgraduate experience for each graduate prior to independent practice. While study of this issue will undoubtedly continue, it behooves us to proceed with the process of expanding the number of postgraduate positions, first, to meet the demand by graduating students who are voluntarily selecting a year of additional training, and later, so we are at a position to fully consider such a year as mandatory for independent practice. If we use the next five to ten years productively, we can create an environment where the public and the graduates will benefit from this additional year of training.

Accreditation↗

Variations in fluconazole susceptibility and electrophoretic karyotype among oral isolates of Candida albicans from patients with AIDS and oral candidiasis.

DNA subtyping by pulsed-field gel electrophoresis and in vitro susceptibility testing were used to study strain variation and fluconazole resistance in Candida albicans isolates from patients with AIDS undergoing azole (fluconazole and clotrimazole) therapy for oropharyngeal candidiasis. A total of 29 patients suffered 71 episodes of oropharyngeal candidiasis. Overall, 121 isolates of C. albicans recovered throughout the course of treatment of each infection were available for further characterization. DNA subtyping revealed a total of 61 different DNA subtypes. In vitro susceptibility testing of the 121 isolates by using proposed standard methods of the National Committee for Clinical Laboratory Standards revealed MICs of fluconazole ranging from < or = 0.125 to > 64 micrograms/ml. The MIC for 50% of isolates tested was 0.25 microgram/ml, and the MIC for 90% of isolates tested was 8.0 micrograms/ml. MICs were > or = 64 micrograms/ml for only 7.4% of the isolates tested. The majority (62%) of the patients with oropharyngeal candidiasis and undergoing azole therapy were infected or colonized with more than one DNA subtype, and the introduction or selection of strains with a more resistant DNA subtype during the course of fluconazole therapy was not uncommon. With one exception, this did not appear to have an adverse effect on clinical outcome. In contrast, for patients with AIDS and oropharyngeal candidiasis infected with a single DNA subtype of C. albicans, an increase in fluconazole MICs for the infecting strain was rarely demonstrated over the course of therapy.

Acquired Immunodeficiency Syndrome↗

Radiation-induced increased platelet-activating factor activity in mixed saliva.

BACKGROUND: Platelet-activating factor (PAF), a family of structurally-related phospholipid mediators of inflammation, is present in normal human mixed saliva; however, its role in oral biology and the homeostasis of oral host defense mechanisms remains to be established. EXPERIMENTAL DESIGN: The current study was designed to evaluate the salivary levels of PAF in patients with oral mucositis that developed as a complication of head and neck irradiation for oral cancer. PAF activity was assessed in platelet bioassay and expressed relative to the activity of authentic PAF, 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16:0-AGEPC). RESULTS: A significant increase in salivary PAF levels was observed in patients with mucositis (47,032 +/- 12,731 C16:0-AGEPC fmole equivalents/ml of saliva, mean +/- SE, N = 7) as compared with normal subjects (5,568 +/- 1,135 C16:0-AGEPC fmole equivalents/ml of saliva, N = 27). Phospholipid fractionation of the PAF isolated from the saliva of patients with mucositis by reverse phase high performance liquid chromatography revealed a single peak of activity that corresponded with the elution profile of C16:0-AGEPC, the most biologically active molecular species of PAF. In contrast, the PAF isolated from normal human mixed saliva contained multiple molecular species of PAF. CONCLUSIONS: These results suggest that this potent phospholipid inflammatory mediator may play a role in the inflammation and tissue injury associated with mucositis resulting from radiation treatment for oral cancer.

Humans↗