PubMed Health⌕ Search

Biomedical subjects

Jack D Sobel

Publications and source records attributed to Jack D Sobel.

At least 19 recordsLinked to original sources
PubMed2006

The VI-SENSE-vaginal discharge self-test to facilitate management of vaginal symptoms.

OBJECTIVE: This study was undertaken to evaluate a diagnostic panty liner (VI-SENSE) (Common Sense, Caesarea, Israel) developed to facilitate diagnosis of vaginal infections by detecting disordered acidity level. STUDY DESIGN: Five hundred sixteen women with vulvovaginal symptoms were enrolled. Final clinical diagnosis included Amsel criteria, Gram stain analysis, pH determination, and Trichomonas vaginalis and Candida culture. VI-SENSE strip color status estimated by patients was compared with clinical diagnosis and pH measurement by using nitrazine paper. Statistical analysis included sensitivity and specificity calculations. RESULTS: The VI-SENSE test was positive in 226 of 249 patients (90.8%) with bacterial vaginosis or trichomoniasis. Nitrazine pH paper revealed elevated pH in 165 (66.5%) and the amine test was positive in 160 (64.3%) patients. The VI-SENSE test was negative in 217 of 267 patients (81.3%) without trichomoniasis or bacterial vaginosis. The VI-SENSE was positive in 85 of 92 women (92%), with mixed vaginal infection including Candida and bacterial vaginosis or trichomoniasis. Amine test, nitrazine pH paper and physician diagnosis relying only on speculum examination were inferior and positive in only 65 (70%), 59 (64%), and 66 (72%) patients, respectively. CONCLUSION: The VI-SENSE test was found to be superior to traditional individual tests in facilitating preliminary diagnosis of vaginal infections.

Adult↗
PubMed2006

Anidulafungin: a novel echinocandin.

Until recently, the treatment available for serious fungal infections was composed of amphotericin B and azoles, and each class demonstrated significant limitations. Echinocandins are a new class of drugs that have shown promising results in treating a variety of fungal infections. Of these, anidulafungin is a novel echinocandin that appears to have several advantages over existing antifungals. It is unique because it slowly degrades in humans, undergoing a process of biotransformation rather than being metabolized. It has potent in vitro activity against Aspergillus and Candida species, including those resistant to fluconazole or amphotericin B. Results of several clinical trials indicate that anidulafungin is effective in treating esophageal candidiasis, including azole-refractory disease. The results of a recent study comparing fluconazole versus anidulafungin demonstrated the superiority of anidulafungin in the treatment of candidemia and invasive candidiasis (IC). Studies evaluating the concomitant use of anidulafungin and either amphotericin B, voriconazole, or cyclosporine did not demonstrate significant drug-drug interactions or adverse events. To date, anidulafungin appears to have an excellent safety profile. On the basis of early clinical experience, it appears that anidulafungin will be a valuable asset in the management of serious and difficult-to-treat fungal infections.

Anidulafungin↗
PubMed2006

Suppressive antibacterial therapy with 0.75% metronidazole vaginal gel to prevent recurrent bacterial vaginosis.

OBJECTIVE: Efficacy study of suppressive vaginal metronidazole in reducing recurrent symptomatic episodes of bacterial vaginosis. STUDY DESIGN: Multicenter prospective study with initial 10-day open-label metronidazole gel in which asymptomatic responders randomly assigned to receive twice weekly metronidazole vaginal gel or placebo for 16 weeks and off therapy for 12 weeks. RESULTS: Of 157 eligible women with recurrent bacterial vaginosis, 112 of 127 returning evaluable women (88.2%) responded clinically and were randomly assigned. During suppressive therapy, recurrent bacterial vaginosis occurred in 13 women (25.5%) receiving metronidazole and 26 (59.1%) receiving placebo (MITT analysis, relative risk [RR] 0.43, CI = 0.25-0.73, P = .001). During the entire 28-week follow-up, recurrence occurred in 26 (51.0%) on treatment compared with 33 (75%) on placebo (RR 0.68, CI = 0.49-0.93, P = .02). Probability for remaining cured was 70% for metronidazole compared with 39% on placebo, which declined to 34% and 18%, respectively, by 28 weeks follow-up. Adverse effects were uncommon; however, secondary vaginal candidiasis occurred significantly more often in metronidazole-treated women (P = .02). CONCLUSION: Suppressive therapy with twice-weekly metronidazole gel achieves a significant reduction in the recurrence rate of bacterial vaginosis; however, secondary vaginal candidiasis is common.

Administration, Intravaginal↗
PubMed2006

The emergence of non-albicans Candida species as causes of invasive candidiasis and candidemia.

The last three decades have seen an expanding pool of high-risk patients susceptible to the opportunistic pathogen Candida. Accordingly, a dramatic increase in nosocomial blood stream infections (BSIs) due to Candida spp has been reported throughout the world, starting in tertiary care centers and spreading to community hospitals. This absolute increase in Candida BSIs was accompanied by both an absolute and then a proportional increase in invasive infection caused by reduced fluconazole-susceptible non-albicans Candida spp. Currently, the incidence trend of BSI has stabilized, and Candida albicans remains the most common species causing fungal BSI. Clinicians must be aware of the importance and implications of non-albicans Candida spp when selecting antifungal drugs, although most studies have not shown significant outcome differences with use of the various antifungal classes.

Journal Article↗
PubMed2006

Management of recurrent vulvovaginal candidiasis: unresolved issues.

The introduction and widespread use of long-term maintenance suppressive fluconazole prophylaxis for recurrent vulvovaginal candidiasis (RVVC) has improved the quality of life for thousands of women worldwide. Moreover, the regimen is no longer expensive, and it is safe and well tolerated. However, the regimen frequently fails to cure the condition and serves only as an effective control measure in many cases. Moreover, some women are unable to tolerate the regimen, and new curative approaches are needed. This review presents the limitations of this suppressive regimen and a discussion of the possible reasons for these limitations and failure to cure. Also, the rationale for new drug development is reviewed here.

Journal Article↗
PubMed2006

Design of clinical trials of empiric antifungal therapy in patients with persistent febrile neutropenia: considerations and critiques.

Febrile neutropenic patients who receive antibiotics are at risk for fungal infections. This risk increases greatly with the length and severity of neutropenia. Because diagnostic tests for fungal infections lack sensitivity and specificity and because established fungal infections are associated with poor outcomes, empiric antifungal therapy is frequently given to patients with fever that persists despite antibacterial therapy. Early trials of empiric amphotericin B showed reductions in the number of invasive fungal infections and in related morbidity and mortality. However, as a result of infusion-related and renal adverse effects of amphotericin B, newer agents, such as lipid formulations of amphotericin B, extended-spectrum azoles, and echinocandins, have been developed. Although these alternatives have been associated with decreased toxicity, improved efficacy has not been clearly demonstrated. Although empiric antifungal therapy can prevent undetected breakthrough infections and morbidity associated with many fungal infections, its shortcomings include overtreatment, toxicity, and increased costs of unnecessary treatment. Recent studies have highlighted several questions in trial design and data interpretation. For example, what is the appropriate study design? Who should be enrolled in studies of empiric antifungal therapy? How should successful therapy be defined? These issues are reviewed to determine whether new antifungal agents should be evaluated for empiric use in patients with fever and neutropenia.

Amphotericin B↗
PubMed2006

Vulvodynia: a state-of-the-art consensus on definitions, diagnosis and management.

Vulvodynia is a chronic pain syndrome affecting up to 18% of the female population. Despite its high prevalence and associated distress, the etiology, diagnosis and clinical management of the disorder have not been clearly delineated. This "white paper" describes the findings and recommendations of a consensus conference panel based on a comprehensive review of the published literature on vulvodynia in addition to expert presentations on research findings and clinical management approaches. The consensus panel also identified key topics and issues forfurther research, including the role of inflammatory mechanisms and genetic factors and psychosexual contributors.

Biomedical Research↗
PubMed2005

A randomized study of the use of fluconazole in continuous versus episodic therapy in patients with advanced HIV infection and a history of oropharyngeal candidiasis: AIDS Clinical Trials Group Study 323/Mycoses Study Group Study 40.

BACKGROUND: In human immunodeficiency virus (HIV)-infected patients, fluconazole prophylaxis is associated with reductions in the rate of fungal infection. However, concerns exist with regard to the use of fluconazole prophylaxis and the risk of development of fluconazole treatment-refractory infections. METHODS: We performed a randomized, open-label trial that compared oral fluconazole given continuously (200 mg 3 times weekly; the "continuous fluconazole arm") with fluconazole that was provided only for episodes of orophayngeal candidiasis (OPC) or esophageal candidiasis (EC) (the "episodic fluconazole arm") in HIV-infected persons with CD4+ T cell counts of <150 cells/mm3 and a history of OPC. The primary study end point was the time to development of fluconazole-refractory OPC or EC, which was defined as lack of response to 200 mg fluconazole given daily for 14 or 21 days, respectively. RESULTS: A total of 413 subjects were randomized to receive continuous fluconazole, and 416 were randomized to receive episodic fluconazole. After 42 months, 17 subjects (4.1%) in the continuous fluconazole arm developed fluconazole-refractory OPC or EC infections, compared with 18 subjects (4.3%) in the episodic fluconazole arm, with no difference between treatment arms with regard to the time to development of a fluconazole-refractory infection within 24 months (P=.88, by log-rank test) or before the end of the study (P=.97, by the log-rank test). Continuous fluconazole therapy was associated with fewer cases of OPC or EC (0.29 vs. 1.08 episodes per patient-year; P<.0001) and fewer invasive fungal infections (15 vs. 28 episodes; P=.04, by chi2 test), but not with improved survival, compared with episodic fluconazole therapy. CONCLUSION: Continuous fluconazole therapy is not associated with significant risk of fluconazole-refractory OPC or EC, compared with episodic fluconazole therapy, in HIV-infected patients with access to active antiretroviral therapy.

AIDS-Related Opportunistic Infections↗
PubMed2005

Advances in diagnosing vaginitis: development of a new algorithm.

The current approach to diagnosing vulvovaginal symptoms is both flawed and inadequate. Mistakes occur at the level of the patient herself, her provider, and the sensitivity of office-based tests. Often, the differential diagnosis is so broad that providers may overlook some of the possibilities. A diagnostic algorithm which separates women into either a normal or elevated vaginal pH can successfully classify most women with vaginitis. Based on the amine test, vaginal leukocytes, and vaginal parabasal cells, those with an elevated pH can be placed into further diagnostic categories. Such an algorithm helps to prioritize different diagnoses and suggest appropriate ancillary tests.

Journal Article↗
PubMed2005

What's new in bacterial vaginosis and trichomoniasis?

The use of biochemical profiles and new molecular microbiologic methodologies is transforming our understanding of BV. Most important is the recognition of different subgroups of women who have BV who are at variable risk of certain obstetric and gynecologic complications. New diagnostic tests may soon be available that will allow women to test self-obtained specimens. Treatment of BV has lagged, although innovative methods appear to be helpful in managing recurrent diseases.

Anti-Infective Agents↗
PubMed2005

Emerging azole antifungals.

Systemic and superficial fungal infections have progressively emerged over the past few decades as an increasing cause of human disease, especially in the immunocompromised host. Control of fungal disease has proved difficult because few risk factors are potentially preventable; the population at highest risk for fungal disease, the immunocompromised patient, has been steadily increasing. There is a clear need for additional safe and effective therapeutic agents for the treatment of systemic fungal disease. A new generation of triazoles that includes voriconazole, posaconazole, ravuconazole and albaconazole has emerged and are presently in different phases of clinical investigation. These new triazoles have demonstrated a broad spectrum of activity, in particular against fungal pathogens previously resistant to previously available antifungals. This review highlights the emerging azole antifungals, both those available and in clinical development, and discusses their prospects for the future.

Animals↗
PubMed2004

Influence of sex hormones, HIV status, and concomitant sexually transmitted infection on cervicovaginal inflammation.

The impact of demographic characteristics, phase of the menstrual cycle, use of hormonal contraceptives, and concomitant lower genital-tract infections on cervicovaginal inflammatory cells was assessed in 967 women, 654 of whom were infected with human immunodeficiency virus type 1 (HIV-1). Cervicovaginal lavage (CVL) fluid was evaluated for total white blood cell (WBC), polymorphonuclear leukocyte, and monocyte counts. HIV-1 infection was not associated with statistically significant differences in numbers of inflammatory cells in CVL fluid except in 1 group--HIV-1-infected women with Chlamydia trachomatis infection had a 0.43 log(10) higher WBC count than their HIV-uninfected, chlamydia-positive counterparts (P=.04). Younger age and use of progesterone-based hormonal contraceptives were independently associated with increased numbers of inflammatory cells in CVL fluid. A 0.15-0.2 log(10) increase in inflammatory cells was seen in black versus white and Hispanic women after adjustment for known potential confounders. Progesterone-based contraceptives, younger age, and race have an independent effect on cervicovaginal inflammatory cells.

Adolescent↗
PubMed2004

Combination therapy for invasive mycoses: evaluation of past clinical trial designs.

BACKGROUND: Despite the availability of new antifungals, single-agent therapy frequently falls short of high cure rates. Combination therapy offers potentially higher cure rates, especially for resistant organisms. In vitro studies and experimental animal models have provided conflicting data. METHODS: Retrospective, randomized, controlled clinical studies were reviewed. RESULTS: Results indicate a clear advantage for polyene and flucytosine combination therapy in cryptococcal meningitis and a possible advantage for combination amphotericin B and fluconazole for candidemia. Unfortunately, the few studies published have been flawed by design problems that have compromised the determination of outcome. Study review allows investigators the opportunity to design future studies to ensure optimal evaluation of efficacy. CONCLUSION: Combination antifungal therapy is advantageous in cryptococcal diseases and may have a role in the treatment of invasive candidiasis. The greatest potential exists for combination therapy against aspergillosis and resistant fungi in patients with refractory mycotic disease who experience failure of monotherapy.

Antifungal Agents↗
PubMed2004

Maintenance fluconazole therapy for recurrent vulvovaginal candidiasis.

BACKGROUND: No safe and convenient regimen has proved to be effective for the management of recurrent vulvovaginal candidiasis. METHODS: After inducing clinical remission with open-label fluconazole given in three 150-mg doses at 72-hour intervals, we randomly assigned 387 women with recurrent vulvovaginal candidiasis to receive treatment with fluconazole (150 mg) or placebo weekly for six months, followed by six months of observation without therapy. The primary outcome measure was the proportion of women in clinical remission at the end of the first six-month period. Secondary efficacy measures were the clinical outcome at 12 months, vaginal mycologic status, and time to recurrence on the basis of Kaplan-Meier analysis. RESULTS: Weekly treatment with fluconazole was effective in preventing symptomatic vulvovaginal candidiasis. The proportions of women who remained disease-free at 6, 9, and 12 months in the fluconazole group were 90.8 percent, 73.2 percent, and 42.9 percent, as compared with 35.9 percent, 27.8 percent, and 21.9 percent, respectively, in the placebo group (P< 0.001). The median time to clinical recurrence in the fluconazole group was 10.2 months, as compared with 4.0 months in the placebo group (P<0.001). There was no evidence of fluconazole resistance in isolates of Candida albicans or of superinfection with C. glabrata. Fluconazole was discontinued in one patient because of headache. CONCLUSIONS: Long-term weekly treatment with fluconazole can reduce the rate of recurrence of symptomatic vulvovaginal candidiasis. However, a long-term cure remains difficult to achieve.

Administration, Oral↗
PubMed2004

Shuttle vectors for Candida albicans: control of plasmid copy number and elevated expression of cloned genes.

Plasmids containing the inosine monophosphate dehydrogenase gene CaIMH3 from Candida albicans strain ATCC 32354 transform their host to resistance against mycophenolic acid (MPA). The transformants maintain the plasmids at a high copy number (20-40 per cell) and express the CaIMH3 gene at very high levels relative to untransformed controls. The plasmid copy number can be controlled by the concentration of MPA in the media. The transformation procedure is reproducible and the efficiency of transformation is high, up to 15,000 per microgram. Unrearranged plasmids are readily recovered by transforming total DNA from transformants back into Escherichia coli. C. albicans genes cloned into the plasmid are expressed at elevated levels relative to untransformed controls. A derivative vector containing the CaMAL2 promoter and termination sequences expresses the CaERG11 ORF at high levels and confers moderate resistance to fluconazole. These shuttle vectors should facilitate global genomics approaches in C. albicans that have been hampered by its diploid genome.

Candida albicans↗
PubMed2004

Candida Vulvovaginitis in Pregnancy.

In the absence of epidemiologic studies over many decades, there are scant data on the prevalence and natural history of vaginal colonization and symptomatic Candida infections in pregnant women. The hormonal mileau of the vagina during pregnancy undoubtedly enhances Candida colonization and serves as a risk factor for symptomatic expression; however, the frequency, clinical manifestation, and response to therapy is largely based on empiric diagnosis of unsubstantiated disease. For reasons of liability, pregnant women have been largely excluded from controlled clinical treatment studies by the pharmaceutical industry; accordingly, treatment guidelines are dictated by opinions rather than data. As in nongravid women, management of symptomatic pregnant women should be based on confirmed diagnosis and not clinical impression.

Journal Article↗
PubMed2004

Risk factors for recurrent vulvovaginal candidiasis in women receiving maintenance antifungal therapy: results of a prospective cohort study.

OBJECTIVE: The purpose of this study was to examine risk factors for symptomatic vulvovaginal candidiasis episodes among women with recurrent vulvovaginal candidiasis (defined as >/=4 vulvovaginal candidiasis episodes in 1 year) who were receiving maintenance antifungal therapy. STUDY DESIGN: A prospective study of 65 women aged >/=18 years with recurrent vulvovaginal candidiasis who attended vaginitis clinics in Detroit, Mich, and Philadelphia, Pa. RESULTS: The 9-month risk of vulvovaginal candidiasis recurrence was 41.8%. Almost two fifths of the women reported activity limitations because of vulvovaginal candidiasis episodes, most or all of the time. Younger women and those women with a history of bacterial vaginosis were at increased risk of vulvovaginal candidiasis episodes. Behavioral factors that were associated significantly with increasing vulvovaginal candidiasis recurrence >/=2- fold included wearing pantyliners or pantyhose and consuming cranberry juice or acidophilus-containing products. CONCLUSION: The use of pantyliners or pantyhose, consumption of cranberry juice or acidophil-containing products, a history of bacterial vaginosis, and age <40 years were positively associated with a symptomatic vulvovaginal candidiasis episode.

Adult↗