Surgeon''s experience as a factor for emetic sequelae after middle ear surgery

OBJECTIVE: To evaluate the efficacy of melaleuca oral solution in AIDS patients with fluconazole-resistant oropharyngeal candida infections. DESIGN: A prospective, single center, open-labeled study. SETTING: A university-based inner-city HIV/AIDS clinic. PATIENTS: Thirteen patients with AIDS and oral candidiasis documented to be clinically refractory to fluconazole, as defined by failure to respond to a minimum of 14 days of > or = 400 mg fluconazole per day. Additionally, patients had in vitro resistance to fluconazole, defined by minimal inhibitory concentrations of > or = 20 microg/ml. INTERVENTIONS: Patients were given 15 ml melaleuca oral solution four times daily to swish and expel for 2-4 weeks. MAIN OUTCOME MEASURES: Resolution of clinical lesions of oral pseudomembranous candidiasis lesions. Evaluations were performed weekly for 4 weeks and at the end of therapy for clinical signs of oral candidiasis. Quantitative yeast cultures were performed at each evaluation. RESULTS: A total of 13 patients were entered into the study, 12 were evaluable. At the 2-week evaluation, seven out of 12 patients had improved, none were cured, and six were unchanged. At the 4-week evaluation, eight out of 12 patients showed a response (two cured, six improved), four were non-responders, and one had deteriorated. A mycological response was seen in seven out of 12 patients. A follow-up evaluation 2-4 weeks after therapy was discontinued revealed that there were no clinical relapses in the two patients who were cured. CONCLUSIONS: Melaleuca oral solution appears to be effective as an alternative regimen for AIDS patients with oropharyngeal candidiasis refractory to fluconazole.     

Potential utility of recombinant human GM-CSF as adjunctive treatment of refractory oropharyngeal candidiasis in AIDS patients

The aim of the study was to investigate the use of granulocyte macrophage-colony stimulating factor (GM-CSF) as an adjunctive treatment for clinically refractory mucosal candidiasis in patients with advanced AIDS. Three patients with advanced AIDS and oropharyngeal candidiasis clinically refractory to azoles or amphotericin B received GM-CSF for 14 days along with either fluconazole or amphotericin B. All three patients showed clinical improvement and mycological improvement without any adverse events. Thus, GM-CSF may be a possible alternative as adjunctive therapy in the management of refractory mucosal candidiasis in patients with advanced AIDS.     

Fluconazole. An update of its antimicrobial activity, pharmacokinetic properties, and therapeutic use in vaginal candidiasis

Fluconazole is a bis-triazole antifungal drug which has a pharmacokinetic profile characterised by its high water solubility, low affinity for plasma proteins, and metabolic stability. After a single 150 mg oral dose, therapeutic concentrations in vaginal secretions are rapidly achieved and are sustained for a duration sufficient to produce high clinical and mycological responses in nonimmunocompromised patients with vaginal candidiasis (candidosis). At this dosage, clinical and mycological responses have compared favourably with responses achieved after multiple dose regimens of other oral and intravaginal antifungal agents. Clinical efficacy rates have ranged between 92 and 99% at short term evaluation (5 days post-treatment). At 80 to 100 days post-treatment clinical efficacy rates of 91% have been reported. In addition, limited data indicate that fluconazole is more effective than placebo as prophylactic treatment of frequently recurring vaginal candidiasis. Single oral doses of fluconazole 150 mg are well tolerated. Most frequently observed adverse events are gastrointestinal symptoms, which are generally mild and transient in nature. Thus, fluconazole is a valuable alternative to established systemic and intravaginal azole antifungal drugs which are used to treat vaginal candidiasis. Moreover, in view of its favourable patient acceptability and compliance profile compared with alternative treatments, single-dose oral fluconazole should be considered as a first-line therapeutic choice for the treatment of women with vaginal candidiasis.     

IgE, IgA, and IgG responses to common yeasts in atopic patients

To assess the incidence of HIV infection and risk factors associated with HIV seroconversion among patients attending clinics for sexually transmitted diseases (STD), medical record reviews were conducted in 12 clinics in 7 U.S. cities. The records of all patients who initially tested negative for HIV from 1991 through 1996 and who received at least one additional HIV test during the study period were reviewed. In each of 7 cities, 5 to 112 patients seroconverted. Of the 286 seroconverters identified in total, 53% (152 of 286) were heterosexual men and 28% (81 of 286) were women. HIV incidence rates among men who have sex with men (MSM) ranged by city from 0.81 to 7.0 new infections/100 person-years. Rates among heterosexual men and women ranged from 0.018 to 1.2 infections/100 person-years. Multivariate analyses showed that drug use was associated with HIV seroconversion only among heterosexuals. Most new HIV infections in these clinics are being transmitted heterosexually and are associated with drug use. Nevertheless, MSM, particularly young MSM, are at greatest risk for HIV in this population: 1 of 47 seroconvert/year. The effective use of targeted prevention efforts depends upon the continued ability to monitor the incidence of HIV infection.     

Gynaecological conditions associated with HIV infection in women who are partners of HIV-positive Thai blood donors

Women who were partners of HIV-positive blood donors were enrolled in a study of heterosexual HIV transmission between March 1992 and December 1996 and were interviewed and examined. Gynaecological conditions, including cervical dysplasia, human papillomavirus (HPV) infection, gonorrhoea, chlamydial infection, trichomoniasis, bacterial vaginosis, vaginal candidiasis and syphilis were assessed in addition to HIV status and CD4 level. Of 481 women enrolled, 224 (46.6%) were HIV seropositive. HIV-infected women were more likely to have abnormal vaginal discharge on physical examination (OR=2.6, P <0.01), HPV infection with a high-risk type (OR=6.9, P <0.01), and cervical dysplasia (OR=5.3, P <0.01). The prevalence of other gynaecological conditions detected at the enrolment visit did not differ by HIV status. History of prior STD (OR=2.0, P <0.01) was more common among HIV-infected women. The median CD4 count was 400 cells/microl among HIV-infected women. The prevalence of abnormal vaginal discharge and bacterial vaginosis increased significantly with decreasing CD4 count. The prevalence of ectopy, vaginal candidiasis, and cervical dysplasia increased with decreasing CD4 count, but these trends were not significant. We conclude that HIV-infected Thai women appear to have increased prevalences of abnormal vaginal discharge, squamous intraepithelial lesions and self-reported history of STD.     

Increased cancer mortality following a history of nonmelanoma skin cancer

CONTEXT: Cancer registries have reported an increased incidence of melanoma and certain noncutaneous cancers following nonmelanoma skin cancer (NMSC). Whether these findings were attributable to intensified surveillance, shared risk factors, or increased cancer susceptibility remains unclear. OBJECTIVE: To determine whether a history of NMSC predicts cancer mortality. DESIGN: Prospective cohort with 12-year mortality follow-up adjusted for multiple risk factors. SETTING: Cancer Prevention Study II, United States and Puerto Rico. PARTICIPANTS: Nearly 1.1 million adult volunteers who completed a baseline questionnaire in 1982. MAIN OUTCOME MEASURE: Deaths due to all cancers and common cancers. RESULTS: After adjusting for age, race, education, smoking, obesity, alcohol use, and other conventional risk factors, a baseline history of NMSC was associated with increased total cancer mortality (men's relative risk [RR], 1.30; 95% confidence interval [CI], 1.23-1.36; women's RR, 1.26; 95% CI, 1.17-1.35). Exclusion of deaths due to melanoma reduced these RRs only slightly. Mortality was increased for the following cancers: melanoma (RR, 3.36 in men, 3.52 in women); pharynx (RR, 2.77 in men, 2.81 in women); lung (RR, 1.37 in men, 1.46 in women); non-Hodgkin lymphoma (RR, 1.32 in men, 1.50 in women); in men only, salivary glands (RR, 2.96), prostate (RR, 1.28), testis (RR, 12.7), urinary bladder (RR, 1.41), and leukemia (RR, 1.37); and in women only, breast (RR, 1.34). All-cause mortality was slightly increased (adjusted men's RR, 1.03 [95% CI, 1.00-1.06]; women's RR, 1.04 [95% CI, 1.00-1.09]). CONCLUSIONS: Persons with a history of NMSC are at increased risk of cancer mortality. Although the biological mechanisms are unknown, a history of NMSC should increase the clinician's alertness for certain noncutaneous cancers as well as melanoma.     

Efficacy of fluconazole in the treatment of upper gastrointestinal candidiasis in neutropenic patients with cancer: factors influencing the outcome

Fluconazole has proved to be effective in treating oropharyngeal and esophageal candidiasis in immunocompromised patients. However, sufficient data are lacking regarding the efficacy of this agent in neutropenic hosts. The aim of the present study was to determine the clinical and mycological efficacy of fluconazole and to define the factor(s) affecting the outcome of fluconazole therapy in severely neutropenic patients (peripheral neutrophil count, < 500/microL) with cancer who have oropharyngeal and/or esophageal candidiasis. One hundred eleven patients with 129 episodes of candidal infections were treated with intravenous and consequently oral fluconazole (200 mg/d and 100 mg/d, respectively). Overall clinical cure and mycological eradication rates were 82% and 56%, respectively. Persistent neutropenia (P < .01), infection with a non-albicans strain of Candida (P = .012), and administration of antifungal therapy during the second or a later neutropenic episode (P < .002) were independently associated with a worse outcome. We conclude that fluconazole is effective in the treatment of upper gastrointestinal candidiasis in neutropenic patients with cancer. Effective treatment of the underlying malignancy, with the resultant recovery from neutropenia, and the determination of the species of infecting Candida isolates are required for the prediction of the outcome of antifungal therapy.     

Risk factors for HIV infection in a rural cohort in Zimbabwe: a pilot study

OBJECTIVE: To identify demographic, sexual behavioural and cultural risk factors for human immunodeficiency virus (HIV) infection in a rural community in Zimbabwe. DESIGN: Prospective study. SETTING: Rural area in Zimbabwe. SUBJECTS: 207 subjects (81 males, 126 females) mean age 31.6 years (SD 15.3), range 12 to 76 years living in the area. MAIN OUTCOME MEASURES: HIV seropositivity and seroconversion, exposure or no exposure to risk factor. RESULTS: Prevalence of HIV was 7.7% and was associated with being divorced or widowed [Odds ratio (OR) 4.26, 95% confidence interval (CI) 1.17 to 14.97] and past history of sexually transmitted diseases (STDs) [(OR 3.54, 95% CI 1.31 to 9.89)]. Seroconversion rate was 3.6% per year and was associated with history of STD [Relative Risk (RR) 13.22, 95% CI 1.15 to 156.1)] during the follow up period. Individuals over 20 years of age, those reporting one or more sexual partners, those reporting irregular use of condoms and those scarified were at greater risk than their counterparts. Individuals who reported being circumcised were at slightly lesser risk than those who did not report circumcision. CONCLUSION: STDs were major determinants of HIV transmission in the study area. In addition being divorced or widowed was a risk factor for HIV infection. Scarification, tattooing and circumcision require further investigations.     

Fluconazole. An update of its pharmacodynamic and pharmacokinetic properties and therapeutic use in major superficial and systemic mycoses in immunocompromised patients

Fluconazole is a triazole antifungal agent which is now an established part of therapy in patients with immune deficiencies. It is effective against oropharyngeal/oesophageal candidiasis (candidosis) when used orally once daily either as treatment or secondary prophylaxis in patients with AIDS or as treatment or primary prophylaxis in neutropenia associated with cancer therapy. Fluconazole also resolves symptoms in up to 60% of patients with cryptococcal meningitis and AIDS. However, in this infection its efficacy as treatment relative to that of amphotericin B is equivocal, and its major role is as the drug of choice for maintenance therapy following amphotericin B induction. In this regard, fluconazole has been proven superior to amphotericin B and to itraconazole 200 mg/day. Comparisons with other drugs used for the treatment of mucosal candidiasis in patients with AIDS show fluconazole to be superior to nystatin, similar to itraconazole and at least as effective as clotrimazole and ketoconazole; it was more so than the latter azole in 1 study. In patients undergoing chemotherapy or bone marrow transplantation, fluconazole as primary prophylaxis has produced greater clinical benefit than a clotrimazole regimen. The incidence of adverse events appears to be somewhat higher in patients with AIDS compared with HIV-negative cohorts, but the qualitative pattern of events is similar. The most frequent events are gastrointestinal complaints, headache and skin rash: rare exfoliative skin reactions and isolated instances of clinically overt hepatic dysfunction have occurred in patients with AIDS. Issues yet to be clarified include: the use of fluconazole in children with AIDS, in whom results have been promising; its efficacy against other fungal infections encountered in immunocompromised patients; whether the drug influences mortality, as has been suggested by one placebo-controlled trial in patients undergoing bone marrow transplant; and the appropriateness of its potential for use as primary prophylaxis against cryptococcal meningitis in patients with AIDS, where it shows efficacy but there is concern over increasing risk of development of secondary resistance. Notwithstanding these undefined aspects of its clinical profile, fluconazole is now confirmed as an important antifungal drug in the management of fungal infections in patients with immune deficiencies. In patients with AIDS it is the present drug of choice as maintenance therapy against cryptococcal meningitis and is a preferred agent for secondary prophylaxis against candidal infections; it is also a favoured agent for primary prophylaxis in patients at risk because of neutropenia associated with chemotherapy or bone marrow transplantation .     

Prevalence, incidence, and risks for HIV-1 infection in female sex workers in Miami, Florida

Annual cross-sectional prevalence, incidence of new infection, and risks for human immunodeficiency virus type 1 (HIV-1) infection were studied in 607 women convicted of prostitution between October 1987 and December 1990 and tested for HIV under court order. Cross-sectional prevalence was stable for 4 years (23-24% positivity in 1987-1991, p = 0.6). However, the incidence of new infections (rate of seroconversion) in 264 women tested more than once increased significantly each year from 12 per 100 person-years in 1987-1988 to 19 per 100 person-years in 1991 (p < 0.03). Seroconverters were more likely to be young black women with a prior history of syphilis or gonorrhea. A new episode of syphilis or rectal gonorrhea during the follow-up period predicted HIV seroconversion in a survival analysis model. Female sex workers are at great risk of acquiring HIV infection. Although HIV prevalence in cross-sectional samples was stable, incidence was increasing. Interpretation of prevalence trends from convenience samples, such as screening programs, may be difficult because changes in incidence may not be detected.     

HIV infection in non-pregnant women: a review of current knowledge

HIV infection has become an important health problem among American women. The natural history of HIV infection and AIDS appears to be similar for women and men, and preliminary studies demonstrate similar survival and clinical events for both sexes. The natural history and presentation of common gynecologic infections and conditions may be altered by HIV. Most is known about cervical dysplasia. The risk of cervical dysplasia appears to be increased in women with HIV infection, progression of cervical dysplasia may be more rapid, severity of disease increased, particularly for women with HIV-related immunocompromise. Recently, the Centers for Disease Control and Prevention added invasive cervical cancer as an AIDS-defining condition. Vulvovaginal candidiasis, sexually transmitted diseases, including syphilis, herpes, and cytomegalovirus, and pelvic inflammatory disease are also common in HIV-infected women. Preliminary data suggest that these conditions may be more severe and more difficult to treat in HIV-infected women than uninfected women. Women who are HIV-infected should have thorough evaluation and follow up of all gynecologic conditions, particularly as they become immunosuppressed.     

Comparison of itraconazole and ketoconazole in HIV-positive patients with oropharyngeal or esophageal candidiasis. Human Immunodeficiency Virus Itraconazole Ketoconazole Project Group

The efficacy of oral itraconazole and ketoconazole in the treatment of oropharyngeal and/or esophageal candidiasis, and the rate of post-treatment relapse, were compared in a multicenter, prospective, double-blind, double-dummy, randomized, parallel-group trial. A total of 143 adult HIV-positive patients with oropharyngeal and/or esophageal candidiasis were assigned to receive either itraconazole or ketoconazole (200 mg/day). Patients with oropharyngeal and esophageal candidiasis were treated for 2 and 4 weeks, respectively. Patients were evaluated clinically and mycologically after 1, 2 and 4 (for esophageal patients) weeks of therapy, and relapses were compared in a 6-week post-treatment follow-up period. Of 129 evaluable patients, 98 had oropharyngeal candidiasis and 31 esophageal infection. CDC classification, CD4+ cell counts, and number of previous episodes of oropharyngeal or esophageal candidiasis were comparable in both groups. Oropharyngeal infection was cleared clinically at 21 days in 71% of patients receiving itraconazole and 60% receiving ketoconazole, and esophageal candidiasis was cleared at 41 days in 100% of patients receiving itraconazole and 91% receiving ketoconazole. Marginally significant differences were found between itraconazole and ketoconazole in rates of clearing of infection clinically in patients with oropharyngeal and esophageal candidiasis (p = 0.0614 and 0.0781, respectively). Mean rates of infection relapse were not statistically different in the two treatment groups. Adverse events were generally mild and not considered drug related. Itraconazole is marginally more efficacious than ketoconazole in the treatment of oropharyngeal and esophageal candidiasis in HIV-positive patients and both drugs appear safe and well tolerated.     

Oropharyngeal candidiasis in patients with AIDS: randomized comparison of fluconazole versus nystatin oral suspensions

A total of 167 human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis were randomly assigned to receive 14 days of therapy with liquid suspension fluconazole (100 mg once daily) or liquid nystatin (500,000 U four times daily). At day 14, 87% of the fluconazole-treated patients were clinically cured, as opposed to 52% in the nystatin-treated group (P < .001). Fluconazole eradicated Candida organisms from the oral flora in 60%, vs. a 6% eradication rate with nystatin (P < .001). The fluconazole group had fewer relapses noted on day 28 (18%, vs. 44% in the nystatin group; P < .001). This relapse difference no longer existed by day 42. Fluconazole oral suspension as a systemic therapy was more effective than liquid nystatin as a topical therapy in the treatment of oral candidiasis in HIV-infected patients and provided a longer disease-free interval before relapse.     

Invasive pneumococcal disease in a cohort of predominantly HIV-1 infected female sex-workers in Nairobi, Kenya

BACKGROUND: HIV infection is a major risk factor for pneumococcal disease in industrialised countries. Although both are common infections in sub-Saharan Africa, few studies have investigated the importance of this interaction. We have followed up a cohort of female sex-workers in Nairobi and report here on the extent of invasive pneumococcal disease. METHODS: A well-established cohort of low-class female sex-workers, based around a community clinic, was followed up from October, 1989, to September, 1992. 587 participants were HIV positive and 132 remained HIV negative. Set protocols were used to investigate common presentations. Cases were identified clinically and radiographically. Streptococcus pneumoniae and other pathogens were diagnosed by culture. FINDINGS: Seventy-nine episodes of invasive pneumococcal disease were seen in the 587 HIV-positive women compared with one episode in the 132 seronegative women (relative risk 17.8, 95% CI 2.5 to 126.5). In seropositive women the incidence rate was 42.5 per 1000 person-years and the recurrence rate was 264 per 1000 person-years. By serotyping, most recurrent events were re-infection. A wide spectrum of HIV-related pneumococcal disease was seen: only 56% of cases were pneumonia; sinusitis was seen in 30% of cases, and occult bacteraemia, a novel adult presentation, in 11%. Despite forty-two bacteraemic episodes, no deaths were attributable to Strep pneumoniae. At first presentation the mean CD4 cell count was 302/microL(SD 191) and was 171/microL (105) for recurrent episodes. During acute Strep pneumoniae infection the CD4 cell count was reversibly suppressed (mean fall in sixteen episodes, 105/microL [123]). The neutrophil response to acute infection was blunted and was correlated with CD4 count (r=0.50, 95% CI 0.29 to 0.66). Strep pneumoniae caused more disease, at an earlier stage of HIV immunosuppression, than Mycobacterium tuberculosis or non-typhi salmonellae. INTERPRETATION: Our study highlights the importance of the pneumococcus as an early but readily treatable complication of HIV infection in sub-Saharan Africa.     

Refractory mucosal candidiasis in patients with human immunodeficiency virus infection

Difficult-to-manage mucosal candidal infection has been a hallmark of individuals with advanced infection due to human immunodeficiency virus type 1. In this AIDS Commentary, Drs. Fichtenbaum and Powderly comprehensively review the literature and their experience with refractory candidiasis in such patients. Of interest is their delineation of resistance, a lack of susceptibility to an antifungal agent in vitro among patients with refractory or clinically unresponsive disease. These authors believe that the establishment of resistance should be based upon standards established by the National Committee on Clinical Laboratory Standards, which they propose to define as a failure to respond to systematic therapy with specific doses of itraconazole, fluconazole, or parenterally or orally administered amphotericin B within 14 days. There have been many definitions of "refractory candidiasis," and the one proposed by these authors will be debated; however, this definition has the advantage of establishing a standard by which to judge the efficacy of their proposed algorithm for the treatment of persistent or refractory oropharyngeal candidal infections. Drs. Fichtenbaum and Powderly have performed a useful service in their attempt to bring coherence to the management of this common and often vexing problem.     

Disability, the risk of disability and changes in work capacity-- unacceptable conditions for insurance in occupational injuries and diseases

OBJECTIVE: To identify factors associated with failure to return for HIV post-test counselling in pregnant women in Kigali (Rwanda). SUBJECTS AND METHODS: In the context of a study on the impact of HIV infection on pregnancy, HIV-1-antibody testing was offered to all pregnant women attending the antenatal clinic of the Centre Hospitalier de Kigali from July 1992 to August 1993. Pre-test counselling was performed after verbal informed consent was obtained. Two weeks later, we formally enrolled all HIV-positive women and a corresponding number of HIV-negative women in a cohort. At this visit, post-test counselling was given to those wishing to be informed of their HIV serostatus. Level of knowledge about modes of HIV transmission and condom use were recorded. Four months after delivery, another interview was conducted to determine the proportion of women who used condoms regularly. RESULTS: A total of 1233 pregnant women were screened. The HIV seroprevalence was 34.4% [95% confidence interval (CI), 31.7-37.1]; 271 (63.9%) out of 424 HIV-positive and 577 (71.3%) out of 809 HIV-negative women asked for their HIV serostatus (P = 0.008). In multivariate analysis, the only variable significantly associated with failure to return for post-test counselling was a positive HIV test result (odds ratio, 0.7; 95% CI, 0.5-0.9; P = 0.009), independently of obstetrical history and socioeconomic characteristics. Among the 848 women who had post-test counselling, 50.9% of the HIV-positive women and 94.6% of the HIV-negative women stated that they planned to inform their partner of their serostatus (P = 0.0001). More than 95% of the women interviewed knew about sexual and parenteral transmission of HIV, but half were unaware of mother-to-child transmission. More than 80% of the women had seen a condom before, but 14% only had used it at least once. Among women who were sexually active 4 months after delivery, 8.8% of the HIV-positive and 3.9% of the HIV-negative women reported using a condom (P = 0.04). CONCLUSION: Innovative approaches for HIV testing and counselling programs are needed and the importance of psychosocial and cultural factors associated with HIV testing should be emphasized in African populations.     

The association between cigarette smoking and selected HIV-related medical conditions

OBJECTIVE: To clarify the effect of cigarette smoking on the development of conditions associated with HIV infection. DESIGN: Prospective and retrospective cohort study, with interview and examination twice a year since 1988. METHODS: Data on 516 HIV-infected men from cohorts of homosexual and bisexual men in San Francisco, Denver and Chicago, who were repeatedly interviewed and examined between 1988 and 1992, were analysed. After excluding men who did not have well-defined dates of seroconversion and those who were classified as ex- or intermittent smokers, 232 men remained for analysis: 106 were smokers and 126 were non-smokers. Univariate and Kaplan-Meier survival analyses were performed to assess the relationship between cigarette smoking and loss of CD4+ T-lymphocytes, diagnosis of any AIDS-defining illness, and specific diagnosis of Kaposi's sarcoma, Pneumocystis carinii pneumonia (PCP), oral candidiasis, hairy leukoplakia, and community-acquired pneumonia. RESULTS: By univariate analyses, cigarette smoking was not associated with clinical AIDS, loss of CD4+ cells, Kaposi's sarcoma or PCP, but was significantly associated with oral candidiasis [relative risk (RR), 1.32; 95% confidence interval (CI), 1.02-1.70], hairy leukoplakia (RR, 1.51; 95% CI, 1.15-1.99), and community-acquired pneumonia (RR, 2.62; 95% CI, 1.30-5.27). Dose-response effect was also evident for these three conditions (all P < 0.01). Kaplan-Meier survival analysis indicated no association between cigarette smoking and time of progression to clinical AIDS, Kaposi's sarcoma (KS), or PCP (P = 0.62, 0.54 and 0.11, respectively) but showed that cigarette smokers developed oral candidiasis, hairy leukoplakia, and pneumonia more quickly than non-smokers (P = 0.031, 0.006 and 0.009, respectively). CONCLUSIONS: Cigarette smoking was not associated with an increased likelihood or rate of developing KS, PCP or AIDS, but was associated with developing community-acquired pneumonia, oral candidiasis, and hairy leukoplakia in these HIV-infected men.     

Fluconazole versus Candida albicans: a complex relationship

A murine model of systemic candidiasis was used to assess the virulence of serial Candida albicans strains for which fluconazole MICs were increasing. Serial isolates from five patients with 17 episodes of oropharyngeal candidiasis were evaluated. The MICs for these isolates exhibited at least an eightfold progressive increase from susceptible (MIC < 8 microg/ml; range, 0.25 to 4 microg/ml) to resistant (MIC >/= 16 microg/ml; range, 16 to >/=128 microg/ml). Virulence of the serial isolates from three of five patients showed a more than fivefold progressive decrease in the dose accounting for 50% mortality and was associated with development of fluconazole resistance. Low doses of fluconazole prolonged survival of mice infected with susceptible yeasts but failed to prolong survival following challenge with a resistant strain. In addition, a decreased burden of renal infection was noted in mice challenged with two of the three resistant strains. This was consistent with reduced virulence. Fluconazole did not further decrease the level of infection. In the isolates with a decrease in virulence, two exhibited overexpression of CDR, which encodes an ABC drug efflux pump. In contrast, serial isolates from the remaining two patients with the development of resistance did not demonstrate a change in virulence and fluconazole remained effective in prolonging survival, although significantly higher doses of fluconazole were required for efficacy. Resistant isolates from both of these patients exhibited overexpression of MDR. This study demonstrates that decreased virulence of serial C. albicans isolates is associated with increasing fluconazole MICs in some cases but not in others and shows that these low-virulence strains may not consistently cause infection.     

The role of hormone replacement therapy in the risk for breast cancer and total mortality in women with a family history of breast cancer

BACKGROUND: The risks and benefits of hormone replacement therapy (HRT) are of considerable interest and importance, especially in terms of whether they differ among subsets of women. OBJECTIVE: To determine whether HRT is associated with increased risks for breast cancer and total mortality in women with a family history of breast cancer. DESIGN: Prospective cohort study. SETTING: Population-based sample of midwestern post-menopausal women enrolled in an observational study of risk factors for cancer. PARTICIPANTS: Random sample of 41,837 female Iowa residents 55 to 69 years of age. MEASUREMENTS: Incidence rates of and relative risks for breast cancer (n = 1085) and total mortality (n = 2035) through 8 years of follow-up were calculated by using data from the State Health Registry of Iowa and the National Death Index. RESULTS: A family history of breast cancer was reported by 12.2% of the cohort at risk. Among women with a family history of breast cancer, those who currently used HRT and had done so for at least 5 years developed breast cancer at an age-adjusted annual rate of 61 cases per 10,000 person-years (95% CI, 28 to 94 cases); this rate was not statistically significantly higher than the rate in women who had never used HRT (46 cases per 10,000 person-years [CI, 36 to 55 cases]). Among women with a family history, those who used HRT had a significantly lower risk for total mortality than did women who had never used HRT (relative risk, 0.67 [CI, 0.51 to 0.89]), including total cancer-related mortality (relative risk, 0.75 [CI, 0.50 to 1.12]). The age-adjusted annual mortality rate for women using HRT for at least 5 years was 46 deaths per 10,000 person-years (CI, 19 to 74 deaths); this is roughly half the rate seen in women who had never used HRT (80 deaths per 10,000 person-years [CI, 69 to 92 deaths]). CONCLUSIONS: These data suggest that HRT use in women with a family history of breast cancer is not associated with a significantly increased incidence of breast cancer but is associated with a significantly reduced total mortality rate.     

Matrix metalloproteases and their inhibitors in the pleura

Vulvovaginal candidiasis is a frequent inflammatory process in women but it has not been widely studied in female sex workers (FSWs). To estimate the frequency of Candida species infection in FSWs and to identify related risk factors and clinical findings, we carried out a retrospective study of 1923 FSWs over 11 years. We also performed a prospective study of 163 consecutive FSWs with a history of candidiasis during a 4-year period. Candida species were isolated in 1967 samples (18.5% of the total). Candida albicans (89.3%) was the most frequent species, followed by Candida glabrata (2.7%), Candida parapsilosis (1.2%) and Saccharomyces cerevisiae (0.4%). In the prospective study of 163 patients, we found vaginal discharge in 76.1% of cases, soreness in 52.1% and vulval pruritus in 32.5%. We identified 12 patients (7.4%) with recurrent vulvovaginal candidiasis. No statistical difference was found between recurrent vulvovaginitis and the use of oral contraceptives, oral sex, tight-fitting clothing and synthetic underwear. FSWs have the same prevalence of candidiasis as other groups of women described in published literature. The proportion of albicans and non-albicans species does not differ between women with recurrent and non-recurrent vulvovaginal candidiasis (VVC).