Fluconazole resistant opportunistic oro-pharyngeal candida and non-candida yeast-like isolates from HIV infected patients attending ARV clinics in Lagos, Nigeria

Background

Oro-Pharyngeal Candidiasis (OPC) continues to be considered the most common opportunistic fungal disease in HIV/AIDS patients globally. Azole antifungal agent has become important in the treatment of mucosal candidiasis in HIV patients. Presently, antifungal drug resistance is fast becoming a major problem particularly with the immune depleted population.

Objectives

This study was designed to investigate the: existence of OPC, species distribution fluconazole susceptibility profile of yeast cells isolated from oral specimens of HIV/AIDS patients from Lagos Nigeria, between Oct. 2004 and June, 2005.

Methodology

The venous blood samples were screened for HIV antibodies using the Cappillus HIV I and II test kit (Trinity Biotech Plc UK), and Genie II HIV I and II EIA kit (Bio-Rad France). The positive results were subsequently confirmed at the laboratory attached to each of the clinics, using the Nigerian Federal Ministry of Health approved algorithm. The samples from 213 (108 females and 105 males) HIV positive patients were plated onto SD agar. The isolates were identified by morphotyping, microscopy and speciated using germ tube test and battery of biochemical sugar fermentation and assimilation tests. Fluconazole agar diffusion susceptibility testing was carried out on each isolates.

Results

Seventy-four (34.7%) isolates were recovered including one person with double isolates. Only 70(94.6%) of the isolates could be adequately speciated. Candida albicans 30 (40.5%) was the most frequently isolated species, the rest were non-albicans species, with the frequency of C. tropicalis › C. Krusei › C. glabrata and C. neoformans for species for species having up to 4 isolates. Four (30.8%) out of 13 isolates of C. tropicalis showed germ tube formation. While one C. albicans was germ-tube negative. Out of the 74 isolates tested for fluconazole sensitivity, 58(78.4%) were sensitive, MIC d″ 8µg/ml, 9(12.1%) were susceptible Dose Dependant (SDD), MIC 16–32 µg/ml and 7(9.5%) were resistant, MICs e″ 64µg/ml. Among the C. albicans isolates, 26(86.7%) were sensitive to fluconazole. The rank of susceptibility was C. albicans > C. tropicalis > C. Krusei for the most prevalent species.

Conclusion

We conclude that fluconazole resistant strains of oro-pharyngeal yeast-like cells exist in about 9.5% of HIV/AIDS patients with the above stated species distribution. We therefore, highlight the need for routine antifungal susceptibility testing on HIV patients with cases of initial or repeat episodes of OPC.     

浅议和法

从理、法、方、药的角度论述和法,指出该法在治疗上作用缓和,且注重调和气血及脏腑,旨在调盈济虚,平亢扶卑,从而使人体达到阴平阳秘的健康状态。     

三阴性乳腺癌的临床病理学特点及其预后影响因素

目的探讨三阴性乳腺癌(TNBC)的临床病理学特点及其预后的影响因素。方法收集经手术和病理证实的乳腺癌组织标本329例,免疫组织化学方法检测HER-2、ER、PR和p53表达,对照分析TNBC组和非三阴性乳腺癌(NTNBC)组的临床病理生物学特性,采用Kaplan-Meier法分析患者5年无瘤生存率。结果 NTNBC组占79.03%(260/329)。TNBC组占20.97%(69/329),中位年龄42岁,绝经前期73.91%(51/69),浸润性导管癌73.91%(51/69),阳性表达44.93%(31/69),p53T3(T5cm)27.54%(19/69),Ⅲ期30.43%(21/69),组织学Ⅲ级39.13%(27/69),淋巴结转移率55.07%(38/69),术后复发率27.54%(19/69),远处转移率18.84%(13/69),均高于NTNBC(P0.05)。TNBC和NTNBC5年无瘤生存率分别为75.36%(52/69)和86.92%(226/260),两组比较差异有统计学意义(P0.05)。结论 TNBC多发于绝经前女性,与NTNBC相比具有p53阳性表达率高、侵袭性强、局部复发高、淋巴结及远处转移率高的临床特点和病理生物学特性,预后较差。     

在婚男男性行为人群HIV感染及其双性性行为状况调查

目的 了解在婚男男性行为者(MSM)亚群特征、艾滋病感染状况、性行为和安全套使用情况.方法 在北京、哈尔滨、郑州和成都市采用“滚雪球”方法招募调查对象,通过匿名的方式进行问卷调查,包括社会人口学特征、同性和异性性伴种类、同性和异性性行为、安全套使用情况等,并进行HIV抗体检测.结果 4个市共有858名在婚MSM参加调查,平均年龄(38.3±9.1)岁,其中初中及以下文化程度占36.7％;自认为是同性、双性性取向和异性性取向/不确定者所占的比例分别为40.9％、54.3％和4.8％.感染HIV检出率为8.0％,其中成都市最高为13.3％.多因素分析显示,非本市户籍、同性性取向、居住在哈尔滨市、第一次发生插入性行为年龄＜18岁可能增加最近6个月与男性肛交时从不使用安全套的危险性(OR=1.5～2.1).年龄≥46岁、非本市户籍、居住在北京、异性性取向或性取向未确定、近6个月与男性肛交性行为从未使用安全套者可能增加与女性性交时从不使用安全套的危险性(OR=1.7～5.9).结论 在婚MSM亚群中HIV感染已处于高流行状态,该亚群存在的高比例无保护同性和异性性行为,加剧HIV在MSM和在婚女性人群间传播.     

Oral disease in the elderly in long-term hospital care

OBJECTIVE: To obtain baseline information on the prevalence of oral problems and disease in institutionalized elderly in a Scottish hospital.
DESIGN: A cross-sectional clinical investigation with complementary microbiological studies as appropriate. SUBJECTS AND METHODS: A cohort of 147 elderly in five long-term care wards; collection of demographic data; clinical examination to determine: i) the dental, and denture status and associated lesions such as Candida-associated denture stomatitis and angular cheilitis, ii) oral mucosal disease; swabs as appropriate for microbiology.
MAIN OUTCOME MEASURES: Dental status, root caries prevalence; denture status and hygiene, and associated disease; oral mucosal health.
RESULTS Median period of institutionalization of 147 patients was 15 months and 65% were aged 80 years or more; the majority were significantly mentally impaired; 52% wore complete dentures, 9% were partially dentate, 19% possessed partial or incomplete dentures; 20% were neither dentate nor had dentures. Of 80 patients who verbalired their complaints, 35% complained of dry mouth and 45% had denture-related problems, principally discomfort. The commonest oral finding was a coated tongue (56%); angular cheilitis was present in 25%, and Candida-associated denture stomatitis in 19%; none had oral ulcers.
CONCLUSIONS: There was considerable unmet dental need with significant oral disease and poor levels of oral and denture hygiene in this target group; both dental and medical professionals should act in concert to deliver curative as well as preventative dental care for the elderly living in institutions to improve their quality of life.     

Prolonged subcutaneous administration of recombinant alpha 2b interferon in patients with previously untreated Philadelphia chromosome-positive chronic-phase chronic myelogenous leukemia: effect on remission duration and survival: Cancer and Leukemia Group B study 8583 [see comments]

We investigated whether recombinant alpha 2b interferon (r alpha 2bIFN) would reduce the proportion of bone marrow Philadelphia chromosome (Ph) cells in chronic-phase chronic myelogenous leukemia (CML) by treating 107 previously untreated patients daily with r alpha 2bIFN at 5 x 10(6)IU/m2 subcutaneously. Patients with complete remission, partial remission, or partial hematologic remission received treatment until progression; those with progressive disease were taken off study and observed for survival. Sixty-three (59%) of the patients achieved at least a partial hematologic remission (24 complete remissions and 39 partial remissions). The median time to response for the 63 responders was 3.4 months, with a median duration of remission of 52 months and with 81% of responders continuing in remission beyond 12 months. The median survival for the 107 patients was 66 months. Of 78 patients with cytogenetic follow-up data, 31 (40%) achieved a partial cytogenetic response (n = 17) or a complete cytogenetic response (n = 14). The percentage of cytogenetic responders among all patients was 29% (31 of 107 patients). The median time to first cytogenetic response was 9 months. A major dose reduction of r alpha 2bIFN (> or = 50%) was required at some time during treatment in 38% of patients, 26% required 10% to 49% dose reductions, and 36% had minor dose reductions of < or = 10%. No association was observed between dose received and the attainment of a cytogenetic response. None of the usual prognostic factors (sex, race, performance status, weight loss, time from diagnosis to treatment, hepatosplenomegaly, age, symptoms, hemoglobin, or platelet, blast, basophil, or white blood cell count) were significantly related to survival. These data provide confirmation that major cytogenetic responses to prolonged administration of subcutaneous r alpha 2bIFN occur in 20% to 38% (95% confidence interval) of chronic- phase Ph-positive patients. Although it is hypothesized that patients achieving major cytogenetic responses to r alpha 2bIFN should have prolonged remission duration and survival compared with nonresponders, analyses of the effect of cytogenetic responders by both "landmark" and time-dependent covariate techniques fail to provide statistically significant evidence for an effect of cytogenetic response on remission duration or survival. This may be due in part to an effect size insufficiently large to be detected with the number of patients treated in this study. Thus, confirmation of remission duration or survival benefit, if any, of r alpha 2bIFN therapy in Ph-positive chronic-phase CML must await the outcome of randomized trials comparing IFN with conventional agents.     

Long-range mapping of the Philadelphia chromosome by pulsed-field gel electrophoresis

The Philadelphia chromosome (Ph1) of chronic myelogenous leukemia (CML) contains sequences from chromosome 9, including the ABL protooncogene, that have been translocated to the breakpoint cluster region (bcr) of chromosome 22, giving rise to a bcr-ABL fusion gene, whose product has been implicated in the genesis of CML. Although chromosome 22 translocation breakpoints in CML virtually always occur within the 5.8- kilobase (kb) bcr, chromosome 9 breakpoints have been identified within the known limits of ABL in only a few instances. For a better understanding of the variability of the breakpoints on chromosome 9, we studied the CML cell line BV173. Using pulsed-field gel electrophoresis (PFGE), large-scale maps of the t(9;22) junctions were constructed. The chromosome 9 breakpoint was shown to have occurred within an ABL intron, 160 kb upstream of the v-abl homologous sequences, but still 35 kb downstream of the 5'-most ABL exon. bcr-ABL and ABL-bcr fusion genes were demonstrated on the Ph1 and the 9q+ chromosomes, respectively; both of these genes are expressed. These results suggest that the 9;22 translocation breakpoints in CML consistently occur within the limits of the large ABL gene. RNA splicing, sometimes of very large regions, appears to compensate for the variability in breakpoint location. These studies show that PFGE is a powerful new tool for the analysis of chromosomal translocations in human malignancies.