Experience with amphotericin-B in the treatment of systemic candidiasis in burn patients

Systemic candidiasis has emerged as a major cause of death in burn patients. An increase both in the incidence of systemic candidiasis and its increase as a cause of death has been observed. Treatment with systemic amphotericin-B prior to 1971 at our institution was rarely successful. This was felt to be in part due to lack of sufficiently early recognition of the infection and to delay in the initiation of appropriate systemic therapy. From 1971 to 1975, fifteen patients have been treated with systemic amphotericin-B with one death. There have been no fatalities from candidiasis since 1972. No serious complications attributed to the use of amphotericin-B were observed. Prompt initiation of therapy with intravenous amphotericin-B is advised for burn patients in whom systemic candidiasis is present.     

Genetic susceptibility to systemic lupus erythematosus in the genomic era

Our understanding of the genetic basis of systemic lupus erythematosus (SLE) has been rapidly advanced using large-scale, case-control, candidate gene studies as well as genome-wide association studies during the past 3 years. These techniques have identified more than 30 robust genetic associations with SLE including genetic variants of HLA and Fcγ receptor genes, IRF5, STAT4, PTPN22, TNFAIP3, BLK, BANK1, TNFSF4 and ITGAM. Most SLE-associated gene products participate in key pathogenic pathways, including Toll-like receptor and type I interferon signaling pathways, immune regulation pathways and those that control the clearance of immune complexes. Disease-associated loci that have not yet been demonstrated to have important functions in the immune system might provide new clues to the underlying molecular mechanisms that contribute to the pathogenesis or progression of SLE. Of note, genetic risk factors that are shared between SLE and other immune-related diseases highlight common pathways in the pathophysiology of these diseases, and might provide innovative molecular targets for therapeutic interventions.     

Ketoconazole in the treatment of vaginal candidiasis

In a preliminary open prospective study ketoconazole (Nizoral; Janssen) 200 mg twice daily for 5 consecutive days was found to be extremely effective in treating vulvovaginal candidiasis, producing cure rates of 96% at 7 days and 92% at 28 days. The oral route of administration has definite advantages over the vaginal route and improves patient compliance. No side-effects related to treatment were found in this study.     

Emergence of resistance to amikacin during treatment of burn wounds: the role of antimicrobial susceptibility testing.

Amikacin has been used to treat Providencia stuarii infections on the Burn Service at Los Angeles County/University of Southern California Medical Center since March, 1973. The median minimal inhibitory concentration (MIC) of strains collected on this service prior to the introduction of amikacin was 3.13 mug. per milliliter, whereas the median MIC of strains collected during the last 4 months of the study was 12.5 mug per milliliter. High bactericidal concentrations (MBC) noted at the time of initial studies predicted the emergence of resistant clones, with MBV values rising to as great as 100 mu per milliliter. Further, isolates from burn patients during the initial 5 days of treatment with amikacin had a median MIC of 6925 mug per milliliter, in contrast to values of 25 mug per milliliter in strains isolated after 5 days of treatment. The epidemiologic significance of intensive treatment of gram-negative infections occurring in a close population with selected antibiotics is discussed. The performance of susceptibility tests which included determination of bactericidal concentrations was a major tool in the recognition of the potential for selection of resistant micro-organisms.     

肿瘤干细胞、耐药及治疗新趋势

手术、化疗及放疗等恶性肿瘤的治疗已取得一定效果,但仍有部分肿瘤复发、转移.近年研究发现,肿瘤干细胞多处于细胞G0期,具有很高的端粒酶活性及DNA复制修复能力,通过高表达三磷酸腺苷结合盒转运蛋白(ABC 转运蛋白)和抗凋亡基因而逃避化疗及放疗,最终导致肿瘤复发和转移.消灭肿瘤干细胞已成为目前研究热点,主要有诱导肿瘤干细胞进入细胞增殖周期、使用ABC转运蛋白抑制剂、抑制肿瘤干细胞端粒酶活性、细胞特异性标志靶向治疗、免疫诱导等,并取得了一定疗效.     

2010～2012年我院深部抗真菌药使用情况分析

目的对我院深部抗真菌药物的使用情况进行统计与评价,为临床合理用药和有效管理提供参考。方法使用限定日剂量（DDD）作为分析单位,计算累积DDDs,并以此为基础对2010～2012年我院（二级甲等）住院患者的深部抗真菌药物用药数量与金额、日均费用（DDC）、药物利用指数（DUI）、药物使用强度（AUD）进行统计计算。结果我院深部抗真菌药品种、使用数量和销售金额均呈逐年上升趋势。氟康唑是治疗深部真菌感染的主要药品。深部抗真菌药的用药强度逐年增长趋势明显。结论为促进抗菌药物合理应用,需进一步分析原因,加强监控。     

Itraconazole in the treatment of acute vaginal candidiasis

In a multicentre open prospective study itraconazole was evaluated in the treatment of acute vaginal candidiasis. Two dosage regimens were tested--200 mg twice a day for 1 day and 200 mg twice a day for 2 days. There were no statistically significant differences between these dosages, and cure rates at 7 and 28 days after treatment were 83% and 75% respectively. These are marginally lower than those produced by longer courses of oral ketoconazole (Nizoral; Janssen) and vaginal econazole nitrate but the advantages are better patient compliance and greater cost-effectiveness.     

Betablockers compared with antithyroid drugs as preoperative treatment in hyperthyroidism: drug tolerance, complications, and postoperative thyroid function

Subtotal thyroid resection or hemithyroidectomy was performed for hyperthyroidism on two groups of patients: 84 treated before surgery with antithyroid drugs and thyroxin and 111 given only beta-blocking agents before surgery. These two patient groups were compared with reference to preoperative medication, operation, immediate postoperative course, and late results, with follow-up for 3 to 7 years. The advantages of beta-blockers compared with conventional antithyroid medication were lack of adverse reactions, rapid effect of treatment, considerably shortened preoperative treatment time, and fewer outpatient visits, with consequent financial benefit. No disadvantages of beta-blockers were found except that 18% of the patients required additional propranolol in the immediate postoperative period. There were no surgical complications in either group other than a mild persistent hypocalcemia in two patients from the beta-blocked group. The serum thyrotropin levels during the first 6 postoperative months were significantly higher in the patients treated with antithyroid drugs. The frequency of postoperative thyroid dysfunction showed no intergroup difference during the observation period. Signs of hypofunction, necessitating thyroxin supplementation, were observed in 28.6% of patients in the antithyroid drug/thyroxin group and in 25.7% in the beta-blocker group. Toxic recurrence occurred in 1.8% of the group that received beta-blockers and in 1.2% of the other patients. The study demonstrated that beta-adrenoceptor blockade is a safe method for preoperative treatment in hyperthyroidism, with advantages for patients and regarding costs.     

Advances in the treatment of systemic lupus erythematosus: From back to the future,to the future and beyond

There have been many advances in the diagnosis and therapeutic management of systemic lupus erythematosus (SLE) over the past decades. Following more than eleven centuries of therapeutic uncertainty, the discovery of the therapeutic properties of glucocorticoids is without any doubt one of the most significant advance in the field of autoimmune diseases. The many progresses made by rapidly growing chemical industry of the 19th century chemistry have allowed the identification of valuable therapeutic compounds such as anti-malarials, cyclophosphamide, azathioprine, cyclosporine and later mycophenolate mofetil, which have all profoundly changed the face of the disease. A very visible consequence of this is the profound improvement in the prognosis of the disease, with 10-year survival rates of more than 90% in most dedicated centres. Following the development of biotherapies in rheumatoid arthritis, the late 20th century has slowly opened a new era for the treatment of SLE, that of targeted therapies. With the approval of belimumab in 2011 and 74 targeted therapies in clinical development, we may expect great changes in the therapeutic management of SLE. Those molecules target inflammatory cytokines or chemokines and their receptors, B cells or plasma cells, intracellular signalling pathways, B/T cells co-stimulation molecules, interferons, plasmacytoid dendritic cells, as well as various other targets of interest. Current challenges are now slowly shifting from whether some new drugs will be available to how to select the most adequate drug (or drug combination) at the patient-level.     

Value of the Candida antigen assay in diagnosis of systemic candidiasis in burn patients.

The Cand-tec latex agglutination test was used to analyze 2,575 serum samples from 47 consecutive burn patients at risk for systemic candidiasis and serum samples from 24 nonhospitalized control subjects. One burn patient had systemic candidiasis documented by culture of a deep biopsy specimen. In addition, blood culture produced positive results in one patient with no other evidence of systemic candidiasis. Wound, sputum, mucous membrane, or gastrointestinal tract specimens were cultured in 25 of 47 (53%) patients with no evidence of systemic candidiasis. Surveillance cultures were negative in 19 (40%) patients and there were no signs of systemic candidial infection. The sensitivity of the Candida antigen titer was 100% at titers of greater than or equal to 1:2, greater than or equal to 1:4, greater than or equal to 1:8, and greater than or equal to 1:16. Specificity was 77% at titers of greater than or equal to 1:4, 94% at titers of greater than or equal to 1:8, and 100% at titers of greater than or equal to 1:16. The positive predictive value ranged from 6.0% at greater than or equal to 1:4 to 100% at greater than or equal to 1:16. The negative predictive value was 100% for all titer values. The Cand-tec antigen test shows poor specificity and poor positive predictive value for the detection of systemic candidiasis in burn patients.     

Photodynamic therapy for the treatment of buccal candidiasis in rats

The study objective was to evaluate the effects of photodynamic therapy on buccal candidiasis in rats. After experimental candidiasis had been induced on the tongue dorsum, 72 rats were distributed into four groups according to treatment: treated with laser and methylene blue photosensitizer (L+P+); treated only with laser (L+P−); treated only with photosensitizer (L−-P+); not treated with laser or photosensitizer (L−P−). The rats were killed immediately, 1 day, or 5 days after treatment, for microscopic analysis of the tongue dorsum. Observation verified that the photodynamic therapy group (L+P+) exhibited fewer epithelial alterations and a lower chronic inflammatory response than the L−P− group. The group L+P− presented more intense epithelial alterations and chronic inflammatory response than the remaining groups. The L−P+ group showed tissue lesions similar to those of the L−P− group. In conclusion, rats treated with photodynamic therapy developed more discrete candidiasis lesions than did the remaining groups.