In vitro activity of caspofungin compared to amphotericin B, fluconazole, and itraconazole against Candida strains isolated in a Turkish University Hospital.

We investigated the in vitro activity of caspofungin compared to amphotericin B, fluconazole, and itraconazole against clinical strains of Candida spp. (n =239). Antifungal susceptibility tests were done in accordance with NCCLS M27-A2 microdilution method and the results were read after 24 and 48 h. In general, 24 h MIC readings were similar to those at 48 h for most isolates and all antifungal agents. Caspofungin was active against all species tested. Caspofungin MICs of Candida parapsilosis were slightly higher than those for other Candida spp. Caspofungin MIC (microg/ml) ranges at 24 h for C. albicans, C. glabrata, C tropicalis, C. parapsilosis, C kefyr, C krusei, C. lusitaniae, C. norvegensis, C. guilliermondii and C. lipolytica were 0.06-2, 0.125-2, 0.125-2, 1-4, 0.125-2, 1-2, 0.5-2, 0.5-1, 0.5-2 and 1-2, respectively. Eagle (paradoxical) effect was observed in 31 and 8% of the isolates at highest concentrations of caspofungin and itraconazole, respectively. The activity of caspofungin against fluconazole- and/or itraconazole-resistant isolates was similar to that detected for the susceptible ones. We conclude that caspofungin appears as a promising antifungal agent with enhanced activity against Candida, including the azole-resistant strains.     

The correlation of plasma homocysteine with insulin resistance in polycystic ovary syndrome

AIM: This study aims to investigate the existence of any relationship between homocysteine levels and insulin resistance in Turkish women with polycystic ovary syndrome. METHODS: A case-controlled, cross-sectional, observational study was undertaken in a total of 94 infertile Turkish women who required professional help in the Department of Infertility of Dr Zekai Tahir Burak Women's Health Research and Education Hospital. The correlation between serum homocysteine with age, body mass index, hormone profile, fasting insulin and glucose concentrations and insulin resistance were examined in patients with polycystic ovary syndrome and the results were compared to those of women with normal ovaries, who served as a control group. RESULTS: The mean serum fasting glucose and insulin levels, thus insulin resistance index of women with polycystic ovary syndrome, were significantly higher than those of the control subjects. The mean serum homocysteine levels were significantly higher in women with polycystic ovary syndrome than those in the control group. A positive correlation was detected between the mean homocysteine, the insulin resistance index determined by homeostasis model assessment and the fasting insulin levels in polycystic ovary syndrome patients. CONCLUSIONS: Serum homocysteine levels are elevated in women with polycystic ovary syndrome, and this elevation is associated with the serum insulin level rather than androgen excess. The intense treatment of hyperhomocysteinemia in women with polycystic ovary syndrome might improve reproductive outcome and contribute to protection from cardiovascular risks.     

Ravuconazole Eisai/Bristol-Myers Squibb

Eisai and Bristol-Myers Squibb (BMS) are developing the triazole, ravuconazole, as a potential treatment for fungal infection [187888]. Eisai selected the compound for further development on the basis of its good safety profile and well-balanced antifungal activity [187888]. Ravuconazole has a broader antifungal spectrum than fluconazole and itraconazole, particularly against strains of Candida krusei and Cryptococcus neoformans [271854], [342757], [370312]. By June 1999, the compound was undergoing phase II trials [327113]. In November 2001, it was reported that BMS was seeking a co-development partner for the compound [430011]. In October 2001, analysts at ABN Amro predicted sales of US $50 million in 2003 [444020].     

Phosphorylation states of cell cycle and DNA repair proteins can be altered by the nsSNPs

Background

Sentinel lymph node (SLN) biopsy is an effective tool for axillary staging in patients with invasive breast cancer. This procedure has been recently proposed as part of the treatment for patients with ductal carcinoma in situ (DCIS), because cases of undetected invasive foci and nodal metastases occasionally occur. However, the indications for SLN biopsy in DCIS patients are controversial. The aim of the present study was therefore to assess the incidence of SLN metastases in a series of patients with a diagnosis of pure DCIS.

Methods

A retrospective evaluation was made of a series of 102 patients who underwent SLN biopsy, and had a final histologic diagnosis of pure DCIS. Patients with microinvasion were excluded from the analysis. The patients were operated on in five Institutions between 1999 and 2004. Subdermal or subareolar injection of 30–50 MBq of 99 m-Tc colloidal albumin was used for SLN identification. All sentinel nodes were evaluated with serial sectioning, haematoxylin and eosin staining, and immunohistochemical analysis for cytocheratin.

Results

Only one patient (0.98%) was SLN positive. The primary tumour was a small micropapillary intermediate-grade DCIS and the SLN harboured a micrometastasis. At pathologic revision of the specimen, no detectable focus of microinvasion was found.

Conclusion

Our findings indicate that SLN metastases in pure DCIS are a very rare occurrence. SLN biopsy should not therefore be routinely performed in patients who undergo resection for DCIS. SLN mapping can be performed, as a second operation, in cases in which an invasive component is identified in the specimen. Only DCIS patients who require a mastectomy should have SLN biopsy performed at the time of breast operation, since in these cases subsequent node mapping is not feasible.     

Bone mineral density in women with sarcoidosis

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Almost any organs of the body, but mostly the lungs, are involved. Bone mineral density (BMD) can be affected directly or indirectly in chronic granulomatous systemic diseases such as sarcoidosis. The aim of our study was to evaluate BMD in premenopausal and postmenopausal sarcoidosis patients with or without prednisone treatment and to compare their BMD values with those of a control group having the same menopausal status. Thirty-five premenopausal women (18 untreated, 8 treated, and 9 controls) and 21 postmenopausal women (5 untreated, 5 treated, and 11 controls) were included in the study. All of the patients had a histologically proven diagnosis and were being followed-up at the Sarcoidosis Outpatient Clinic of our unit. BMD of the lumbar (L) spine and femoral neck was measured by dual-energy absorptiometry (DEXA). The subgroups of premenopausals and postmenopausals were compared separately. Comparison among the groups was performed by using analysis of variance. Age, duration of the disease, and body mass index were comparable in treated, untreated, and control subgroups of the pre- and postmenopausal groups, and the subgroups of postmenopausals had comparable durations since menopause. For premenopausals, BMD values at L1–4 were not significantly different among the subgroups (0.920 ± 0.08g/cm², 0.801 ± 0.09g/cm², and 0.910 ± 0.05g/cm², for untreated, treated, and controls, respectively). However, the BMD value at the femoral neck in treated patients (0.921 ± 0.1g/cm²) was significantly lower than the values in untreated patients (1.080 ± 0.2g/cm²; P 0.01) and in controls (1.028 ± 0.17g/cm²; P 0.05). For postmenopausals, the BMD value at L1–4 in controls (1.019 ± 0.07g/cm²) was significantly higher than the values in untreated patients (0.783 ± 0.01g/cm²) and in treated patients (0.751 ± 0.08g/cm²; P 0.001 for both). The BMD value at the femoral neck in controls (0.890 ± 0.1g/cm²) was higher than the values in untreated patients (0.745 ± 0.08g/cm²) and treated patients (0.747 ± 0.1g/cm²), but the difference was not statistically significant (P = 0.06). We concluded that sarcoidosis patients, especially postmenopausal patients with corticosteroid treatment, may have an increased risk of bone mineral loss. Large-scale studies are warranted in order to delineate the exact roles of the disease itself, menopausal status, and corticosteroid treatment in this bone mineral loss.     

Genetic variations as cancer prognostic markers: review and update

Cancer molecular epidemiology traditionally studies the relationship between genetic variations and cancer risk. However, recent studies have also focused on disease outcomes. The application and design of disease outcome studies have been an extension of disease risk assessment. Yet there are a number of unique considerations important in outcome assessments. We review how genetic approaches used for disease susceptibility, such as candidate gene and genome‐wide association study (GWAS) approaches, can be adapted carefully to systematically identify cancer prognostic and predictive alleles. We discuss the interrelatedness among the disease susceptibility, treatment response, and prognosis at the genetic level and focus on how the emerging technologies and approaches can uniquely benefit the genetic prognosis studies. Hum Mutat 30:1–9, 2009. © 2009 Wiley‐Liss, Inc.     

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Clinical Rheumatology -     

iNOS Expression in Oral and Gastrointestinal Tract Mucosa

It is known that the overproduction of nitric oxide (NO) by nitric oxide synthase (NOS) occurs during the progression of various inflammatory diseases in intestinal tract. NOS inhibitors or inducible nitric oxide synthase (iNOS) gene expression inhibitors should be considered as potential anti-inflammatory agents, as NO synthesized by iNOS is related to various pathophysiological processes including inflammation. In order to understand the relationship between iNOS and pathological reactions such as the inflammatory process and malign transformation clearly, the existence and amount of constitutive expression should be determined. It is crucial to comprehend the harmful and protective amounts of iNOS expressions in order to clarify the relationship between iNOS and pathological processes. Evidently, only after this inspection is it possible to utilize iNOS as a marker and treatment instrument during the diagnosis and treatment of malign transformation and the inflammatory process.