Conversion from Cystine to Noncystine Stones: Incidence and Associated Factors.

PURPOSE: Patients with cystinuria are often treated with medical alkalization and shock wave lithotripsy, although each treatment is hypothesized to increase the risk of calcium phosphate stones. We performed a multicenter retrospective review to evaluate whether stones of another composition develop in patients with cystinuria and with what frequency. MATERIALS AND METHODS: We retrospectively reviewed the records of a multi-institutional cohort of patients with cystinuria. We assessed medications, stone analyses, 24-hour urinalyses and types of procedures. We compared patients who formed only cystine stones vs those with noncystine stones. RESULTS: We identified 125 patients from a total of 5 institutions who were followed a mean of 5.2 years (range 0 to 26). Stones with noncystine components were submitted by 37 patients (29.6%). Potassium citrate medication was not associated with a noncystine composition (p = 0.1877). Regarding surgical management 18 patients (13%) underwent at least 1 shock wave lithotripsy session (range 0 to 9) and 79 (63%) underwent percutaneous nephrolithotomy at least once (range 0 to 10). When stratified based on pure cystine vs converted stones, the average total number of shock wave lithotripsy and percutaneous nephrolithotomy procedures was higher in the group with cystine and subsequent noncystine stone compositions (0.94 vs 0.10, p <0.0001, and 1.7 vs 1.5, p = 0.0053, respectively). On logistic regression male gender (OR 3.1, p = 0.0280) and the number of shock wave lithotripsy sessions (OR 3.0, p = 0.0170) were associated with an increased likelihood of the development of stones with a noncystine composition. CONCLUSIONS: Stones with noncystine components develop in more than 25% of patients with cystinuria, underscoring the importance of continued stone analysis. In this study prior shock wave lithotripsy was associated with conversion to a noncystine stone composition while urinary alkalization therapy was not associated.

A combination of p300 and Braf expression in the diagnosis and prognosis of melanoma.

BACKGROUND: To date only a handful of drugs are available for the treatment of melanoma. Among them vemurafenib, a BrafV600E specific inhibitor, showed promising results in terms of response rate and increase in median survival time. However, its effectiveness is limited by development of resistance and the search for additional drugs for melanoma treatment is ongoing. The present study was performed to analyze the correlation between Braf expression and the expression of p300, a known down stream target of the mitogen activated protein kinase (MAPK) pathway, which was recently shown by us to be a prognostic marker for melanoma progression and patient survival. METHODS: The expression of Braf and p300 expression were correlated and analyzed by Chi-square test. A total of 327 melanoma patient cases (193 primary melanoma and 134 metastatic melanoma) were used for the study. Classification & regression tree (CRT), Kaplan-Meier, and multivariate Cox regression analysis were used to elucidate the significance of the combination of Braf and p300 expression in the diagnosis and prognosis of melanoma. RESULTS: Our results demonstrate that Braf expression is inversely correlated with nuclear p300 and positively correlated with cytoplasmic p300 expression. Braf and cytoplasmic p300 were found to be associated with melanoma progression, tumor size and ulceration status. CRT analysis revealed that a combination of Braf and p300 expression (nuclear and cytoplasmic), could be used to distinguish between nevi and melanoma, and primary from metastatic melanoma lesions. The combination of Braf and nuclear p300 was significantly associated with patient survival and nuclear p300 was found to be an independent predictor of patient survival. CONCLUSION: Our results indicate a cross-talk between Braf and p300 in melanoma and demonstrate the importance Braf and p300 expression in the diagnosis and prognosis of melanoma.

Pleiotropic function of SRY-related HMG box transcription factor 4 in regulation of tumorigenesis.

In addition to their critical roles in embryonic development, cell fate decision, and differentiation, members of Sox (Sry-related high-mobility group box) family of transcription factors including Sox4 have been implicated in various cancers. Multiple studies have revealed an increased expression along with specific oncogenic function of Sox4 in tumors, while others observed a reduced expression of Sox4 in different types of malignancies and suppression of tumor initiation or progression by this protein. More interestingly, the prognostic value of Sox4 is debated due to obvious differences between various reports as well as inconsistencies within specific studies. This review summarizes our current understanding of Sox4 expression pattern and its transcription-dependent, as well as transcription-independent, functions in tumor initiation or progression and its correlation with patient survival. We also discuss the existing discrepancies between different reports and their possible explanations.

Stage-specific prognostic biomarkers in melanoma.

The melanoma staging system proposed by the American Joint Committee on Cancer (AJCC) (which classifies melanoma patients into four clinical stages) is currently the most widely used tool for melanoma prognostication, and clinical management decision making by clinicians. However, multiple studies have shown that melanomas within specific AJCC Stages can exhibit varying progression and clinical outcomes. Thus, additional information, such as that provided by biomarkers is needed to assist in identifying the patients at risk of disease progression. Having previously found six independent prognostic biomarkers in melanoma, including BRAF, MMP2, p27, Dicer, Fbw7 and Tip60, our group has gone on to investigate if these markers are useful in risk stratification of melanoma patients in individual AJCC stages. First, we performed Kaplan-Meier survival and Cox proportional multivariate analyses comparing prognostication power of these markers in 254 melanoma patients for whom the expression levels were known, identifying the best performing markers as candidates for stage-specific melanoma markers. We then verified the results by incorporating an additional independent cohort (87 patients) and in a combined cohort (341 patients). Our data indicate that BRAF and MMP2 are optimal prognostic biomarkers for AJCC Stages I and II, respectively (P = 0.010, 0.000, Log-rank test); whereas p27 emerged as a good marker for AJCC Stages III/IV (0.018, 0.046, respectively, log-rank test). Thus, our study has identified stage-specific biomarkers in melanoma, a finding which may assist clinicians in designing improved personalized therapeutic modalities.

Effects of opium addiction on bleeding after coronary artery bypass graft surgery: report from Iran.

PURPOSE: Opium abuse is a major type of drug abuse in Iran. This study was designed to find the possible relation between opium addiction and excessive bleeding after coronary artery bypass graft (CABG) surgery. METHODS: In a historical cohort study during a 1.5-year period, consecutive patients scheduled for elective CABG surgery were assigned to two group on the basis of having or not having the criteria for inhalational opium addiction. Before and after operations, the complete blood count, bleeding time, prothrombin time, partial thromboplastin time, and platelet count were checked for all patients. The volumes of infused red blood cells during and after the operation were recorded. After operations, the volumes of bleeding through the patients' chest tubes were recorded. The recorded data were analyzed using SPSS software version 11.5. Independent t, chi-square and repeated measure tests were used; and P < 0.05 was considered statistically significant. RESULTS: In total, 84 nonaddicted patients were assigned in group 1, and 110 patients who fulfilled the addiction criteria were assigned in group 2. Total bleeding from the three chest tubes was significantly different between the two groups (P = 0.001). The mean hemoglobin level, prothrombin time, partial thromboplastin time, and platelet counts before and after the operations were similar in the two groups. Opium-addicted patients received more packed red blood cells during and after the operations. CONCLUSION: Inhalational opium addiction might lead to more hemorrhage after CABG surgery. It is recommended that cardiac surgeons consider these patients at high risk for major complications after surgery.

Impact of psoriasis on quality of life in Iran.

BACKGROUND: The Psoriasis Disability Index (PDI) questionnaire is a widely used instrument to measure psychological morbidity in plaque-type psoriasis patients. AIMS: This study aimed to validate the Persian version of the PDI and to evaluate the impact of psoriasis on quality of life (QOL). METHODS: The English language version of the PDI was translated into Persian (Iranian official language) and was used in this study. The questionnaire was administered to a consecutive sample of 125 chronic plaque-type psoriasis patients and statistical analysis was performed to evaluate the impact of psoriasis on QOL. The other health-related QOL assessment tool included the Persian version of the Dermatology Life Quality Index (DLQI). RESULTS: Overall, 125 patients who had received the PDI and DLQI completed all the questions. Reliability analysis showed a satisfactory result (Cronbach's a coefficient=0.92 and 0.79 for PDI and DLQI, respectively). There was a strong statistical correlation between mean PDI and DLQI scores, with mean Psoriasis Area and Severity Index (PASI) (P=0.005 and 0.02). Also, a significant correlation coefficient existed between DLQI and PDI (r=0.94). The higher the PASI index, the higher the PDI and DLQI scores, which indicated greater impact on QOL. In the patients with lesions on visible exposed skin areas, the correlation was statistically significant (P=0.002 and 0.01). CONCLUSION: The Persian PDI is an acceptable, reliable and valid measure of psychological distress, with more suitable content validity than DLQI for assessment of impact of psoriasis on QOL among psoriasis patients. Data provided may improve the physicians' awareness of the importance of the patients' QOL.

Topical immunotherapy with diphenylcyclopropenone in vitiligo: a preliminary experience.

BACKGROUND: Despite recent significant therapeutic advances, vitiligo remains a clinical conundrum. Topical immunotherapy has been extensively tested in the treatment of various dermatologic disorders, especially those believed to have an immunologic basis. AIM: To evaluate the role of topical diphenylcyclopropenone (DPCP) in the treatment of vitiligo. METHODS: Nineteen patients with limited vitiligo lesions were enrolled in this study. After sensitization with 2% lotion of DPCP in acetone, progressively higher concentrations beginning at 0.001% up to 2% were applied weekly for 6 months to the depigmented skin lesions. RESULTS: Thirteen of the 19 patients were evaluated at the end of 6 months. Four patients with focal vitiligo, one patient with vitiligo vulgaris, and three patients with segmental vitiligo showed marked (grade 3) repigmentation. CONCLUSION: Marginal and central repigmentation with hyperpigmented borders was seen in the majority of lesions. Further controlled trials should be undertaken to evaluate the use of topical DPCP in vitiligo.

Retinoic acid synergistically enhances the melanocytotoxic and depigmenting effects of monobenzylether of hydroquinone in black guinea pig skin.

Monobenzylether of hydroquinone (MBEH) has long been utilized for the depigmentation therapy of patients with extensive vitiligo. In this approach, the normally pigmented areas surrounding vitiligo lesions are depigmented to achieve a uniform skin tone. One of the important disadvantages of MBEH therapy, however, is the resistance of a considerable number of vitiligo patients against the depigmenting effect of this agent. We have previously proposed that the glutathione-dependent cytoprotection of melanocytes can be impaired through the inhibition of the enzyme glutathione S-transferase by retinoic acid (RA). The combination of RA with melanocytotoxic agents could thus lead to increased susceptibility of melanocytes to such compounds. In this study we have shown, for the first time, that the melanocytotoxic and depigmenting effects of MBEH are synergistically enhanced when it is combined with RA. The treatment of black guinea pig skin with RA (0.025%) alone induced no significant changes in the number of epidermal melanocytes and no skin depigmentation. On the other hand, MBEH (10%) produced mild to moderate skin depigmentation and reduced the average number of melanocytes from 76 (+/-5)/field (magnification: x 40) in control sites, to 42 (+/-6)/field in the depigmented skin. The RA (0.025%)-MBEH (10%) combination, however, produced a complete degree of depigmentation in the majority of treated sites after 10 days of application and reduced the average number of melanocytes to only 6 (+/-6)/field. RA-MBEH combination serves as a very potent skin depigmenting formula and now awaits future assessments of its potential use for the treatment of extensive vitiligo.