Fully automated 3D basal ganglia activity measurement in dopamine transporter scintigraphy (Spectalyzer)

Objectives  

Semiquantitative evaluation of tracer uptake in basal ganglia is superior to visual assessment of images in dopamine transporter (DAT) scintigraphy especially in follow-up of the patients. Manual drawing of regions of interest (ROIs) in two-dimensional (2D) transaxial slices of the single photon emission computed tomography (SPECT) datasets leads to a large inter- and intra-reader variability, while being time consuming. Our aim was to investigate a technique that extracts 3D ROIs in a fully automated fashion and thus might provide reproducible user-independent results allowing better follow-up control and large-scale clinical studies.     

Elevated Levels of T-helper 17-associated Cytokines in Diabetes Type I Patients: Indicators for Following the Course of Disease

Background: Type 1 diabetes (T1D) is thought to involve chronic inflammation, which is manifested by the activation and expression of different inflammatory mediators. Th1- and Th17-associated cytokines are factors that have been shown to exert profound pro-inflammatory activities and have been implicated in the pathogenesis of T1D in mice and humans.

Objectives: Therefore, the aim of this case control study was to determine the serum level of IL-17, IL-21, IL-27, transforming growth factor beta (TGF-β), and IFN-γ and their reciprocal relationship in Iranian T1D patients.

Patients and Methods: Blood samples were collected from 48 T1D patients and 49 healthy individuals with no history of malignancies or autoimmune disorders based on simple sampling. The serum levels of IL-17, IL-21, IL-27, TGF-β, and IFN-γ were measured by the enzyme linked immunosorbent assay (ELISA).

Results: The serum levels of IL-17 and IL-21 were significantly higher in T1D patients compared to the healthy individuals (p = 0.005 and 0.01, respectively), but interestingly, the opposite was the case for IL-27 (p < 0.0001). However, there were no significant differences in TGF-β and IFN-γ between both groups. In addition, IL-17/IFN-γ and IL-17/IL-27 ratios were higher in patients compared to the control group.

Conclusions: Our results indicated dominant Th17-associated IL-17, suggesting a shift from the Treg and Th1 phenotypes toward the Th17 phenotype. Therefore, it can promote inflammation in β cells in T1D. In addition, it suggests the role of Th17 and Th17/Th1 ratios as a potential contributor to β cells destruction and the Th17/Th1 response ratio may provide a novel biomarker for rapid T1D diagnosis before the destruction of β cells and progression of the disease to the clinical end stages.     

Neoadjuvant Dual HER2‐Targeted Therapy With Lapatinib and Trastuzumab Improves Pathologic Complete Response in Patients With Early Stage HER2‐Positive Breast Cancer: A Meta‐Analysis of Randomized Prospective Clinical Trials

Background.

Randomized clinical trials (RCT) that evaluated the addition of lapatinib to trastuzumab plus neoadjuvant chemotherapy (NAC) in patients with HER2-positive, operable breast cancer revealed a questionable improvement in pathologic complete response (pCR) rate. We performed a meta-analysis of prospective RCTs that examined the effect of adding lapatinib to trastuzumab and NAC on pCR rate.

Methods.

PubMed databases and abstracts from the proceedings of the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium were searched for RCTs that compared lapatinib plus trastuzumab and NAC with trastuzumab in combination with NAC and that included pCR as the primary outcome. Our main objective was to estimate the effect of adding lapatinib to trastuzumab plus NAC on pCR rate, defined as no residual invasive cancer in breast and axillary lymph nodes.

Results.

In total, 1,017 patients with early stage breast cancer from 5 trials were included. Four trials examined the addition of lapatinib to trastuzumab plus NAC; this resulted in statistically significant improvement in pCR, defined as no residual carcinoma in breast and lymph nodes. The pCR rate was 55.76% and 38.36% in the lapatinib plus trastuzumab and the trastuzumab plus NAC arms, respectively (odds ratio [OR]: 1.94; 95% confidence interval [CI]: 1.44–2.60). In three trials, the rates of pCR, defined as no residual invasive carcinoma in breast only, for the lapatinib plus trastuzumab and trastuzumab-alone groups were 55.01% and 40.70%, respectively, also resulting in significant improvement (OR: 1.78; 95% CI: 1.27–2.50).

Conclusion.

The addition of lapatinib to trastuzumab in combination with neoadjuvant chemotherapy significantly improves pCR rates in patients with HER2-positive breast cancer.     

Sarcoidosis with multiple organ involvement and uncommon symptoms: A case report

Sarcoidosis is a complicated inflammatory disease characterized by the formation of non‐caseating epithelioid granulomas in many organs. Herein, we reported a sarcoidosis case with multiple organ involvements and our diagnostic criteria and treatment plan.     

Identification of 3{alpha}-hydroxy-cyproterone acetate as a metabolite of cyproterone acetate in the bile of female rats and the potential of this and other already known or putative metabolites to form DNA adducts in vitro

Cyproterone acetate (CPA) is a synthetic steroid hormone usedin the therapy of prostate cancer in men and different formsof acne and hirsutism in women. CPA has been shown by ³²P-postlabelinganalysis to bind covalently to hepatic DNA of rats in vivo andin vitro. A prerequisite for DNA adduct formation of CPA ismetabolic activation of the drug to a reactive intermediate.In the present study bile was collected from [³H]CPA-treatedfemale rats and, following chromatographic separation of bileextracts, fractions of the eluate were examined for the presenceof reactive metabolites which were able to form adducts withcalf thymus DNA in vitro. The formation of adducts was detectedby ³²P-postlabeling analysis. One major metabolite of CPA presentin the bile extracts was isolated and, following a thoroughstructural elucidation by mass spec-trometry and ¹H-NMR, thismetabolite was identified as 3     

Pro-oxidant–antioxidant balance in Iranian veterans with sulfur mustard toxicity and different levels of pulmonary disorders

Objective: Sulfur mustard (SM) is a strong alkylating agent that primarily targets the skin, eye and lung. The current study evaluated the pro-oxidant–antioxidant balance (PAB) assay in human serum of SM-exposed patients. Design and methods: sera of 35 SM-exposed patients and 19 healthy volunteers were recruited. Both groups had nonsmoker and nonalcoholic people with no diseases such as diabetes, heart disease and other pulmonary diseases (COPD because of smoking, asthma and so on). All patients had documented exposure to SM. The PAB was measured. Results: SM-exposed patients with normal values for pulmonary function test and severe obstructive pulmonary disease demonstrated a significant increase in PAB value in compared with healthy volunteers (the PAB values in healthy volunteers, normal and severe patients were 48.74?±?21.07 HK, 101.45?±?32.68 HK and 120.23?±?31.55 HK, respectively). However, the level of oxidation is not related to the severity of disease defined by spirometry findings. A significant negative correlation was established between the PAB value and FEV₁.

Conclusions: The increased PAB value in chemical casualties showed that these patients are exposed to oxidative stress.     

One year outcomes after glucose-insulin-potassium in ST elevation myocardial infarction. The Glucose-insulin-potassium study II

BackgroundThere are conflicting data concerning the effect of treatment with glucose–insulin–potassium (GIK) in ST segment elevation myocardial infarction (STEMI). Early studies showed beneficial effects of GIK, however, recent large sample size trials did not confirm this, or suggested only benefits in patients without heart failure. We aimed to evaluate long-term effects of GIK in patients with STEMI without signs of heart failure, all treated with reperfusion therapy.MethodsFrom August 2003 to December 2004, 889 STEMI patients without signs of heart failure were randomized to standard care (N = 445) or additional GIK infusion (N = 444). Glucose–potassium (20% glucose with 80 mmol potassium/l) was infused at 2 ml/kg body weight per hour for 12 h through a peripheral line. Short-acting insulin was started according to admission glucose and adjusted based on hourly measured glucose. Clinical end points were of number of death, reinfarction and revascularization at 1 year.ResultsOne year follow-up was available in 864 patients (97.2%), 432 in the GIK group and 432 in the control group. Mortality rate was 5.3% in GIK and 3.9% in control patients, p = 0.33. Rates of reinfarction and revascularization 4.6% vs. 4.6% and 15.5% and 15.0%, in GIK vs. control patients.ConclusionIn patients with STEMI without signs of heart failure treated with reperfusion therapy, GIK therapy offers no clinical benefit at 1 year.     

Routine upstream versus selective down stream use of tirofiban in non-ST elevation myocardial infarction patients scheduled for early invasive therapy; a randomized comparison

Background Despite their proven beneficial effects and inclusion in the guidelines, glycoprotein (GP) IIb/IIIA blockers are underused in daily practice in patients with non ST-segment elevation acute coronary syndrome (NSTE ACS). This study combines the data from two randomized controlled trials, comparing routine upstream versus selective down stream use of tirofiban in patients with NSTE ACS. Methods Inclusion criteria for both studies (ELISA-1 and 2) were angina pectoris, with ST depression >1 mm and or a positive cardiac biomarkers. All patients were scheduled for coronary angiography. The primary and secondary end points for both studies were enzymatic infarct size (LDHQ48) and initial TIMI flow of the culprit lesion respectively. Results From August 2000 to January 2005, 273 patients were randomized to routine upstream tirofiban and 275 patients to selective down stream use of tirofiban. Selective down stream tirofiban was used in 55 patients (20%). Patients in the upstream group more often had a patent culprit lesion (65% vs. 50%, P=0.003) and a significantly smaller enzymatic infarct size, LDHQ48 median (25–75%): 125 (55–309) vs. 189 (68–504) IU/l, P=0.006 as compared to the selective down stream group. Subgroup analysis showed that routine upstream tirofiban was particularly effective in males, patients with a positive troponin on admission and in those not pretreated with clopidogrel. Conclusion Routine upstream GP IIb/IIIa is mainly effective in patients with elevated troponin on admission and those not pretreated with clopidogrel. Large scale randomized trials are needed to evaluate the effect of GP IIb/IIIa blockers on top of clopidogrel pretreatment on major adverse cardiac events.