Successful Endomyocardial Biopsy Guided by Transthoracic Two-Dimensional Echocardiography

Introduction. Two-dimensional (2-D) echocardiography is an excellent alternative method to perform endomyocardial biopsies (EB) in special situations, mainly when the patient is in a critical state and cannot go to the catheterization laboratory or when there are contraindications to the use of fluoroscopy as in the pregnancy. Objective. This single-center experience analyzed the last 25 years use of an EB technique guided by echocardiography realized at the bedside on critical patients. Methods. From 1985 to 2010, we performed 76 EB guided by 2-D echocardiography on 59 patients, among whom 38 (64.4%) were critically ill with examinations at the bedside; among 10 (16.9%) subjects, the procedure was carried out simultaneously with fluoroscopy for safety`s sake during the learning period. In addition, 8 (13.6%) were unavailable for fluoroscopy, and 3 (5.1%) required a hybrid method due to an intracardiac tumor. Results. The main adverse effects included local pain (n = 4, 5.6%); difficult out successful puncture due to previous biopsies (n = 4, 5.6%); local hematoma without major consequences (n = 3, 4.2%); failed but ultimately successful puncture on the first try due to previous biopsies or (n = 3, 4.2%); obesity and immediate postoperative period with impossibility to pass the bioptome into the right ventricle; however 2 days later the procedure was repeated successfully by echocardiography (n = 1, 1.4%). All myocardial specimens displayed suitable size. There were no undesirable extraction effects on the tricuspid valve tissue. In this series, there was no case of death, hemopericardium, or other major complication as a direct consequence of the biopsy. Conclusion. 2-D echocardiography is a special feature to guide EB is mainly in critically ill patients because it can be performed at the bedside without additional risk or disadvantages of fluoroscopy. The hybrid method associating 2-D echocardiography and fluoroscopy allows the procedure in different situations such as intracardiac tumor cases.

Dipyridamole Stress and Rest Myocardial Perfusion by 64-Detector Row Computed Tomography in Patients With Suspected Coronary Artery Disease

Recently, stress myocardial computed tomographic perfusion (CTP) was shown to detect myocardial ischemia. Our main objective was to evaluate the feasibility of dipyridamole stress CTP and compare it to single-photon emission computed tomography (SPECT) to detect significant coronary stenosis using invasive conventional coronary angiography (CCA; stenosis >70%) as the reference method. Thirty-six patients (62 +/- 8 years old, 20 men) with previous positive results with SPECT (<2 months) as the primary inclusion criterion and suspected coronary artery disease underwent a customized multidetector-row CT protocol with myocardial perfusion evaluation at rest and during stress and coronary CT angiography (CTA). Multidetector-row computed tomography was performed in a 64-slice scanner with dipyridamole stress perfusion acquisition before a second perfusion/CT angiographic acquisition at rest. Independent blinded observers performed analysis of images from CTP, CTA, and CCA. All 36 patients completed the CT protocol with no adverse events (mean radiation dose 14.7 +/- 3.0 mSv) and with interpretable scans. CTP results were positive in 27 of 36 patients (75%). From the 9 (25%) disagreements, 6 patients had normal coronary arteries and 2 had no significant stenosis (8 false-positive results with SPECT, 22%). The remaining patient had an occluded artery with collateral flow confirmed by conventional coronary angiogram. Good agreement was demonstrated between CTP and SPECT on a per-patient analysis (kappa 0.53). In 26 patients using CCA as reference, sensitivity, specificity, and positive and negative predictive values were 88.0%, 79.3%, 66.7%, and 93.3% for CTP and 68.8, 76.1%, 66.7%, and 77.8%, for SPECT, respectively (p = NS). In conclusion, dipyridamole CT myocardial perfusion at rest and during stress is feasible and results are similar to single-photon emission CT scintigraphy. The anatomical-perfusion information provided by this combined CT protocol may allow identification of false-positive results by SPECT. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:310-315)

Evaluation of fly ash as a component of potting substrates

A series of laboratory and glasshouse experiments were undertaken to assess the potential for incorporation of fly ash in soilless potting substrates. The physical and chemical properties of a commercially available bark based substrate, the University of California (UC) 1:1 peat:sand mix and a range uf test substrates containing fly ash were characterised. In test mixtures, fly ash was substituted for a portion of either the peat or sand component of the UC mix, at rates of 10, 20, 30 and 50% of the mix volume, Incorporation of fly ash greatly increased the plant available water capacity (10-1500 kPa) of the substrate. However, high pH, increased substrate strength and reduced air-filled porosity were considered adverse effects, particularly at ash rates > 20%. The growth of tomato (Lycopersicon esculentum), petunia (Petunia x hybrida grandiflora) and Boston fern (Nephrolepis exaltata) in the substrates was assessed. Two watering regimes, capillary watering and irregular hosing, were used to identify effects of available water capacity on plant growth, but no effect was identified. Test mixtures containing fly ash as 20% of the substrate volume produced growth equal to that in the UC mix, with substrates containing 10% ash producing significantly greater growth of tomato and petunia. At rates of incorporation > 20% reduced plant growth was attributed to both adverse physical and chemical characteristics of the substrate. As fly ash is available at low cost and can be successfully substituted for a considerable portion of the expensive peat component, its use at low application rates in potting substrates may be desirable from an economic viewpoint.

Mammaplasty with Inferior Pedicle Flap After Massive Weight Loss

After massive weight loss, one of the stigmas that afflict women is the remaining deformity of the breasts which become flaccid and ptotic, with an absent or flat upper pole. The authors propose the use of a well-established mammaplasty technique to fill the upper pole, reshape the breast cone, and correct ptosis with nipple-areola complex (NAC) repositioning. A total of 16 patients were analyzed; all underwent gastroplasty between 18 and 24 months prior to mammaplasty. The mean age was 41.6 years (range = 26-62) and the mean BMI previous to the mammaplasty was 29.2 kg/m(2) (range = 24.9-38.9). The technique included a dermo-lipo glandular flap pedicled on the inframammary fold (IMF) together with a superior flap containing the NAC. All patients who underwent surgery were satisfied with the outcomes since a more aesthetic breast shape was achieved, with projection of the upper pole and correction of ptosis. Adverse events included dehiscence at the junction point of the flaps in the inframammary fold, which resolved with secondary-intention wound healing in three patients; partial necrosis of the areola in one patient; epidermolysis in one of the NACs in one patient; and infection in one of the breasts in one patient, which resolved with proper antibiotic therapy. When compared to the current mammaplasty techniques performed in formerly obese patients, this is a good surgical option because it uses tissues adjacent to the breast itself and does not require silicone prosthesis for breast augmentation. The patients reported increased self-esteem and improvement in their quality of life.

Effect of creatine supplementation on measured glomerular filtration rate in postmenopausal women

We aimed to investigate whether creatine supplementation affects the measured glomerular filtration rate in postmenopausal women (age, 58 +/- 3 years). Subjects were randomly assigned to receive either creatine (20 g(.)day(-1) for 1 week and 5 g(.)day(-1) thereafter) or a placebo. Kidney function was assessed at baseline and after 12 weeks. [(51)Cr] EDTA clearance remained unchanged (CR-PRE: 86.16 +/- 14.36 mL(.)min(-1) per 1.73 m(2), POST: 87.25 +/- 17.60 mL(.)min(-1) per 1.73 m(2); PL-PRE: 85.15 +/- 8.54 mL(.)min(-1) per 1.73 m(2), POST: 87.18 +/- 9.64 mL(.)min(-1) per 1.73 m(2); p = 0.81). Thus, we concluded that creatine supplementation does not affect glomerular filtration rate in postmenopausal women.

Creatine in Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial

GUALANO, B., V. DE. SALLES PAINNELI, H. ROSCHEL, G. G. ARTIOLI, M. NEVES JR, A. L. DE SA PINTO, M. E. DA SILVA, M. R. CUNHA, M. C. G. OTADUY, C. DA COSTA LEITE, J. C. FERREIRA, R. M. PEREIRA, P. C. BRUM, E. BONFA, and A. H. LANCHA JR. Creatine in Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial. Med. Sci. Sports Exerc., Vol. 43, No. 5, pp. 770-778, 2011. Creatine supplementation improves glucose tolerance in healthy subjects. Purposes: The aim was to investigate whether creatine supplementation has a beneficial effect on glycemic control of type 2 diabetic patients undergoing exercise training. Methods: A 12-wk randomized, double-blind, placebo-controlled trial was performed. The patients were allocated to receive either creatine (CR) (5 g.d(-1)) or placebo (PL) and were enrolled in an exercise training program. The primary outcome was glycosylated hemoglobin (Hb(A1c)). Secondary outcomes included the area under the curve of glucose, insulin, and C-peptide and insulin sensitivity indexes. Physical capacity, lipid profile, and GLUT-4 protein expression and translocation were also assessed. Results: Twenty-five subjects were analyzed (CR: n = 13; PL: n = 12). Hb(A1c) was significantly reduced in the creatine group when compared with the placebo group (CR: PRE = 7.4 +/- 0.7, POST = 6.4 +/- 0.4; PL: PRE = 7.5 +/- 0.6, POST = 7.6 +/- 0.7; P = 0.004; difference = -1.1%, 95% confidence interval = -1.9% to -0.4%). The delta area under the curve of glucose concentration was significantly lower in the CR group than in the PL group (CR = -7790 +/- 4600, PL = 2008 +/- 7614; P = 0.05). The CR group also presented decreased glycemia at times 0, 30, and 60 min during a meal tolerance test and increased GLUT-4 translocation. Insulin and C-peptide concentrations, surrogates of insulin sensitivity, physical capacity, lipid profile, and adverse effects were comparable between the groups. Conclusions: Creatine supplementation combined with an exercise program improves glycemic control in type 2 diabetic patients. The underlying mechanism seems to be related to an increase in GLUT-4 recruitment to the sarcolemma.

The placebo effect and homeopathy

Background: Like other forms of medicine, including Complementary and Alternative Medicine (CAM), homeopathy elicits expectations in patients. The physician-patient relationship, personal and comprehensive treatment and lack of adverse effects are elements in creating positive expectations. Other elements may be associated with negative expectations. Methods: We conducted a systematic literature review on placebo and nocebo effects in acupuncture and homeopathy using Medline. Results: Findings on the psychophysiological and neuromediating mechanisms of the placebo-nocebo phenomenon are reviewed. Studies of these effects reveal how expectations and unconscious conditioning can be measured by imaging and EEG methods. They result in significant, non-specific therapeutic effects, which may confuse the evaluation of the specific therapeutic effects treatment, hampering selection of the simillimum. Conclusions: Directions for future research on non-specific therapeutic effects of homeopathy to improve clinical practice and clinical research are discussed. Homeopathy (2010) 99, 119-129.

Outcomes and safety of drug provocation tests

Drug provocation tests (DPTs) are considered the gold standard for identifying adverse drug reactions (ADRs). The aim of this study was to analyze DPT results and discuss severe systemic reactions associated with them. This was a retrospective analysis of 500 patients with ADRs who sought treatment and were submitted to DPTs when indicated between 2006 and 2010. We performed DPTs according to the European Network for Drug Allergy recommendations. Single-blind, placebo-controlled DPTs were performed with antibiotics, local anesthetics, and nonsteroidal anti-inflammatory drugs, as well as with other drugs. Patient characteristics, DPT results, and reactions were analyzed. The sample comprised 198 patients (80.8% of whom were female patients) submitted to 243 DPTs. Ages ranged from 9 to 84 years (mean, 39.9 years). The 243 DPTs were performed with local anesthetics (n = 93), antibiotics (n = 19), acetaminophen (n = 44), benzydamine (n = 33), COX-2 inhibitors (n = 26), dipyrone (n = 7), aspirin (n = 4), or other drugs (n = 17). The results of 4 tests (1.6%) were inconclusive, whereas those of 10 (4.1%) revealed positive reactions to antibiotics (2/19), COX-2 inhibitors (2/26), acetaminophen (3/44), and local anesthetics (3/93). Two severe reactions were observed: cephalexin-induced anaphylactic shock and bupivacaine-induced anaphylaxis without shock. Four patients (2.0%) reacted to the placebo before administration of the drug. Drug provocation tests are safe for use in clinical practice but they should be placebo-controlled and should be performed under the supervision of an allergist. To confirm a presumptive diagnosis and to manage allergies appropriately, it is crucial to perform DPTs. (Allergy Asthma Proc 32:301-306, 2011; doi: 10.2500/aap.2011.32.3450)

Effect of the Novel Thienopyridine Prasugrel Compared With Clopidogrel on Spontaneous and Procedural Myocardial Infarction in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 An Application of the Classification System From the Universal Definition of Myocardial Infarction

Background-Prasugrel is a novel thienopyridine that reduces new or recurrent myocardial infarctions (MIs) compared with clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention. This effect must be balanced against an increased bleeding risk. We aimed to characterize the effect of prasugrel with respect to the type, size, and timing of MI using the universal classification of MI. Methods and Results-We studied 13 608 patients with acute coronary syndrome undergoing percutaneous coronary intervention randomized to prasugrel or clopidogrel and treated for 6 to 15 months in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction (TRITON-TIMI 38). Each MI underwent supplemental classification as spontaneous, secondary, or sudden cardiac death (types 1, 2, and 3) or procedure related (Types 4 and 5) and examined events occurring early and after 30 days. Prasugrel significantly reduced the overall risk of MI (7.4% versus 9.7%; hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.67 to 0.85; P < 0.0001). This benefit was present for procedure-related MIs (4.9% versus 6.4%; HR, 0.76; 95% CI, 0.66 to 0.88; P = 0.0002) and nonprocedural (type 1, 2, or 3) MIs (2.8% versus 3.7%; HR, 0.72; 95% CI, 0.59 to 0.88; P = 0.0013) and consistently across MI size, including MIs with a biomarker peak >= 5 times the reference limit (HR. 0.74; 95% CI, 0.64 to 0.86; P = 0.0001). In landmark analyses starting at 30 days, patients treated with prasugrel had a lower risk of any MI (2.9% versus 3.7%; HR, 0.77; P = 0.014), including nonprocedural MI (2.3% versus 3.1%; HR, 0.74; 95% CI, 0.60 to 0.92; P = 0.0069). Conclusion-Treatment with prasugrel compared with clopidogrel for up to 15 months in patients with acute coronary syndrome undergoing percutaneous coronary intervention significantly reduces the risk of MIs that are procedure related and spontaneous and those that are small and large, including new MIs occurring during maintenance therapy. (Circulation. 2009; 119: 2758-2764.)

Lepocreadiid (Digenea) species from members of the marine teleost family Cheilodactylidae from south-western Australia, including four new genera and five new species

The following lepocreadiid species are described from Cheilodactylidae from south-western Australia. Cliveus peroni n. g., n. sp, from Nemadactylus valenciennesi is characterised by its attenuated forebody and C. acaenodera n. sp. from Dactylophora nigricans by its attenuated forebody, the pattern of forebody spination and the large cirrus-sac. Jericho chojeri n. g., n. sp. from N. valenciennesi has a large infundibuliform oral sucker and paired ani. Rugocavum n. g. is distinguished by the possession of a blind, wrinkled glandular pit on the postero-ventral surface of the forebody. R. nemadactyli n. sp. from N. valenciennesi has its vitelline field restricted to the hindbody, whereas in R. morwong n. sp, from N. valenciennesi the vitelline field reaches into the forebody. Paraneocreadium australiense Kruse, 1978 from N. valenciennesi is redescribed and its coiled internal seminal vesicle and lobed gonads are considered distinctive features. Scaphatrema nemadactyli (Kurochkin & Korotaeva, 1972) n. g., n. comb. from N. valenciennesi has a wrinkled, boat-shaped body, a 'Lepidapedon-like' cirrus-sac and multiple testes; it was originally placed in the genus Multitestis, but these characters suggest that a new genus should be erected for it within the subfamily Lepidapedinae.

Double-blind, Randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: Results from EFECT

Purpose The third-generation nonsteroidal aromatase inhibitors (AIs) are increasingly used as adjuvant and first-line advanced therapy for postmenopausal, hormone receptor-positive (HR +) breast cancer. Because many patients subsequently experience progression or relapse, it is important to identify agents with efficacy after AI failure. Materials and Methods Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) is a randomized, double-blind, placebo controlled, multicenter phase III trial of fulvestrant versus exemestane in postmenopausal women with HR + advanced breast cancer (ABC) progressing or recurring after nonsteroidal AI. The primary end point was time to progression (TTP). A fulvestrant loading-dose (LD) regimen was used: 500 mg intramuscularly on day 0, 250 mg on days 14, 28, and 250 mg every 28 days thereafter. Exemestane 25 mg orally was administered once daily. Results A total of 693 women were randomly assigned to fulvestrant (n = 351) or exemestane ( n = 342). Approximately 60% of patients had received at least two prior endocrine therapies. Median TTP was 3.7 months in both groups ( hazard ratio = 0.963; 95% CI, 0.819 to 1.133; P = .6531). The overall response rate ( 7.4% v 6.7%; P = .736) and clinical benefit rate ( 32.2% v 31.5%; P = .853) were similar between fulvestrant and exemestane respectively. Median duration of clinical benefit was 9.3 and 8.3 months, respectively. Both treatments were well tolerated, with no significant differences in the incidence of adverse events or quality of life. Pharmacokinetic data confirm that steady-state was reached within 1 month with the LD schedule of fulvestrant. Conclusion Fulvestrant LD and exemestane are equally active and well-tolerated in a meaningful proportion of postmenopausal women with ABC who have experienced progression or recurrence during treatment with a nonsteroidal AI.

Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial

Background Treatment with adjuvant trastuzumab for 1 year improves disease-free survival and overall survival in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We aimed to assess disease-free survival and overall survival after a median follow-up of 4 years for patients enrolled on the Herceptin Adjuvant (HERA) trial. Methods The HERA trial is an international, multicentre, randomised, open-label, phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard neoadjuvant, adjuvant chemotherapy, or both in patients with HER2-positive early breast cancer. The primary endpoint was disease-free survival. After a positive first interim analysis at a median follow-up of 1 year for the comparison of treatment with trastuzumab for 1 year with observation, event-free patients in the observation group were allowed to cross over to receive trastuzumab. We report trial outcomes for the 1-year trastuzumab and observation groups at a median follow-up of 48.4 months (IQR 42.0-56.5) and assess the effect of the extensive crossover to trastuzumab. Our analysis was by intention-to-treat. The HERA trial is registered with the European Clinical Trials Database, number 2005-002385-11. Findings The HERA trial population comprised 1698 patients randomly assigned to the observation group and 1703 to the 1-year trastuzumab group. Intention-to-treat analysis of disease-free survival showed a significant benefit in favour of patients in the 1-year trastuzumab group (4-year disease-free survival 78.6%) compared with the observation group (4-year disease-free survival 72.2%; hazard ratio [HR] 0.76; 95% CI 0.66-0.87; p<0.0001). Intention-to-treat analysis of overall survival showed no significant difference in the risk of death (4-year overall survival 89.3% vs 87.7%, respectively; HR 0.85; 95% CI 0.70-1.04; p=0.11). Overall, 885 patients (52%) of the 1698 patients in the observation group crossed over to receive trastuzumab, and began treatment at median 22.8 months (range 4.5-52.7) from randomisation. In a non-randomised comparison, patients in the selective-crossover cohort had fewer disease-free survival events than patients remaining in the observation group (adjusted HR 0.68; 95% CI 0.51-0.90; p=0.0077). Higher incidences of grade 3-4 and fatal adverse events were noted on 1-year trastuzumab than in the observation group. The most common grade 3 or 4 adverse events, each in less than 1% of patients, were congestive cardiac failure, hypertension, arthralgia, back pain, central-line infection, hot flush, headache, and diarrhoea. Interpretation Treatment with adjuvant trastuzumab for 1 year after chemotherapy is associated with significant clinical benefit at 4-year median follow-up. The substantial selective crossover of patients in the observation group to trastuzumab was associated with improved outcomes for this cohort.

Guanosine promotes B16F10 melanoma cell differentiation through PKC-ERK 1/2 pathway

Malignant melanoma is one of the most lethal cancers. Nowadays, several anti-melanoma therapies have been employed. However, the poor prognosis and/or the increased toxicity of those treatments clearly demonstrate the requirement of searching for new drugs or novel combined chemotherapeutic protocols, contemplating both effectiveness and low toxicity. Guanosine (Guo) has been used in combination with acriflavina to potentiate the latter`s antitumor activity, through still unknown mechanisms. Here, we show that Guo induces B16F10 melanoma cell differentiation, attested by growth arrest, dendrite-like outgrowth and increased melanogenesis, and also reduced motility. A sustained ERK 1/2 phosphorylation was observed after Guo treatment and ERK inhibition led to blockage of dendritogenesis. Intracellular cyclic AMP was not involved in ERK activation, since its levels remained unchanged. Protein kinase C (PKC), in contrast to phospholipase C (PLC), inhibition completely prevented ERK activation. While the classical melanoma differentiation agent forskolin activates cAMP-PKA-Raf-MEK-ERK pathway in B16F10 cells, here we suggest that a cAMP-independent, PKC-ERK axis is involved in Guo-induced B16F10 differentiation. Altogether, our results show that Guo acts as a differentiating agent, with cytostatic rather than cytotoxic properties, leading to a decreased melanoma malignancy. Thus, we propose that Guo may be envisaged in combination with lower doses of conventional anti-melanoma drugs, in an attempt to prevent or diminish their adverse effects. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Linear IgA dermatosis induced by pregnancy

Linear IgA disease is a rare autoimmune subepidermal bullous disorder characterized by linear IgA deposits at the epidermal basement membrane zone. According to the literature, in patients who have linear IgA disease and become pregnant, the disease tends to improve. We report a case of linear IgA disease induced by pregnancy, successfully treated with dapsone and prednisone with no adverse effects observed in the patient and her newborns.

Effect of Weight Loss on Aerobic Capacity in Patients with Severe Obesity Before and After Bariatric Surgery

Severe obesity has been associated with adverse effects on physical capacity. In a prospective study, the aerobic capacity of severely obese patients was measured in order to observe the physiological response to weight loss from bariatric surgery. Sixty-five consecutive patients (40.4 +/- 8.4 years old; 93.8% female; body mass index = 49.4 +/- 5.4 kg/m(2)) were evaluated before bariatric surgery and then 6 and 12 months after surgery. Aerobic capacity was assessed with a scientific treadmill to measure maximal oxygen consumption (VO(2max)), heart rate, blood pressure, time on the treadmill, and distance walked (modified Bruce test). For the three observational periods, VO(2max) was 25.4 +/- 9.3, 29.8 +/- 8.1, and 36.7 +/- 8.3 ml/kg/min; time on the treadmill was 5.4 +/- 1.4, 6.4 +/- 1.6, and 8.8 +/- 1.0 min; and distance walked was 401.8 +/- 139.1, 513.4 +/- 159.9, and 690.5 +/- 76.2 m. For these variables, significant results (p = 0.0000) were observed for the two postoperative periods in relation to the preoperative period. Severely obese individuals increased their aerobic capacity after successful bariatric surgery. The data also suggests that a positive and progressive relationship between weight loss and improvement in fitness as a moderate loss of weight 6 months after surgery already showed some benefit and an additional reduction in weight was associated with a better performance in the aerobic capacity tests at the 12-month follow-up.