Evaluation of quality of life related to i-131 therapy in patients with well-differentiated thyroid cancer and emphasis in salivary morbidity: a follow up study after treatment

To evaluate the impact of iodine-131 therapy received during childhood and adolescence and correlate it with the quality of life in these patients. Methods: We studied 19 patients diagnosed with cancer in childhood or adolescence who underwent thyroidectomy and supplemental therapy with I-131. We also recruited a control group of healthy subjects with the same demographic parameters. All patients were subjected to a scintigraphy examination of the salivary glands, and were also asked to complete a questionnaire in order to assess their overall quality of life. In addition, a more specific questionnaire for patients with head and neck cancer was also given to all study participants. Results: The quantitative and qualitative analyses of the salivary glands showed functional deficits with greater involvement of the parotid gland for volume, concentration and excretion. The right submandibular gland showed significant changes for volume in the patient group. The questionnaires made it possible to observe significant differences between the patient and control groups for symptoms such as thick saliva, dry mouth and speech problems. Conclusion: In spite of being very effective and widely used, iodine radionuclide therapy is correlated with a lower quality of life in young people.

Sterilization of immature blowflies (Calliphoridae) for use in larval therapy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Potent Antiretroviral Therapy for Human Immunodeficiency Virus Infection Increases Aortic Stiffness

Background: Highly active antiretroviral therapy for AIDS is known to increase cardiovascular risk, but the effects of potent antiretroviral agents according to gender are unknown. Objective: The present study evaluated the impact of HIV infection treatment on aortic stiffness according to gender. Methods: From university-affiliated hospitals, we recruited 28 AIDS patients undergoing highly active antiretroviral treatment (HAART), 28 treatment-naive HIV-infected patients, 44 patients with type 2 diabetes, and 30 controls. Aortic stiffness was determined by measuring pulse wave velocity (PWV) using a validated and non-invasive automatic device. Results: The crude mean PWV values and 95% confidence intervals (95% CI) for HAART, diabetics, and controls were 9.77 m/s (95% CI 9.17-10.36),, 9.00 m/s (95% CI 8.37-9.63), 9.90 m/s (95% CI 9.32-10.49), and 9.28 m/s (95% CI 8.61-9.95), respectively, for men (P-value for trend = 0.14), and 9.61 m/s (95% CI 8.56-10.66), 8.45 m/s (95% CI 7.51-9.39), 9.83 (95% CI 9.21-10.44), and 7.79 m/s (95% CI 6.99-8.58), respectively, for women (P-value for trend <0.001). Post-hoc analysis revealed a significant difference between the mean PWV values in the HAART group and controls in women (P-value <0.01). After adjusting for other potential covariates, including systolic blood pressure and diabetes, these results did not change. The findings indicate that the impact of HAART treatment on aortic stiffness was amplified in women with hypertension, dyslipidemia, and metabolic syndrome. Conclusion: Potent anti-retroviral agents used in the treatment of HIV infection increases aortic stiffness, mainly among women with higher cardiovascular risk. (Arq Bras Cardiol 2012;99(6):1100-1107)

A Randomized, Naturalistic, Parallel-Group Study for the Long-Term Treatment of Panic Disorder With Clonazepam or Paroxetine

This long-term extension of an 8-week randomized, naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam (n = 47) and paroxetine (n = 37) over a 3-year total treatment duration. Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine (both taken at bedtime). This study reports data from the long-term period (34 months), following the initial 8-week treatment phase. Thus, total treatment duration was 36 months. Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine, but patients with partial primary treatment success were switched to the combination therapy. At initiation of the long-term study, the mean doses of clonazepam and paroxetine were 1.9 (SD, 0.30) and 38.4 (SD, 3.74) mg/d, respectively. These doses were maintained until month 36 (clonazepam 1.9 [ SD, 0.29] mg/d and paroxetine 38.2 [SD, 3.87] mg/d). Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)-Improvement rating than treatment with paroxetine (mean difference: CGI-Severity scale -3.48 vs -3.24, respectively, P = 0.02; CGI-Improvement scale 1.06 vs 1.11, respectively, P = 0.04). Both treatments similarly reduced the number of panic attacks and severity of anxiety. Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine (28.9% vs 70.6%, P < 0.001). The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course. There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events.

Influenza A/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy?

Objective. To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens. Methods. A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) epsilon 20 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination. Results. The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED epsilon 20 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED epsilon 20 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED epsilon 20 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED epsilon 20 mg + IS + CQ (57.4%; P = 0.09). Conclusion. Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity.

Surrogate endpoints for prostate cancer-specific mortality after radiotherapy and androgen suppression therapy in men with localised or locally advanced prostate cancer: an analysis of two randomised trials

Background Androgen suppression therapy and radiotherapy are used to treat locally advanced prostate cancer. 3 years of androgen suppression confers a small survival benefit compared with 6 months of therapy in this setting, but is associated with more toxic effects. Early identification of men in whom radiotherapy and 6 months of androgen suppression is insufficient for cure is important. Thus, we assessed whether prostate-specific antigen (PSA) values can act as an early surrogate for prostate cancer-specific mortality (PCSM). Methods We systematically reviewed randomised controlled trials that showed improved overall and prostate cancer-specific survival with radiotherapy and 6 months of androgen suppression compared with radio therapy alone and measured lowest PSA concentrations (PSA nadir) and those immediately after treatment (PSA end). We assessed a cohort of 734 men with localised or locally advanced prostate cancer from two eligible trials in the USA and Australasia that randomly allocated participants between Feb 2, 1996, and Dec 27, 2001. We used Prentice criteria to assess whether reported PSA nadir or PSA end concentrations of more than 0.5 ng/mL were surrogates for PCSM. Findings Men treated with radiotherapy and 6 months of androgen suppression in both trials were significantly less likely to have PSA end and PSA nadir values of more than 0.5 ng/mL than were those treated with radiotherapy alone (p<0.0001). Presence of candidate surrogates (ie, PSA end and PSA nadir values >0.5 ng/mL) alone and when assessed in conjunction with the randomised treatment group increased risk of PCSM in the US trial (PSA nadir p=0.0016; PSA end p=0.017) and Australasian trial (PSA nadir p<0.0001; PSA end p=0.0012). In both trials, the randomised treatment group was no longer associated with PCSM (p >= 0.20) when the candidate surrogates were included in the model. Therefore, both PSA metrics satisfied Prentice criteria for surrogacy. Interpretation After radiotherapy and 6 months of androgen suppression, men with PSA end values exceeding 0.5 ng/mL should be considered for long-term androgen suppression and those with localised or locally advanced prostate cancer with PSA nadir values exceeding 0.5 ng/mL should be considered for inclusion in randomised trials investigating the use of drugs that have extended survival in castration-resistant metastatic prostate cancer.

Histomorphometric analysis of inflammatory response and necrosis in re-implanted central incisor of rats treated with low-level laser therapy

Low-level laser therapy is a tool employed in the management of post-operative inflammation process and in the enhancement of reparative process. The aim of the study was to perform histological evaluation of dental and periodontal ligament of rats central upper-left incisor teeth re-implanted and irradiated with low-level laser (InGaAl, 685 nm, 50 J/cm(2)) 15, 30, and 60 days after re-implantation. Seventy-two male rats had the central upper left incisor removed and kept for 15 min on dry gauze before replantation. Laser was irradiated over the root surface and empty alveolus prior replantation and over surrounding mucosa after the re-implantation. After histological procedures, all slices were analyzed regarding external resorption area and histological aspects. We observed an increase of root resorption (p < 0.05) in the control group compared to the laser group at 15, 30, and 60 days. These results showed that the laser groups developed less root resorption areas than the control group in all experimental periods. Additionally, histological analysis revealed less inflammatory cells and necrotic areas in laser groups.

Treatment effects of bonded spurs associated with high-pull chincup therapy in the treatment of patients with anterior open bite

Introduction: The aim of this prospective clinical study was to investigate the cephalometric changes produced by bonded spurs associated with high-pull chincup therapy in children with Angle Class I malocclusion and anterior open bite. Methods: Thirty patients with an initial mean age of 8.14 years and a mean anterior open bite of -3.93 mm were treated with bonded spurs associated with chincup therapy for 12 months. An untreated control group of 30 subjects with an initial mean age of 8.36 years and a mean anterior open bite of -3.93 mm and the same malocclusion was followed for 12 months for comparison. Student t tests were used for intergroup comparisons. Results: The treated group demonstrated a significantly greater decrease of the gonial angle, and increase in overbite, palatal tipping of the maxillary incisors, and vertical dentoalveolar development of the maxillary and mandibular incisors compared with the control group. Conclusions: The association of bonded spurs with high-pull chincup therapy was efficient for the correction of the open bite in 86.7% of the patients, with a 5.23-mm (SD, +/- 1.69) overbite increase. (Am J Orthod Dentofacial Orthop 2012;142:487-93)

Low Level Laser Therapy as an Adjunctive Technique In the Management of Temporomandibular Disorders

The purpose of this study was to assess the effect of low level laser therapy on subjects with intra-articular temporomandibular disorders (IA-TMD), and to quantify and compare severity of signs and symptoms before, during, and after the laser applications. The sample consisted of 45 subjects randomly divided into three groups (G) of 15 subjects each: G-I: 15 individuals with IA-TMD submitted to an energy dose of 52.5 J/cm(2); G-II: dose of 105.0 J/cm(2); and G-III: placebo group (0 J/cm(2)). In all groups, the applications were performed on condylar points on the masseter and anterior temporalis muscles. Two weekly sessions were held for five weeks, totaling 10 applications. The assessed variables were: mandibular movements and painful symptoms evoked by muscle palpation. These variables were measured before starting the study, then immediately after the first, fifth, and tenth laser application, and finally, 32 days after completing the applications. The results showed that there were statistically significant differences for G-I and G-II at the level of 1% between the doses, as well as between assessments. Therefore, it was concluded that the use of low level laser increased the mean mandibular range of motion and reduced painful symptoms in the groups that received effective treatment, which did not occur in the placebo group.

Effect of low-level laser therapy after rapid maxillary expansion on proliferation and differentiation of osteoblastic cells

The aim of this study was to investigate the osteoblastic activity of cells derived from the midpalatal suture upon treatment with low-level laser therapy (LLLT) after rapid maxillary expansion (RME). A total of 30 rats were divided into two groups: experimental I (15 rats with RME without LLLT) and experimental II (15 rats with RME + LLLT). The rats were euthanized at 24 h, 48 h, and 7 days after RME, when the osteoblastic cells derived from the rats' midpalatal suture were explanted. These cells were cultured for periods up to 17 days, and then in vitro osteogenesis parameters and gene expression markers were evaluated. The cellular doubling time in the proliferative stage (3-7 days) was decreased in cultured cells harvested from the midpalatal suture at 24 and 48 h after RME + LLLT, as indicated by the increased growth of the cells in a culture. Alkaline phosphatase activity at days 7 and 14 of the culture was increased by LLLT in cells explanted from the midpalatal suture at 24 and 48 h and 7 days after RME. The mineralization at day 17 was increased by LLLT after RME in all periods. Results from the real-time PCR demonstrated that cells harvested from the LLLT after RME group showed higher levels of ALP, Runx2, osteocalcin, type I collagen, and bone sialoprotein mRNA than control cells. More pronounced effects on ALP activity, mineralization, and gene expression of bone markers were observed at 48 h after RME and LLLT. These results indicate that the LLLT applied after RME is able to increase the proliferation and the expression of an osteoblastic phenotype in cells derived from the midpalatal suture.

Endostatin gene therapy stimulates upregulation of ICAM-1 and VCAM-1 in a metastatic renal cell carcinoma model

One of the greatest challenges in urological oncology is renal cell carcinoma (RCC), which is the third leading cause of death in genitourinary cancers. RCCs are highly vascularized and respond positively to antiangiogenic therapy. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we examined the potential of ES-based antiangiogenic therapy to activate tumor-associated endothelial cells in metastatic RCC (mRCC). Balb/c-bearing Renca cells were treated with NIH/3T3-LendSN or, as a control, with NIH/3T3-LXSN cells. The T-cell subsets and lymphocyte populations of tumors, mediastinal lymph nodes and the spleen were assessed by flow cytometry. The expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was assessed by real-time PCR, flow cytometry and immunohistochemistry analysis. ES gene therapy led to an increase in the percentage of infiltrating CD4-interferon (IFN)-gamma cells (P<0.05), CD8-IFN-gamma cells (P<0.01) and CD49b-tumor necrosis factor-alpha cells (P<0.01). In addition, ES therapy caused an increase at the mRNA level of ICAM-1 (1.4-fold; P<0.01) and VCAM-1 (1.5-fold) (control vs treated group; P<0.001). Through flow cytometry, we found a significant increase in the CD34/ICAM-1 cells (8.1-fold; P<0.001) and CD34/VCAM-1 cells (1.6-fold; P<0.05). ES gene therapy induced a significant increase in both T CD4 and CD8 cells in the lymph nodes and the spleen, suggesting that ES therapy may facilitate cell survival or clonal expansion. CD49b cells were also present in increased quantities in all of these organs. In this study, we demonstrate an antitumor inflammatory effect of ES in an mRCC model, and this effect is mediated by an increase in ICAM-1 and VCAM-1 expression in tumor-associated endothelial cells.

Gray Matter Volumes in Obsessive-Compulsive Disorder Before and After Fluoxetine or Cognitive-Behavior Therapy: A Randomized Clinical Trial

Serotonin reuptake inhibitors and cognitive-behavior therapy (CBT) are considered first-line treatments for obsessive-compulsive disorder (OCD). However, little is known about their modulatory effects on regional brain morphology in OCD patients. We sought to document structural brain abnormalities in treatment-naive OCD patients and to determine the effects of pharmacological and cognitive-behavioral treatments on regional brain volumes. Treatment-naive patients with OCD (n = 38) underwent structural magnetic resonance imaging scan before and after a 12-week randomized clinical trial with either fluoxetine or group CBT. Matched-healthy controls (n = 36) were also scanned at baseline. Voxel-based morphometry was used to compare regional gray matter (GM) volumes of regions of interest (ROIs) placed in the orbitofrontal, anterior cingulate and temporolimbic cortices, striatum, and thalamus. Treatment-naive OCD patients presented smaller GM volume in the left putamen, bilateral medial orbitofrontal, and left anterior cingulate cortices than did controls (p<0.05, corrected for multiple comparisons). After treatment with either fluoxetine or CBT (n = 26), GM volume abnormalities in the left putamen were no longer detectable relative to controls. ROI-based within-group comparisons revealed that GM volume in the left putamen significantly increased (p<0.012) in fluoxetine-treated patients (n = 13), whereas no significant GM volume changes were observed in CBT-treated patients (n = 13). This study supports the involvement of orbitofronto/cingulo-striatal loops in the pathophysiology of OCD and suggests that fluoxetine and CBT may have distinct neurobiological mechanisms of action. Neuropsychopharmacology (2012) 37, 734-745; doi: 10.1038/npp.2011.250; published online 26 October 2011

Mimosine and Cyclophosphamide: a Potential New Combination Therapy Used to Prevent Tumor Development

The effects of mimosine (MI), which is an amino acid that is derived from Leucaena leucocephala, were evaluated on the growth of ascitic Ehrlich tumors, and the effects of the combination treatment of MI and cyclophosphamide (CY) on tumor growth were also assessed. Mice were divided into groups that received the following treatments over the course of 20 days: phosphate buffer solution (CO), MI, Ehrlich cells (E), E plus CY (EC), E plus MI (EM) and E plus MI and CY (EMC). No signs of toxicity were detected in the mice from the MI group. The mice from the EMC group showed reductions in body weights when compared with those from the E group. The animals from the EC, EM and EMC groups showed reductions in ascitic volume compared with those from the E group. The mice from the EMC group showed reductions in total cell numbers of ascitic fluid compared with those from the E, EC and EM groups. The combination of MI and CY was the most effective treatment for Ehrlich tumor ascites.

Infrared (810 nm) Low-Level Laser Therapy in Experimental Model of Strain-Induced Skeletal Muscle Injury in Rats: Effects on Functional Outcomes

Muscle strains are among the most prevalent causes for athletes absence from sport activities. Low-level laser therapy (LLLT) has recently emerged as a potential contender to nonsteroidal anti-inflammatory drugs in muscle strain treatment. In this work we investigated effects of LLLT and diclofenac on functional outcomes in the acute stage after muscle strain injury in rats. Muscle strain was induced by overloading the tibialis anterior muscle of rats during anesthesia. The injured groups received either no treatment, or a single treatment with diclofenac 30 min prior to injury, or LLLT (810 nm, 100 mW) with doses of 1, 3, 6 or 9 J, at 1 h after injury. Functional outcome measures included a walking index and assessment of electrically induced muscle performance. All treatments (except 9 J LLLT) significantly improved the walking index 12 h postinjury compared with the untreated group. The 3 J group also showed a significantly better walking index than the drug group. All treatments significantly improved muscle performance at 6 and 12 h. LLLT dose of 3 J was as effective as the pharmacological agent in improving functional outcomes in the early phase after a muscle strain injury in rats.

Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma

Melanoma cells express the platelet-activating factor receptor (PAFR) and, thus, respond to PAF, a bioactive lipid produced by both tumour cells and those in the tumour microenvironment such as macrophages. Here, we show that treatment of a human melanoma SKmel37 cell line with cisplatin led to increased expression of PAFR and its accumulation. In the presence of exogenous PAF, melanoma cells were significantly more resistant to cisplatin-induced cell death. Inhibition of PAFR-dependent signalling pathways by a PAFR antagonist (WEB2086) showed chemosensitisation of melanoma cells in vitro. Nude mice were inoculated with SKmel37 cells and treated with cisplatin and WEB2086. Animals treated with both agents showed significantly decreased tumour growth compared to the control group and groups treated with only one agent. PAFR accumulation and signalling are part of a prosurvival program of melanoma cells, therefore constituting a promising target for combination therapy for melanomas.