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1.
Pharmazie ; 76(9): 444-449, 2021 09 01.
Article in English | MEDLINE | ID: mdl-34481536

ABSTRACT

The use of azacitidine (AZA) has been known to lead to a high incidence of hematotoxic adverse events. The aims of this study were to identify the risk factors for thrombocytopenia after the administration of AZA and to analyze time to the initial platelet transfusion. Sixty-two patients with myelodysplastic syndrome (MDS), who were treated with AZA in Gifu Municipal Hospital between March 2012 and June 2020, were included in this study. The risk factors for thrombocytopenia were identified using univariate analysis of patient characteristics, disease type, and laboratory values immediately before the start of treatment. Variables with p<0.2 identified in the univariate analysis were used as independent variables in the multivariate analysis. This analysis identified "creatinine clearance (CCr) <60 mL/min" as a significant factor (odds ratio, 4.790; 95% confidence interval [CI], 1.380-16.70; p=0.014). Subsequently, time in days to the initial platelet transfusion after the initial administration of AZA was analyzed using the log-rank test. The overall median time in days to platelet transfusion was 370 days. The log-rank test was used to determine the influence of patient characteristics, disease type, and laboratory values immediately before the start of treatment. The subsequent Cox proportional hazard regression analysis using variables with p<0.2 as independent variables identified "hemoglobin (Hb) <8.0 g/dL" as a significant factor (hazard ratio, 2.143; 95% CI, 1.001-4.573; p=0.048). The results of this study led to the following clinical implications: first, patients with CCr of <60 mL/min at the start of treatment should be treated with caution due to the risk of thrombocytopenia. Second, patients with Hb of <8.0 g/dL at the start of treatment may require platelet transfusion in the early stage of treatment.


Subject(s)
Myelodysplastic Syndromes , Thrombocytopenia , Azacitidine/adverse effects , Humans , Myelodysplastic Syndromes/chemically induced , Myelodysplastic Syndromes/drug therapy , Platelet Transfusion/adverse effects , Risk Factors , Thrombocytopenia/chemically induced , Thrombocytopenia/drug therapy , Thrombocytopenia/epidemiology
2.
Pharmazie ; 76(6): 279-286, 2021 06 01.
Article in English | MEDLINE | ID: mdl-34078523

ABSTRACT

A high proportion of hospitalizations is attributable to the prevalence of adverse drug events. This retrospective study included outpatients and inpatients to determine the prevalence of adverse drug events and if polypharmacy increases it. The prevalence, classification, and causality of adverse drug events were assessed based on medical records, laboratory values, and other data. Multivariate analysis (multiple logistic regression analysis) was performed with the presence or absence of adverse drug events at the time of the visit as the dependent variable and items for which the P-value was <0.25 in the univariate analysis as independent variables. The prevalence of adverse drug events was 13.0%, 10.9%, and 16.0% among all patients, the outpatient group, and the inpatient group, respectively. Multivariate analysis showed that polypharmacy (≥5 drugs) significantly increased the risk of adverse drug events in all patients. The prevalence of adverse drug events significantly increased with each additional drug used. We expect that minimizing the number of medications through moderation of the number of prescription drugs and elimination of polypharmacy will reduce the number of outpatient visits and hospitalizations due to adverse drug events.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Outpatients , Drug-Related Side Effects and Adverse Reactions/epidemiology , Hospitalization , Humans , Polypharmacy , Prevalence , Retrospective Studies
3.
Eur J Neurol ; 28(1): 314-322, 2021 01.
Article in English | MEDLINE | ID: mdl-32889770

ABSTRACT

OBJECTIVE: To investigate changes in serum complements and their regulators in the pathogenesis of myasthenia gravis (MG). METHODS: Forty-four patients with acetylcholine receptor antibody-positive MG, as well as 20 patients with non-inflammatory neurological disorders were enrolled. Serum complements (C3, C4 and soluble C5b-9) and complement regulators (vitronectin, clusterin and properdin) were extensively analysed by enzyme-linked immunosorbent assay and their associations with clinical profiles of MG were examined. RESULTS: Serum C3, C4 and clusterin levels were not significantly different between patients with MG and controls. The patients with MG had higher soluble C5b-9 (P = 0.09) and vitronectin (P = 0.001) levels than the controls; moreover, vitronectin levels decreased after treatment (P = 0.09). Serum properdin (P = 0.03) levels were lower in the patients with MG than in the controls, and negatively correlated with the MG Activities of Daily Living score (rs = -0.26, P = 0.09) and with the presence of bulbar palsy (P = 0.04). CONCLUSION: Our results show that activation of complements and an altered complement network could contribute to the inflammatory pathogenesis of MG.


Subject(s)
Activities of Daily Living , Myasthenia Gravis , Autoantibodies , Complement System Proteins , Humans , Receptors, Cholinergic
4.
Clin Exp Immunol ; 203(3): 366-374, 2021 03.
Article in English | MEDLINE | ID: mdl-33184844

ABSTRACT

Myasthenia gravis (MG) is characterized by muscle weakness and fatigue caused by the presence of autoantibodies against the acetylcholine receptor (AChR) or the muscle-specific tyrosine kinase (MuSK). Activated T, B and plasma cells, as well as cytokines, play important roles in the production of pathogenic autoantibodies and the induction of inflammation at the neuromuscular junction in MG. Many studies have focused on the role of cytokines and lymphocytes in anti-AChR antibody-positive MG. Chronic inflammation mediated by T helper type 17 (Th17) cells, the promotion of autoantibody production from B cells and plasma cells by follicular Th (Tfh) cells and the activation of the immune response by dysfunction of regulatory T (Treg ) cells may contribute to the exacerbation of the MG pathogenesis. In fact, an increased number of Th17 cells and Tfh cells and dysfunction of Treg cells have been reported in patients with anti-AChR antibody-positive MG; moreover, the number of these cells was correlated with clinical parameters in patients with MG. Regarding cytokines, interleukin (IL)-17; a Th17-related cytokine, IL-21 (a Tfh-related cytokine), the B-cell-activating factor (BAFF; a B cell-related cytokine) and a proliferation-inducing ligand (APRIL; a B cell-related cytokine) have been reported to be up-regulated and associated with clinical parameters of MG. This review focuses on the current understanding of the involvement of cytokines and lymphocytes in the immunological pathogenesis of MG, which may lead to the development of novel therapies for this disease in the near future.


Subject(s)
Cytokines/immunology , Myasthenia Gravis/immunology , T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunology , Animals , Autoantibodies/immunology , B-Lymphocytes/immunology , Cytokines/metabolism , Humans , Myasthenia Gravis/metabolism , Receptor Protein-Tyrosine Kinases/immunology , Receptors, Cholinergic/immunology , Th17 Cells/metabolism
5.
Clin Exp Immunol ; 202(3): 321-324, 2020 12.
Article in English | MEDLINE | ID: mdl-32706905

ABSTRACT

Myasthenia gravis (MG) is an autoantibody-mediated inflammatory disease of the neuromuscular junction. Biomarkers indicating disease activity in MG are warranted. Recently, the soluble urokinase plasminogen activator receptor (suPAR) has been reported to be associated with inflammation, tissue damage, disease activity and prognosis in various diseases, including autoimmune diseases. In this study, serum suPAR levels were measured in 40 patients with anti-acetylcholine receptor antibody-positive MG and 30 controls, and their correlations with clinical variables and severity scale scores were investigated. We identified that serum suPAR levels significantly correlated with MG activities of daily living scale (Spearman's ρ = 0·45; P = 0·004) and MG Foundation of America classification (Spearman's ρ = 0·37; P = 0·02) at serum sampling, but not with anti-acetylcholine receptor antibody titers. In conclusion, serum suPAR levels can be a candidate for a novel biomarker of disease activity in anti-acetylcholine receptor antibody-positive MG.


Subject(s)
Myasthenia Gravis , Receptors, Urokinase Plasminogen Activator , Severity of Illness Index , Aged , Biomarkers/blood , Female , Humans , Male , Middle Aged , Myasthenia Gravis/blood , Myasthenia Gravis/immunology , Pilot Projects , Receptors, Urokinase Plasminogen Activator/blood , Receptors, Urokinase Plasminogen Activator/immunology
6.
QJM ; 113(9): 691-692, 2020 Sep 01.
Article in English | MEDLINE | ID: mdl-31917415
8.
Eur J Neurol ; 27(1): 175-180, 2020 01.
Article in English | MEDLINE | ID: mdl-31347231

ABSTRACT

BACKGROUND AND PURPOSE: Thymectomy is an effective treatment for myasthenia gravis (MG) with anti-acetylcholine receptor (AChR) antibodies. We rarely encounter patients who develop MG after surgery for thymic tumors. This study aimed to investigate the characteristics and frequency of post-thymectomy onset (PostTx) MG. METHODS: We reviewed the clinical information of thymoma-associated MG in 158 patients. Of these, 18 (11%) patients with PostTx MG were identified. RESULTS: The presence of anti-AChR antibodies (82%) and electrophysiological abnormalities (50%) was confirmed before thymectomy in patients with PostTx MG. The clinical characteristics of PostTx MG were similar to those of pre-thymectomy onset (PreTx) MG. In PostTx MG, the duration between thymectomy and MG onset were distributed as < 6 months (early-onset PostTx MG) and ≥ 6 months (late-onset PostTx MG). Notably, some patients with late-onset PostTx MG were associated with thymoma relapse. CONCLUSION: Our results suggest that approximately 11% of patients with thymoma-associated MG were PostTx MG and pre-surgical assessment of anti-AChR antibody titer or electrophysiological testing may predict PostTx MG development. However, no difference in clinical manifestation and prognosis was observed between PreTx MG and PostTx MG.


Subject(s)
Myasthenia Gravis/epidemiology , Myasthenia Gravis/surgery , Postoperative Complications/epidemiology , Thymectomy , Adolescent , Adult , Aged , Aged, 80 and over , Autoantibodies/analysis , Child , Electrophysiological Phenomena , Female , Humans , Male , Middle Aged , Myasthenia Gravis/immunology , Prognosis , Receptors, Cholinergic/immunology , Retrospective Studies , Thymoma/complications , Thymoma/surgery , Thymus Neoplasms/complications , Thymus Neoplasms/surgery , Treatment Outcome , Young Adult
9.
Pharmazie ; 74(7): 439-442, 2019 07 01.
Article in English | MEDLINE | ID: mdl-31288902

ABSTRACT

Chemotherapy for cancer is increasingly implemented in the outpatient setting. Pharmacists contribute to cancer treatment by conducting counseling during outpatient chemotherapy visits. They provide guidance on drug treatment, side effects, and side effect countermeasures on every visit. However, there have been few economic evaluations of pharmacist involvement in outpatient chemotherapy. Therefore, we performed a cost utility analysis. We assigned usual care (control) and pharmacist counseling to two groups of 19 patients receiving outpatient chemotherapy for breast cancer at Gifu Municipal hospital. Quality of life was measured at three timepoints before and during chemotherapy treatment using the EuroQol 5 dimension instrument (EQ-5D). EQ-5D values across the timepoints were 0.831, 0.757, and 0.791 for the control group, and 0.882, 0.883, and 0.921 for the pharmacist counseling group. The additional cost in the pharmacist counseling group was 2,227 yen per counseling session. The change in quality-adjusted life years (QALY) was a maximum of -0.021±0.186 in the control group and 0.007±0.199 in the pharmacist counseling group. The maximum cost for one QALY was 1,360,558 yen (≈12,460 US dollars). Pharmacists' counseling in outpatient cancer chemotherapy for breast cancer patients had an acceptable incremental cost-effect ratio, contributing to improved patient quality of life without significant additional expenditure to healthcare.


Subject(s)
Antineoplastic Agents/administration & dosage , Breast Neoplasms/drug therapy , Pharmacists/organization & administration , Pharmacy Service, Hospital/organization & administration , Adult , Aged , Cost-Benefit Analysis , Counseling/economics , Counseling/methods , Female , Humans , Japan , Middle Aged , Outpatients , Pharmacists/economics , Pharmacy Service, Hospital/economics , Professional Role , Quality of Life , Quality-Adjusted Life Years
10.
Pharmazie ; 74(6): 374-382, 2019 06 01.
Article in English | MEDLINE | ID: mdl-31138377

ABSTRACT

We retrospectively investigated the renal function index of patients with type 2 diabetes mellitus (T2DM) to examine the influence of dipeptidyl peptidase-4 (DPP-4) inhibitors on renal function between patients up to early nephropathy and after overt nephropathy. Patients with T2DM (>18 years old) who had been prescribed hypoglycemic agents for ≥3 months at Gifu Municipal Hospital between March 2010 and April 2014 were included in the study. Renal function was evaluated as the estimated glomerular filtration rate (eGFR) decline from baseline at 12 months. Patients in the DPP-4 inhibitor-treated and untreated groups with an eGFR ≥60 (358 [58.2 %] and 257 [41.8 %], respectively) and eGFR <60 (115 [60.2 %] and 76 [39.8 %], respectively) were subjected to multiple logistic regression analysis. Among patients with an eGFR ≥60, no significant differences were observed in eGFR decline rates over time. However, among patients with an eGFR <60, significant decreases were observed in eGFR decline rates >10 % (6 months; odds ratio, 0.476; P = 0.043, 12 months; odds ratio, 0.413; P = 0.010). Similar results were obtained for an eGFR decline rate >20 % (12 months; odds ratio, 0.369; P = 0.049). DPP-4 inhibitors are renoprotective in patients with T2DM and an eGFR <60.


Subject(s)
Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Glomerular Filtration Rate/drug effects , Aged , Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Female , Humans , Hypoglycemic Agents/pharmacology , Kidney Diseases , Male , Middle Aged , Retrospective Studies
11.
Pharmazie ; 74(12): 760-762, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31907119

ABSTRACT

Cardiovascular surgery is a highly invasive intervention that is often performed in elderly patients at risks of complications because of malnutrition and reduced immunity. This study investigated nutritional factors that affected length of hospital stay in patients undergoing cardiovascular surgery. Among 68 patients who underwent surgery at the Department of Cardiovascular Surgery of Gifu Municipal Hospital between April 2013 and March 2015, 55 with complete data were included in the analysis. Data on serum albumin (ALB), transferrin (Tf), pre-albumin (PA) and retinol binding protein (RBP) levels were collected. The median length of hospital stay was 29 days (stays of ≥30 days were considered long-term hospitalization). Multivariate analysis (multiple logistic regression) included age (≥ 65 years), sex (female), and ALB (≤ 3.0 g/dL), Tf (≤ 150.0 mg/dL), PA (≤ 10.0 mg/dL) and RBP (≤ 1.5 mg/dL) levels. ALB [odds ratio (OR) 10.37, 95% CI (confidence interval): 1.185-90.80, P = 0.035] and Tf [OR 4.743, 95% CI: 1.375-16.36, P = 0.014] were significantly associated with length of hospital stay. Nutritional management of patients and careful monitoring of ALB and Tf levels can shorten length of hospital stay in patients undergoing cardiovascular surgery.


Subject(s)
Cardiovascular Surgical Procedures , Hospitalization , Length of Stay , Nutritional Status , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Nutrition Assessment , Serum Albumin/analysis , Transferrin/analysis
12.
Pharmazie ; 73(10): 598-604, 2018 10 01.
Article in English | MEDLINE | ID: mdl-30223925

ABSTRACT

Over-the-counter (OTC) drugs and health foods/supplements are used as means of self-medication with the aim of preventing diseases and maintaining health. No reports have yet addressed the relationship between healthcare systems and self-medication. Here, we carried out a retrospective survey to identify healthcare system factors affecting OTC drug and health food/supplement usage. Patients hospitalized at Gifu Municipal Hospital between October 1, 2014 and March 31, 2015 were given a survey. The items surveyed were age, gender, disease, alcohol intake/smoking status, insurance classification, and medical pharmaceuticals, OTC drugs, and health foods/supplements used immediately before hospitalization. We performed multiple logistic regression analysis using OTC drugs and health foods/supplements as dependent variables with patient attributes, medical insurance, etc. as independent variables. A total of 5,965 patients were analyzed. OTC users comprised 2.6 % (156 people) of the total. The use of OTC drugs was significantly higher for females and alcohol consumers than in other categories. In contrast, the use of OTC drugs was significantly lower for participants in public expense/medical subsidy programs. Health foods/supplements were used by 4.0 % of all subjects (240 people); their use was significantly higher among females and users of medical pharmaceuticals. On the other hand, the use of health foods/supplements was significantly lower for smokers, users of the latter-stage elderly healthcare system, and users of public expense/medical subsidy programs.


Subject(s)
Dietary Supplements/statistics & numerical data , Drug Utilization/statistics & numerical data , Nonprescription Drugs/administration & dosage , Aged , Delivery of Health Care/statistics & numerical data , Diet/statistics & numerical data , Female , Humans , Retrospective Studies , Self Medication/statistics & numerical data , Sex Factors , Socioeconomic Factors , Surveys and Questionnaires
13.
Cytopathology ; 29(3): 254-261, 2018 06.
Article in English | MEDLINE | ID: mdl-29626374

ABSTRACT

INTRODUCTION: Positive peritoneal cytology (PPC) in endometrial cancer remains a controversial topic. Cleaved caspase-3 (CC3) and Ki-67 are excellent markers of apoptotic and proliferating cells, respectively. The objective of this study was to determine the significance of CC3 and Ki-67 expression in peritoneal cytology samples as prognostic factors for endometrial cancer with PPC. METHODS: Sixty endometrial cancer specimens with PPC alone were divided into 51 endometrioid tumours (43 endometrioid carcinomas and eight carcinomas with squamous differentiation) and nine non-endometrioid tumours (two serous carcinomas, three clear cell carcinomas and four carcinosarcomas). CC3 and Ki-67 expression in peritoneal cytology samples were immunocytochemically assessed and correlated with disease-free survival (DFS) and overall survival (OS). RESULTS: Expression levels of CC3 and Ki-67 were not associated with any clinicopathological parameter. Patients with non-endometrioid tumours had significantly shorter DFS (P = .001) and OS (P = .001). Low CC3 expression (CC3Low ) was significantly associated with shorter OS (P = .02), but not DFS (P = .13). Multivariate analysis showed that non-endometrioid histology and CC3Low were independent prognostic factors. However, Ki-67 expression was not associated with survival. When endometrioid and non-endometrioid tumours were assessed separately, CC3Low was significantly associated with shorter DFS (P = .002) and OS (P = .002) in patients with non-endometrioid tumours. CONCLUSIONS: Our results suggest that CC3Low in peritoneal cytology samples is a poor prognostic factor in patients with endometrial cancers, especially non-endometrioid tumours. Immunocytochemical analysis of CC3 expression could potentially facilitate identification of patients with high-risk endometrial cancer with PPC.


Subject(s)
Caspase 3/metabolism , Endometrial Neoplasms/metabolism , Peritoneum/metabolism , Adenocarcinoma, Clear Cell/metabolism , Adenocarcinoma, Clear Cell/pathology , Apoptosis/physiology , Carcinoma, Endometrioid/metabolism , Carcinoma, Endometrioid/pathology , Cell Proliferation/physiology , Disease-Free Survival , Endometrial Neoplasms/pathology , Female , Humans , Ki-67 Antigen/metabolism , Middle Aged , Peritoneum/pathology , Prognosis , Retrospective Studies , Risk Factors
14.
Neoplasma ; 64(6): 916-921, 2017.
Article in English | MEDLINE | ID: mdl-28895418

ABSTRACT

Cutaneous angiosarcoma (CA) is extremely rare, and little is known about the biological significance of possible biomarkers for chemotherapeutic agents. Thymidylate synthase (TS) is an attractive target for cancer treatment in various human neoplasms. It remains unclear whether the expression of TS is associated with the clinicopathological features of CA patients. The aim of this study was to elucidate the relationship between TS expression and the clinicopathological significance in CA patients. Fifty-one patients with CA were included in this study. TS expression and Ki-67 labeling index were examined using immunohistochemical analysis. TS was positively expressed in 39% (20/51) of CA patients. No statistically significant prognostic factor was identified as a predictor of overall survival (OS) for all patients by univariate analysis, whereas a significant prognostic variable for progression free survival (PFS) was found to be the clinical stage. In addition, both univariate and multivariate analyses confirmed that positive expression of TS was a significant predictor of worse PFS in CA patients of clinical stage 1. CONCLUSION: Positive TS expression in CA was identified as a significant predictor of worse outcome in patients of clinical stage 1.


Subject(s)
Hemangiosarcoma/enzymology , Skin Neoplasms/enzymology , Thymidylate Synthase/metabolism , Humans , Immunohistochemistry , Prognosis , Progression-Free Survival , Survival Rate
15.
J Hosp Infect ; 96(4): 371-376, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28535969

ABSTRACT

BACKGROUND: Healthcare-associated infections by drug-resistant bacteria affect a patient's prognosis. Infection control activities at medical institutions in Japan are increasingly focused on the threat from these bacteria. AIM: To undertake a full cost analysis that included the costs of consumables and labour required for infection control activities. METHODS: The cost of infection control activities undertaken by the infection control team (ICT) at Nishimino Kosei Hospital in Japan was surveyed from January 2013 to December 2015. The evaluation index of infection control activities used the meticillin-resistant Staphylococcus aureus detection rate. The cost:effectiveness ratio (CER) of each intervention was calculated. FINDINGS: Consumables and labour costs increased over time, as did the ratio of labour cost to total cost over time. However, the CER of interventions was found to have decreased, from ¥164,177 in 2014 to ¥57,989 in 2015. There were increases not only in the amount of consumables, but also in ICT time, suggesting the possibility of improvements in the economic efficiency of infection control. CONCLUSION: Increasing the amount of consumables and the time input of the ICT could help improve the economic efficiency of infection control. Our research suggests the possibility for improvements in the economic efficiency of infection control.


Subject(s)
Cross Infection/prevention & control , Disease Transmission, Infectious/prevention & control , Health Care Costs , Infection Control/economics , Infection Control/methods , Humans , Japan , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Surveys and Questionnaires
16.
Neoplasma ; 64(2): 283-288, 2017.
Article in English | MEDLINE | ID: mdl-28052681

ABSTRACT

L-type amino acid transporter 1 (LAT1) and CD98 are frequently expressed in various human cancers, and closely correlated with tumor aggressiveness and survival. However, little is known about the expression of LAT1 and CD98 in cutaneous angiosarcoma. The aim of this study is to investigate the clinicopathological significance of these markers in the dismal disease. A total of 52 patients with cutaneous angiosarcoma were retrospectively reviewed. Immunohistochemical staining of tumor specimens were evaluated using anti-LAT1, CD98 and Ki-67 antibodies. The rates of high expression for LAT1 and CD98 were 56% (29/52) and 79% (41/52), respectively. The frequency of high expression for CD98 was significantly higher than that for LAT1 (p=0.021). The low expression of CD98 was significantly associated with distant metastasis (p=0.044) and was identified as a significant prognostic predictor by multivariate analysis. The expression level of LAT1 was not significantly correlated with prognosis. The low expression of CD98 is a novel biomarker for predicting poor prognosis in patients with cutaneous angiosarcoma.


Subject(s)
Fusion Regulatory Protein-1/genetics , Hemangiosarcoma/genetics , Large Neutral Amino Acid-Transporter 1/genetics , Biomarkers, Tumor/genetics , Hemangiosarcoma/diagnosis , Humans , Prognosis , Retrospective Studies
17.
J Dent Res ; 95(10): 1191-7, 2016 09.
Article in English | MEDLINE | ID: mdl-27474258

ABSTRACT

It is well known that exposure to maternal separation (MS) in early life causes plastic changes in the nervous system in adulthood, occasionally resulting in ubiquitous chronic pain. However, the pathogenic mechanisms of pain hypersensitivity remain unclear. Here, the authors examined the involvement of corticosterone in orofacial mechanical hypersensitivity induced by MS. To establish a rat model of MS, pups were placed in isolated cages 180 min/d and kept in a temperature-controlled environment at 22 ± 2 °C for 14 d. Mechanical allodynia in the whisker pad skin in adulthood was induced by MS and was significantly suppressed by successive postnatal subcutaneous administration of the glucocorticoid receptor antagonist mifepristone. Corticosterone levels were increased in the serum of MS rats, and successive postnatal administration of subcutaneous corticosterone to naive rats induced mechanical allodynia in the whisker pad skin. The number of P2X3 receptor-immunoreactive (P2X3R-IR) trigeminal ganglion (TG) neurons innervating the whisker pad skin was significantly increased in MS rats and decreased following subcutaneous administration of mifepristone. The number of P2X3R-IR TG neurons innervating the whisker pad skin was also significantly increased following successive postnatal administration of subcutaneous corticosterone in naive rats. Moreover, the mechanical allodynia was suppressed 30 min after administration of the P2X3R antagonist A317491 to the whisker pad skin in MS rats. These findings suggest that the increase in P2X3R-IR TG neurons innervating the whisker pad skin via enhanced neonatal corticosterone signaling by MS plays an important role in orofacial mechanical allodynia in adulthood.


Subject(s)
Facial Pain/pathology , Hyperalgesia/pathology , Maternal Deprivation , Adrenal Cortex Hormones/blood , Adrenal Cortex Hormones/pharmacology , Animals , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Facial Pain/metabolism , Female , Hyperalgesia/metabolism , Male , Mifepristone/pharmacology , Pain Threshold , Rats , Rats, Sprague-Dawley , Receptors, Purinergic P2X3/metabolism , Trigeminal Ganglion/metabolism , Trigeminal Ganglion/pathology , Vibrissae/innervation
18.
Infect Genet Evol ; 43: 245-51, 2016 09.
Article in English | MEDLINE | ID: mdl-27223631

ABSTRACT

Paracoccidioidomycosis (PCM) is a systemic chronic mycosis, endemic in Latin America, especially Brazil, and is the eighth leading cause of death among chronic and recurrent infectious diseases. PCM infection is characterized by the presence of Th1 immune response; the acute form, by a mixed Th2/Th9, while the chronic form is characterized by Th17/Th22 profiles. The occurrence and severity of human PCM may also be associated with genetic factors such as single nucleotide polymorphisms (SNP) on cytokines encoding genes. We investigated the association between these polymorphisms and the different clinical forms of PCM. We included 156 patients with PCM (40 with the acute form, 99 with the chronic multifocal and 17 with the chronic unifocal form) and assayed their DNA samples for IFNG +874 T/A SNP by PCR-ARMS (Amplification Refractory Mutational System), IL12B +1188 A/C SNP on 3' UTR and IL12RB1 641 A/G SNP on exon 7 by PCR-RFLP (Restriction Fragment Length Polymorphism). We found similar genotypic and allelic frequencies of the investigated SNPs among the clinical forms of PCM. Considering male patients, the IL12RB1 641 AA genotype was more frequent in the chronic multifocal form while heterozygosis was in the chronic unifocal form of PCM (p=0.048). Although our data suggest that the AA genotype (IL12RB1) may be associated with the more disseminated chronic disease, more patients of the chronic unifocal PCM group need to be analyzed as well as the secretion patterns of IFN-γ combined with the IL-12Rß1 expression for a better comprehension of this association.


Subject(s)
Host-Pathogen Interactions , Interferon-gamma/genetics , Interleukin-12 Subunit p40/genetics , Paracoccidioidomycosis/genetics , Polymorphism, Single Nucleotide , Receptors, Interleukin-12/genetics , 3' Untranslated Regions , Acute Disease , Adolescent , Adult , Aged , Alleles , Brazil , Child , Chronic Disease , Female , Gene Expression , Gene Frequency , Genotype , Humans , Interferon-gamma/immunology , Interleukin-12 Subunit p40/immunology , Male , Middle Aged , Paracoccidioides/growth & development , Paracoccidioidomycosis/immunology , Paracoccidioidomycosis/microbiology , Paracoccidioidomycosis/pathology , Polymorphism, Restriction Fragment Length , Receptors, Interleukin-12/immunology , Sex Factors
19.
Ann Oncol ; 27(7): 1257-66, 2016 07.
Article in English | MEDLINE | ID: mdl-27052653

ABSTRACT

BACKGROUND: To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma. PATIENTS AND METHODS: A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes. RESULTS: Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P < 0.001). CONCLUSION: Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.


Subject(s)
Carcinoma/pathology , Carcinosarcoma/pathology , Sarcoma/pathology , Uterine Neoplasms/pathology , Adult , Aged , Carcinoma/drug therapy , Carcinoma/epidemiology , Carcinoma/radiotherapy , Carcinosarcoma/drug therapy , Carcinosarcoma/epidemiology , Carcinosarcoma/radiotherapy , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Ifosfamide , Middle Aged , Neoplasm Staging , Radiotherapy, Adjuvant , Retrospective Studies , Sarcoma/drug therapy , Sarcoma/epidemiology , Sarcoma/radiotherapy , Survival Analysis , Treatment Outcome , Uterine Neoplasms/drug therapy , Uterine Neoplasms/epidemiology , Uterine Neoplasms/radiotherapy
20.
Neoplasma ; 63(2): 282-7, 2016.
Article in English | MEDLINE | ID: mdl-26774151

ABSTRACT

Thymidylate synthase (TS) plays an essential role in the pathogenesis and development of cancer, and TS-targeting agents have been widely used against different types of cancers. However, it remains still unclear whether or not TS is expressed in malignant melanoma. We conducted the clinicopathological study to investigate the prognostic significance of TS expression in cutaneous malignant melanoma. Ninety-nine patients with surgically resected cutaneous malignant melanoma were assessed. Tumor sections were stained by immunohistochemistry for TS, Ki-67, and microvessel density (MVD) determined by CD34. TS was positively expressed in 26% (26 out of 99). The expression of TS was significantly associated with T factor, cell proliferation (Ki-67) and MVD (CD34). By Spearman's rank test, TS expression was significantly correlated with Ki67 and CD34. By univariate analysis, ulceration, disease stage, TS, Ki-67 and CD34 had a significant relationship with survival. Multivariate analysis confirmed that TS was an independent prognostic factor for poor prognosis of cutaneous malignant melanoma. The positive expression of TS could be a useful marker for predicting poor prognosis in patients with cutaneous malignant melanoma, and TS-targeting agents may be worth trying for the treatment of this dismal disease.


Subject(s)
Biomarkers, Tumor/metabolism , Melanoma/mortality , Melanoma/pathology , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Thymidylate Synthase/metabolism , Adult , Aged , Aged, 80 and over , Antigens, CD34/metabolism , Carcinogenesis/genetics , Cell Proliferation/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Ki-67 Antigen/metabolism , Male , Melanoma/genetics , Middle Aged , Skin Neoplasms/genetics , Thymidylate Synthase/biosynthesis , Thymidylate Synthase/genetics , Treatment Outcome , Melanoma, Cutaneous Malignant
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