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1.
Clin Exp Immunol ; 203(1): 105-114, 2021 01.
Article in English | MEDLINE | ID: mdl-32909274

ABSTRACT

The aim of this study was to compare the effectiveness of the gene-panel next-generation sequencing (NGS) strategy versus the clinical-based gene Sanger sequencing for the genetic diagnosis of autoinflammatory diseases (AIDs). Secondary goals were to describe the gene and mutation distribution in AID patients and to evaluate the impact of the genetic report on the patient's medical care and treatment. Patients with AID symptoms were enrolled prospectively and randomized to two arms, NGS (n = 99) (32-55 genes) and Sanger sequencing (n = 197) (one to four genes). Genotypes were classified as 'consistent/confirmatory', 'uncertain significance' or 'non-contributory'. The proportion of patients with pathogenic genotypes concordant with the AID phenotype (consistent/confirmatory) was significantly higher with NGS than Sanger sequencing [10 of 99 (10·1%) versus eight of 197 (4·1%)]. MEFV, ADA2 and MVK were the most represented genes with a consistent/confirmed genotype, whereas MEFV, NLRP3, NOD2 and TNFRSF1A were found in the 'uncertain significance' genotypes. Six months after the genetic report was sent, 54 of 128 (42·2%) patients had received effective treatment for their symptoms; 13 of 128 (10·2%) had started treatment after the genetic study. For 59 of 128 (46%) patients, the results had an impact on their overall care, independent of sequencing group and diagnostic conclusion. Targeted NGS improved the diagnosis and global care of patients with AIDs.


Subject(s)
Genotype , Hereditary Autoinflammatory Diseases/diagnosis , Hereditary Autoinflammatory Diseases/genetics , High-Throughput Nucleotide Sequencing , Adult , Female , Humans , Male , Prospective Studies
2.
Diabet Med ; 34(12): 1742-1746, 2017 12.
Article in English | MEDLINE | ID: mdl-29048753

ABSTRACT

AIMS: To assess the prevalence and characteristics of medication errors at hospital admission and discharge in people with Type 1 and Type 2 diabetes, and identify potential risk factors for these errors. METHODS: This prospective observational study included all people with Type 1 (n = 163) and Type 2 diabetes (n = 508) admitted to the Diabetology-Department of the University Hospital of Montpellier, France, between 2013 and 2015. Pharmacists conducted medication reconciliation within 24 h of admission and at hospital discharge. Medication history collected from different sources (patient/family interviews, prescriptions/medical records, contact with community pharmacies/general practitioners/nurses) was compared with admission and discharge prescriptions to detect unintentional discrepancies in medication indicating involuntary medication changes. Medication errors were defined as unintentional medication discrepancies corrected by physicians. Risk factors for medication errors and serious errors (i.e. errors that may cause harm) were assessed using logistic regression. RESULTS: A total of 322 medication errors were identified and were mainly omissions. Prevalence of medication errors in Type 1 and Type 2 diabetes was 21.5% and 22.2% respectively at admission, and 9.0% and 12.2% at discharge. After adjusting for age and number of treatments, people with Type 1 diabetes had nearly a twofold higher odds of having medication errors (odds ratio (OR) 1.72, 95% confidence interval (CI) 1.02-2.94) and serious errors (OR 2.17, 95% CI 1.02-4.76) at admission compared with those with Type 2 diabetes. CONCLUSIONS: Medication reconciliation identified medication errors in one third of individuals. Clinical pharmacists should focus on poly-medicated individuals, but also on other high-risk people, for example, those with Type 1 diabetes.


Subject(s)
Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Medication Errors/statistics & numerical data , Patient Admission/statistics & numerical data , Patient Discharge/statistics & numerical data , Adult , Aged , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Female , France/epidemiology , Humans , Male , Medication Reconciliation/standards , Medication Reconciliation/statistics & numerical data , Middle Aged , Pharmacists/statistics & numerical data , Prevalence , Risk Factors
3.
Eur J Neurol ; 23(11): 1614-1626, 2016 11.
Article in English | MEDLINE | ID: mdl-27435355

ABSTRACT

BACKGROUND AND PURPOSE: The aim of our study was to examine the effect sizes of different cognitive function determinants in middle and early old age. METHODS: Cognitive functions were assessed in 11 711 volunteers (45 to 75 years old), included in the French CONSTANCES cohort between January 2012 and May 2014, using the free and cued selective reminding test (FCSRT), verbal fluency tasks, digit-symbol substitution test (DSST) and trail making test (TMT), parts A and B. The effect sizes of socio-demographic (age, sex, education), lifestyle (alcohol, tobacco, physical activity), cardiovascular (diabetes, blood pressure) and psychological (depressive symptomatology) variables were computed as omega-squared coefficients (ω2 ; part of the variation of a neuropsychological score that is independently explained by a given variable). RESULTS: These sets of variables explained from R2 = 10% (semantic fluency) to R2 = 26% (DSST) of the total variance. In all tests, socio-demographic variables accounted for the greatest part of the explained variance. Age explained from ω2 = 0.5% (semantic fluency) to ω2 = 7.5% (DSST) of the total score variance, gender from ω2 = 5.2% (FCSRT) to a negligible part (semantic fluency or TMT) and education from ω2 = 7.2% (DSST) to ω2 = 1.4% (TMT-A). Behavioral, cardiovascular and psychological variables only slightly influenced the cognitive test results (all ω2 < 0.8%, most ω2 < 0.1%). CONCLUSION: Socio-demographic variables (age, gender and education) are the main variables associated with cognitive performance variations between 45 and 75 years of age in the general population.


Subject(s)
Cognition/physiology , Exercise , Life Style , Age Factors , Aged , Blood Pressure/physiology , Cognition Disorders/psychology , Cohort Studies , Cross-Sectional Studies , Diabetes Mellitus/psychology , Educational Status , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Sex Factors
4.
J Neurol Neurosurg Psychiatry ; 85(4): 363-70, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23840054

ABSTRACT

OBJECTIVE: To investigate the sensitivity of a large set of neuropsychological tests to detect cognitive changes due to prodromal Alzheimer's disease(AD); to compare their metrological properties in order to select a restricted number of these tests for the longitudinal follow-up of subjects with prodromal AD. PARTICIPANTS: 212 patients with mild cognitive impairment were tested at baseline by a standardised neuropsychological battery, which included: the Free and Cued Selective Reminding test (FCSRT), the Benton Visual Retention test, the Deno100, verbal fluency, a serial digit learning test, the double task of Baddeley, the Wechsler Adult Intelligence Scale (WAIS) similarities, the Trail-Making Test and the WAIS digit symbol test. Patients were monitored every 6 months for up to 3 years in order to identify those who converted to AD (retrospectively classified as prodromal AD). Statistical analyses were performed using a nonlinear multivariate mixed model involving a latent process. This model assumes that the psychometric tests are nonlinear transformations of a common latent cognitive process, and it captures the metrological properties of tests. RESULTS: 57 patients converted to AD. The most sensitive tests in the detection of cognitive changes due to prodromal AD were the FCSRT, the semantic verbal fluency and the Deno100. Some tests exhibited a higher sensitivity to cognitive changes for subjects with high levels of cognition, such as the free recall, delayed free recall scores of the FCSRT and the semantic verbal fluency, whereas others showed a higher sensitivity at low levels of cognition, such as the total recall score of the FCSRT. CONCLUSIONS: Tests used for the follow-up of prodromal AD subjects should be chosen among those that actually decline in this stage of the disease and should be selected according to the subject's initial scores.


Subject(s)
Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/psychology , Prodromal Symptoms , Aged , Aged, 80 and over , Alzheimer Disease/complications , Cognitive Dysfunction/complications , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Psychometrics , Retrospective Studies , Sensitivity and Specificity
5.
Epidemiol Psychiatr Sci ; 32: e2, 2023 Jan 10.
Article in English | MEDLINE | ID: mdl-36624696

ABSTRACT

AIMS: People who make medically serious suicide attempts (MSSAs) share a number of features with those who die by suicide, and are at a high risk of suicide themselves. Studies to date have mostly focused on clinical samples of MSSAs. An epidemiological examination at a national level can help to identify risk profiles and pathways of care in this population. METHODS: We explored the French nationwide hospital discharge database (Programme de Médicalisation des Systèmes d'Information, PMSI) to identify any MSSA taking place between 2012 and 2019. Relevant demographic and medical information was collected about the first MSSA of each attempter. Data from 2010 and 2011 were used to verify the absence of prior attempts. RESULTS: First occurrences of MSSAs amounted to 81 959 cases over 8 years, with a mean age of 45.8 years, and 53.6% women. Incidence was higher in women (18.1 v. 17.3 per 1 00 000). The most common suicide method was deliberate self-poisoning (64.9% of cases). In comparison, violent methods associated higher mortality and comorbidity and were more frequent in men. The most common mental disorders were mood disorders (55.6%) and substance use disorders (46.2%). A minority of MSSA survivors were hospitalised in psychiatry (32.5%), mostly women. CONCLUSIONS: MSSAs are frequent and easy to identify. There is a need to reinforce the continuity of psychiatric care for this population given the high risk of subsequent suicide, and the low rates of psychiatric hospitalisation after an MSSA even if violent methods are used. Specific care targeting this population could reduce treatment gaps.


Subject(s)
Patient Discharge , Suicide, Attempted , Male , Humans , Female , Middle Aged , Suicide, Attempted/psychology , Incidence , Aggression , France/epidemiology , Risk Factors
6.
Toxicol Appl Pharmacol ; 263(3): 281-6, 2012 Sep 15.
Article in English | MEDLINE | ID: mdl-22771848

ABSTRACT

Statin use may be limited by muscle side effects. Although incompletely understood to date, their pathophysiology may involve oxidative stress and impairments of mitochondrial function and of muscle Ca(2+) homeostasis. In order to simultaneously assess these mechanisms, 24 male healthy volunteers were randomized to receive either simvastatin for 80 mg daily or placebo for 8 weeks. Blood and urine samples and a stress test were performed at baseline and at follow-up, and mitochondrial respiration and Ca(2+) spark properties were evaluated on a muscle biopsy 4 days before the second stress test. Simvastatin-treated subjects were separated according to their median creatine kinase (CK) increase. Simvastatin treatment induced a significant elevation of aspartate amino transferase (3.38±5.68 vs -1.15±4.32 UI/L, P<0.001) and CK (-24.3±99.1±189.3 vs 48.3 UI/L, P=0.01) and a trend to an elevation of isoprostanes (193±408 vs 12±53 pmol/mmol creatinine, P=0.09) with no global change in mitochondrial respiration, lactate/pyruvate ratio or Ca(2+) sparks. However, among statin-treated subjects, those with the highest CK increase displayed a significantly lower Vmax rotenone succinate and an increase in Ca(2+) spark amplitude vs both subjects with the lowest CK increase and placebo-treated subjects. Moreover, Ca(2+) spark amplitude was positively correlated with treatment-induced CK increase in the whole group (r=0.71, P=0.0045). In conclusion, this study further supports that statin induced muscular toxicity may be related to alterations in mitochondrial respiration and muscle calcium homeostasis independently of underlying disease or concomitant medication.


Subject(s)
Calcium Signaling/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Mitochondria, Muscle/drug effects , Muscle, Skeletal/drug effects , Simvastatin/adverse effects , Adult , Aspartate Aminotransferases/metabolism , Creatine Kinase/metabolism , Dose-Response Relationship, Drug , Double-Blind Method , Follow-Up Studies , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Isoprostanes/metabolism , Male , Mitochondria, Muscle/metabolism , Muscle, Skeletal/metabolism , Rotenone/pharmacology , Simvastatin/administration & dosage , Succinates/metabolism , Young Adult
7.
Osteoporos Int ; 22(12): 3055-66, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21359671

ABSTRACT

UNLABELLED: Peripubertal artistic gymnasts display elevated areal bone mineral density at various bone sites, despite delayed menarche and a high frequency of menstrual disorders, factors that may compromise bone health. The concomitant improvement in femoral bone geometry and strength suggested that this type of physical activity might have favourable clinical impact. INTRODUCTION: The purpose of this study is to evaluate the effect of artistic gymnastics (GYM) on areal bone mineral density (aBMD), femoral bone geometry and bone markers and its relationship with the osteoprotegerin (OPG)/rank-ligand (RANKL) system in peripubertal girls. METHODS: Forty-six girls (age 10-17.2 years) were recruited for this study: 23 elite athletes in the GYM group (training 12-30 h/week, age at start of training 5.3 years) and 23 age-matched (± 6 months; leisure physical activity ≤ 3 h/week) controls (CON). The aBMD at whole body, total proximal femur, lumbar spine, mid-radius and skull was determined using dual-X-ray absorptiometry. Hip structural analysis (HSA software) was applied at the femur to evaluate cross-sectional area (CSA, cm(2)), cross-sectional moment of inertia (CSMI, cm(4)), and the section modulus (Z, cm(3)) and buckling ratio at neck, intertrochanteric region and shaft. Markers of bone turnover and OPG/RANKL levels were also analysed. RESULTS: GYM had higher (5.5-16.4%) non-adjusted aBMD and adjusted aBMD for age, fat-free soft tissue and fat mass at all bone sites, skull excepted and the difference increased with age. In the three femoral regions adjusted for body weight and height, CSA (12.5-18%), CSMI (14-18%), Z (15.5-18.6%) and mean cortical thickness (13.6-21%) were higher in GYM than CON, while the buckling ratio (21-27.1%) was lower. Bone markers decreased with age in both groups and GYM presented higher values than CON only in the postmenarchal period. A similar increase in RANKL with age without OPG variation was observed for both groups. CONCLUSION: GYM is associated not only with an increase in aBMD but also an improvement in bone geometry associated with an increase in bone remodelling. These adaptations seem to be independent of the OPG/RANKL system.


Subject(s)
Bone Density/physiology , Femur/anatomy & histology , Gymnastics/physiology , Osteoprotegerin/metabolism , RANK Ligand/metabolism , Absorptiometry, Photon , Adolescent , Bone Remodeling/physiology , Child , Cross-Sectional Studies , Female , Femur/diagnostic imaging , Humans , Lumbar Vertebrae/diagnostic imaging , Osteoprotegerin/blood , RANK Ligand/blood , Radius/diagnostic imaging
8.
Eur J Neurol ; 17(2): 252-9, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19796284

ABSTRACT

BACKGROUND AND PURPOSE: The objective of this study is to estimate the number of dementia cases expected to occur in France and Europe over the next few decades until 2050. METHODS: Our estimates are based on a model using the European incidence data for dementia by age and sex, the relative mortality risks related to dementia stratified by age classes, and the projections of mortality coefficients in the French and European general population. RESULTS: In France, in 2010, the number of dementia cases should reach 754000, i.e., 1.2% of the general population or 2.8% of the active population. By 2050 this number should be multiplied by 2.4, i.e., 1813000 cases, which will be 2.6% of the total population and 6.2% of the active population. In Europe this number could reach more than 6 millions in 2010 and 14 millions in 2050. The sensitivity analysis performed on French data showed that our projections were robust to the use of alternative data for incidence and relative mortality risk (variation of 5.5% and 6.5%), but very sensitive to hypotheses of evolution of mortality (variation of -22% to 29%). CONCLUSIONS: The approach used in our study, integrating both the dementia incidence and the mortality in the calculations, allowed us to refine the projections and stress the great sensitivity of the demographic hypotheses forecasts on the evolution of life expectancy. The likely increase is particularly important and confirms that French and European health systems must take this into account when making future plans.


Subject(s)
Dementia/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Dementia/economics , Dementia/mortality , Europe/epidemiology , Female , Forecasting , France/epidemiology , Humans , Incidence , Life Expectancy , Male , Middle Aged , Models, Statistical , Risk , Sex Factors , Time Factors , Young Adult
9.
Neuroimage Clin ; 24: 102010, 2019.
Article in English | MEDLINE | ID: mdl-31734532

ABSTRACT

The dynamic connectome perspective states that brain functions arise from the functional integration of distributed and/or partly overlapping networks. Diffuse low-grade gliomas (DLGG) have a slow infiltrating character. Here we addressed whether and how anatomical disconnection following DLGG growth and resection might interfere with functional resting-state connectivity, specifically in relation to picture naming. Thirty-nine native French persons with a left DLGG were included. All underwent awake surgical resection of the tumor using direct brain electrostimulation to preserve critical eloquent regions. The anatomical disconnectivity risk following the DLGG volume and the resection, and the functional connectivity of resting-state fMRI images in relation to picture naming were evaluated prior to and three months after surgery. Resting-state connectivity patterns were compared with nineteen healthy controls. It was demonstrated that picture naming was strongly dependent on the semantic network that emerged from the integration and interaction of regions within multiple resting-state brain networks, in which their specific role could be explained in the light of the broader resting-state network they take part in. It emphasized the importance of a whole brain approach with specific clinical data input, during resting-state analysis in case of lesion. Adaptive plasticity was found in secondary regions, functionally connected to regions close to the tumor and/or cavity, marked by an increased connectivity of the right and left inferior parietal lobule with the left inferior temporal gyrus. In addition, an important role was identified for the superior parietal lobe, connected with the frontal operculum, suggesting functional compensation by means of attentional resources in order to name a picture via recruitment of the frontoparietal attention network.


Subject(s)
Brain Neoplasms , Cerebral Cortex/physiopathology , Connectome , Glioma , Nerve Net/physiopathology , Neuronal Plasticity/physiology , Pattern Recognition, Visual/physiology , Adult , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Brain Neoplasms/surgery , Cerebral Cortex/diagnostic imaging , Female , Glioma/diagnostic imaging , Glioma/pathology , Glioma/surgery , Humans , Male , Middle Aged , Nerve Net/diagnostic imaging , Neurosurgical Procedures
10.
Psychoneuroendocrinology ; 99: 236-242, 2019 01.
Article in English | MEDLINE | ID: mdl-30326381

ABSTRACT

BACKGROUND: Neuroimaging studies suggest that social distress and suicidal vulnerability share common cerebral bases. Moreover, increased peripheral inflammatory activity is involved in both social distress and suicidal behavior. OBJECTIVE: To evaluate, in suicidal and non-suicidal individuals, the association between the activation of specific cerebral regions (anterior cingulate, insula and orbitofrontal cortex) during experimental social exclusion and the baseline blood levels of the pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) and of the anti-inflammatory cytokine interleukin-2 (IL-2). METHODS: In total, 101 euthymic women were recruited: 42 suicide attempters (SA), 40 affective controls (AC), and 19 healthy controls (HC). During functional MRI (fMRI), they performed the Cyberball game, a validated social exclusion task. Blood levels of IL-1ß, IL-6, TNF-α and IL-2 were measured prior to fMRI. The activation of insula, orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC) during the explicit social exclusion (ESE) vs social inclusion (INC) conditions of the Cyberball game was analyzed in function of the baseline cytokine levels. RESULTS: IL-1ß was negatively associated with right OFC activation (p = 0.01) in ESE vs. INC, whereas IL-2 was positively associated with activation of the right ACC (p = 0.02), insula (p = 0.002) and OFC (p = 0.004) in ESE vs. INC. These associations remained significant after controlling for group, indicating that they were independent of the suicidal status. CONCLUSION: Baseline IL-1ß and IL-2 blood levels are differentially associated with cerebral activation involved in the perception of social exclusion, independently of suicidal behavior. Our results may help to better understand the role of basal inflammation in social distress and its link with mood disorder pathophysiology.


Subject(s)
Cytokines/analysis , Suicide, Attempted/psychology , Suicide/psychology , Adult , Cerebral Cortex/physiopathology , Cytokines/blood , Depressive Disorder, Major/psychology , Female , Gyrus Cinguli/physiopathology , Humans , Inflammation/blood , Interleukin-1beta/analysis , Interleukin-1beta/blood , Interleukin-2/analysis , Interleukin-2/blood , Interleukin-6/analysis , Interleukin-6/blood , Magnetic Resonance Imaging/methods , Middle Aged , Prefrontal Cortex/physiopathology , Psychological Distance , Social Behavior , Suicidal Ideation , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/blood
11.
Eur Ann Otorhinolaryngol Head Neck Dis ; 135(2): 105-110, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29289487

ABSTRACT

There is at present no consensus on the treatment of obstructive Eustachian tube dysfunction. In case of failure of well-conducted drug and pressure therapy, some authors recommend balloon dilation; the present study aimed to assess the efficacy and safety of Eustachian tube balloon dilation. MATERIALS AND METHODS: A single-center retrospective study assessed clinical and tubomanometric results of Eustachian tube balloon dilation, complications and satisfaction in a consecutive series managed between June 2012 and February 2015. Indications were based on clinical and paraclinical signs of obstructive tube dysfunction despite well-conducted medical treatment. RESULTS: Forty-five procedures were performed in 38 patients. Improvement in clinical symptoms was assessed as 88%, 80% and 80% at respectively 2 months, 6 months, and>1 year. Improved function on tubomanometry was observed in 81% of cases. The procedure was well tolerated, with a minor complications rate of only 4%. CONCLUSIONS: The present findings for efficacy, tolerance and safety were comparable to those in the literature, despite first-line failure in all patients. Eustachian tube function normalized in about one-third of cases. Despite these encouraging results, true efficacy remains to be confirmed in prospective studies with higher levels of evidence.


Subject(s)
Catheterization/methods , Ear Diseases/physiopathology , Ear Diseases/therapy , Eustachian Tube/physiopathology , Hearing Tests , Adult , Dilatation/instrumentation , Dilatation/methods , Female , Follow-Up Studies , Hearing Tests/methods , Humans , Male , Middle Aged , Patient Satisfaction , Retrospective Studies , Treatment Outcome
12.
J Biochem ; 95(2): 299-309, 1984 Feb.
Article in English | MEDLINE | ID: mdl-6715300

ABSTRACT

Adult rat hepatocytes in primary culture cannot survive more than 2 days in the absence of calf serum. An extract of bovine pituitary gland had a similar effect to calf serum on the survival of hepatocytes, but its specific activity was 70 times that of calf serum. The survival factor was purified from bovine pituitary gland, and obtained in a homogeneous state judging by sodium dodecylsulfate-polyacrylamide gel electrophoresis and high performance liquid chromatography. Its purification was achieved by acid extraction of the pituitary gland, gel filtrations on Sephadex G-75 and Ultrogel AcA 202, ion-exchanger chromatography on CM-cellulose, and then reverse phase high performance liquid chromatography. The purified factor was effective at 10 ng/ml and maximally effective at 100 ng/ml. The overall recovery of its activity was 30%, and the specific activity of the purified factor was 3,100 times that in the acid extract. The molecular weight (Mr 8,000), estimated by Sephadex G-200 filtration, and the strong basic character (pI 10.5) of the purified survival factor suggested that it may be the trypsin inhibitor found in various tissues. Indeed, the amino acid composition of the pure material was identical with that of bovine pancreatic trypsin inhibitor (bPTI). The purified survival factor had the same inhibitory activity on trypsin as commercial bPTI and, conversely, commercial bPTI greatly enhanced survival of rat hepatocytes. Thus, the survival factor in bovine pituitary gland was identified as bPTI.


Subject(s)
Fatty Acid Desaturases/metabolism , Liver/cytology , Pituitary Gland/physiology , Tissue Extracts/pharmacology , Trypsin Inhibitors/isolation & purification , Amino Acids/analysis , Animals , Cattle , Cell Survival/drug effects , Cells, Cultured , Chromatography, Gel , Chromatography, High Pressure Liquid , Fatty Acid Desaturases/analysis , Isoelectric Focusing , Male , Molecular Weight , Rats , Rats, Inbred Strains , Trypsin Inhibitors/physiology
13.
J Chemother ; 11(5): 396-401, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10632387

ABSTRACT

A phase II pilot study was carried out on 30 patients to ascertain the toxicity and efficacy of combination chemotherapy with mitoxantrone, methotrexate, 5-fluorouracil (NMF) in the adjuvant setting for axillary lymph node-positive breast cancer. The NMF regimen was mitoxantrone 10 mg/m2, methotrexate 40 mg/m2, and 5-fluorouracil 600 mg/m2 administered i.v. on day 1, repeated every 3-4 weeks for 6 cycles. The median nadir WBC count was 2,000/microl; grade 4 leukocytopenia occurred only in 1 patient. Nausea and vomiting appeared as grade 0 and 1 severity in 26/30 patients. Alopecia was extremely mild, appeared as grade 0 and 1 in 29/30 patients. The overall and relapse-free survival rates were 67.8% and 68.4% at the 82-month follow-up, respectively. The overall survival rate in premenopausal patients was significantly better than that in postmenopausal patients (P<0.05). NMF is a well-tolerated combination regimen, suitable as adjuvant chemotherapy for node-positive breast cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Adolescent , Adult , Aged , Axilla , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Child , Female , Fluorouracil/administration & dosage , Humans , Lymphatic Metastasis , Methotrexate/administration & dosage , Middle Aged , Mitoxantrone/administration & dosage
14.
Clin Nucl Med ; 16(5): 337-9, 1991 May.
Article in English | MEDLINE | ID: mdl-2054989

ABSTRACT

A 37-year-old man with papillary carcinoma in an ectopic thyroid is presented. Excisional biopsy revealed the cervical mass to be a metastasis from thyroid cancer. X-ray, ultrasonography, and computed tomography, however, failed to identify the primary tumor in the thyroid. Incidental TI-201 uptake was noted in the midline of the anterior neck, and a palpable nodule was discovered in this area. Fine needle aspiration cytology demonstrated Class V papillary adenocarcinoma, and subsequent surgery confirmed a papillary carcinoma in the ectopic thyroid. This case suggests the usefulness of TI-201 scintigraphy for the detection of ectopic thyroid malignancy.


Subject(s)
Adenocarcinoma, Papillary/diagnostic imaging , Choristoma/diagnostic imaging , Head and Neck Neoplasms/diagnostic imaging , Thallium Radioisotopes , Thyroid Gland , Adult , Humans , Male , Radionuclide Imaging
15.
Gan To Kagaku Ryoho ; 19(7): 1071-4, 1992 Jul.
Article in Japanese | MEDLINE | ID: mdl-1626943

ABSTRACT

An advanced gastric cancer with liver metastasis was treated with the combination MMC, Etoposide and UFT. Etoposide was administered orally at 25-50 mg/day to the gastric cancer patient with liver metastasis. In operative findings, there was no liver and lymphoid node metastasis. The gastric tumor diminished in size and changed its characteristics due to the chemotherapy. In 19 months, no liver nor LN metastasis was observed by CT scan. Presently, the patient feels well and receives outpatient treatment.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Gastrectomy , Liver Neoplasms/secondary , Stomach Neoplasms/drug therapy , Administration, Oral , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Administration Schedule , Etoposide/administration & dosage , Humans , Liver Neoplasms/drug therapy , Lymph Node Excision , Male , Mitomycin/administration & dosage , Remission Induction , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Tegafur/administration & dosage , Uracil/administration & dosage
16.
Gan To Kagaku Ryoho ; 24(13): 1947-52, 1997 Oct.
Article in Japanese | MEDLINE | ID: mdl-9350241

ABSTRACT

PyNPase activity, MMPs activity and serum IAP values were measured in tumor tissues from colorectal cancer patients who had been divided into two groups, one given preoperative 5'-DFUR and the controls. PyNPase activity of the preoperative administration group was approximately equivalent to that of the controls. In the control group, correlations were assessed between PyNPase activity and activities of MMP1 and MMP3. To assess the effect of 5'-DFUR on the activity of MMPs, we divided patients into two groups, a high and a low PyNPase activity group. Although there was no correlation with MMPs activity of the preoperative administration group and the control group in the low PyNPase activity group, the activities of MMP1 and MMP9 of the control group were significantly higher in the high PyNPase activity group. Moreover, the serum IAP value of the administration group was significantly lower than that of the control group. These results indicated that PyNPase activity was thus suggested to be somehow related to MMPs activity and serum IAP values.


Subject(s)
Antineoplastic Agents/pharmacology , Colonic Neoplasms/metabolism , Extracellular Matrix/enzymology , Floxuridine/pharmacology , Metalloendopeptidases/metabolism , Neoplasm Proteins/blood , Pentosyltransferases/metabolism , Rectal Neoplasms/metabolism , Adult , Aged , Colonic Neoplasms/drug therapy , Colonic Neoplasms/enzymology , Colonic Neoplasms/pathology , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Pyrimidine Phosphorylases , Rectal Neoplasms/drug therapy , Rectal Neoplasms/enzymology , Rectal Neoplasms/pathology
17.
J Thromb Haemost ; 9(6): 1149-56, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21486425

ABSTRACT

BACKGROUND: Inherited factor (F)VII deficiency is the commonest of the rare bleeding disorders, with a wide set of hemorrhagic features. Other than for the severe clinical forms (for which treatment guidelines are well defined), consistent recommendations regarding perioperative replacement management do not exist for mild and asymptomatic FVII-deficient patients. OBJECTIVES: The present study aimed to evaluate the influence of bleeding history, FVII procoagulant activity levels (FVII:C) and the type of surgical procedure on the management of inherited FVII-deficient patients before surgery. PATIENTS: One hundred and fifty-seven surgical procedures, performed without replacement therapy, in 83 unrelated FVII-deficient patients (median FVII:C=5%, range 0.6%-35%) were analyzed. RESULTS: The overall bleeding rate was 15.3%. We found a significant relationship between previous deep traumatic hematomas and bleeding at surgery, although relationships with previous common epistaxis, easy bruising and menorrhagia were not significant. The receiver-operating characteristic (ROC) curve analysis performed on the first 83 procedures allowed us to define a cut-off value of 7% with a sensitivity of 87% (negative predictive value: 94%). To enhance the sensitivity, and to take into account the potential variation resulting from non-standardized FVII:C measurements, we would suggest applying a threshold of 10%. CONCLUSION: We have proposed recommendations for the perioperative management of FVII-deficient patients based on FVII:C levels, a thorough bleeding history and the type of surgery involved. By applying these recommendations, minor procedures that risk only external or controlled hemorrhage can be performed in asymptomatic or mildly affected adults, even those with FVII:C levels below 10%.


Subject(s)
Blood Loss, Surgical , Factor VII Deficiency , Surgical Procedures, Operative/methods , Female , Hemorrhage/etiology , Humans , Incidence , Male , Perioperative Care , Practice Guidelines as Topic , ROC Curve , Retrospective Studies
18.
AJNR Am J Neuroradiol ; 32(1): 131-6, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20966053

ABSTRACT

BACKGROUND AND PURPOSE: Intracranial stent placement assists in the coiling of wide-neck aneurysms and aids in reconstructing and protecting the parent artery. In this study, we analyze our experience in the use of the Neuroform system. MATERIALS AND METHODS: Records of patients treated with a Neuroform stent from June 2003 to September 2007 were retrieved from a data base for analysis of population characteristics, occurrence of complications, and acute and midterm angiographic results. RESULTS: Sixty-eight patients harboring 76 aneurysms located primarily in the anterior circulation were treated. There were 5 cases (6.6%) of clot formation after deployment (1 with a permanent neurologic deficit), 1 case of perioperative stent displacement with hemorrhage, and 5 cases (6.6%) of transient neurologic deficit due to thromboembolic events. The morbidity-mortality rate at discharge was 2.9%. One patient presented with a delayed in-stent thrombosis, and 3 others, with silent stenosis. Twenty-four aneurysms (31.6%) were completely occluded in the initial embolization. However, a marked increase in the occlusion rate was observed, with 44 of the 68 aneurysms (64.7%) examined at the 18-month follow-up and 26 of the 46 aneurysms (56.5%) examined in the 3-year follow-up presenting with complete occlusion. At the end of the study, a neck remnant was present in 6 aneurysms (13%) and a residual sac, in 7 (15.2%). Mean follow-up time was 25.7 months. CONCLUSIONS: The present series demonstrates the relative safety and feasibility of the Neuroform stent-assisted coiling technique, which seems to provide better results over coiling alone for wide-neck aneurysms. Angiographic results improve with time due to progressive thrombosis of the aneurysm.


Subject(s)
Blood Vessel Prosthesis , Embolization, Therapeutic/instrumentation , Intracranial Aneurysm/surgery , Stents , Aneurysm, Ruptured/surgery , Female , Humans , Intracranial Aneurysm/diagnosis , Longitudinal Studies , Male , Middle Aged , Prosthesis Design , Treatment Outcome
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