Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 91
Filter
1.
Cancer Chemother Pharmacol ; 90(4): 335-344, 2022 10.
Article in English | MEDLINE | ID: mdl-36030462

ABSTRACT

BACKGROUND: Notch signaling plays an integral role in development and tissue homeostasis. Inhibition of Notch signaling has been identified as a reasonable target for oncotherapy. Crenigacestat (LY3039478) is a potent Notch inhibitor that decreases Notch signaling and its downstream biologic effects. METHODS: I6F-MC-JJCD was a multicenter, nonrandomized, open-label, phase 1b study with 5 separate, parallel dose escalations in patients with advanced or metastatic cancer from a variety of solid tumors followed by a dose-confirmation phase in pre-specified tumor types. This manuscript reports on 2 of 5 groups. The primary objective was to determine the recommended phase 2 dose of crenigacestat combined with other anticancer agents (gemcitabine/cisplatin or gemcitabine/carboplatin). Secondary objectives included evaluation of safety, tolerability, preliminary efficacy, and pharmacokinetics. RESULTS: Patients (N = 31) received treatment between November 2016 and July 2019. Dose-limiting toxicities occurred in 6 patients. The recommended phase 2 dose for crenigacestat was 50 mg TIW in Part 1 (combined with gemcitabine/cisplatin) and not established in Part 2 (combined with gemcitabine/carboplatin) due to poor tolerability. Patients had at least one treatment-emergent adverse event (TEAE), and most had Grade ≥ 3 TEAEs. Over 50% of the patients experienced gastrointestinal disorders (Grade ≥ 3). No patient had complete response; 5 patients had a partial response. Disease control rates were 62.5% (Part 1) and 60.0% (Part 2). CONCLUSION: This study demonstrated that the Notch inhibitor, crenigacestat, combined with different anticancer agents (gemcitabine, cisplatin, and carboplatin) was poorly tolerated and resulted in disappointing clinical activity in patients with advanced or metastatic solid tumors. CLINICALTRIALS: gov Identification Number: NCT02784795.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Neoplasms, Second Primary , Neoplasms , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Benzazepines , Carboplatin/therapeutic use , Cisplatin/therapeutic use , Deoxycytidine/analogs & derivatives , Humans , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms, Second Primary/drug therapy , Gemcitabine
2.
Rhinology ; 59(2): 114-132, 2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33760909

ABSTRACT

BACKGROUND: Viral respiratory infections are a leading cause of worldwide mortality and exert the potential to cause global socioeconomic crises. However, inexpensive, efficacious, and rapidly deployable strategies to reduce viral transmission are increasingly important in the setting of an ongoing pandemic, though not entirely understood. This article provides a comprehensive review of commonly employed nonpharmacological interventions to interrupt viral spread and provides evidence-based recommendations for their use. METHODOLOGY: A systematic review of three databases was performed. Studies with defined endpoints of subjects receiving one of five interventions (nasal washing, gargling, personal protective equipment (PPE), social distancing, and hand hygiene) were included. An evidence-based review of the highest level of evidence, with recommendations, was created in accordance with a previously described, rigorous, iterative process. RESULTS: Fifty-four primary studies were included. The most commonly studied intervention was hand hygiene, followed by PPE, gargling, saline nasal washing, and social distancing. CONCLUSIONS: Mask use and hand hygiene are strong recommendations for prevention of viral transmission. Donning gloves, gowns, and eye protection are a recommendation in healthcare settings. Saline nasal washing and gargling are options in selected populations. Although an aggregate level of evidence is not provided, the authors recommend social distancing.


Subject(s)
Personal Protective Equipment , Virus Diseases , Humans , Pandemics , Protective Clothing
3.
Invest New Drugs ; 38(2): 402-409, 2020 04.
Article in English | MEDLINE | ID: mdl-30953269

ABSTRACT

Background Deregulated Notch signaling is implicated in multiple cancers. The phase I trial (I6F-MC-JJCA) investigated the safety and anti-tumor activity of crenigacestat (LY3039478), a selective oral Notch inhibitor, in an expansion cohort of patients with adenoid cystic carcinoma (ACC) who received the dose-escalation-recommended phase 2 dose (RP2D), established previously (Massard C, et al., Annals Oncol 2018, 29:1911-17). Methods Patients with advanced or metastatic cancer, measurable disease, ECOG-PS ≤1, and baseline tumor tissue were enrolled. Primary objectives were to identify a safe RP2D, confirm this dose in expansion cohorts, and document anti-tumor activity. Secondary objectives included safety and progression-free survival (PFS). The ACC expansion cohort received the RP2D regimen of 50 mg crenigacestat thrice per week in a 28-day cycle until disease progression or other discontinuation criteria were met. Results Twenty-two patients with ACC were enrolled in the expansion cohort (median age of 60 years). Median treatment duration was 3 cycles with 6 patients remaining on treatment. There were no objective responses; 1 (5%) patient had an unconfirmed partial response. Disease control rate was 73% and 4 patients had stable disease ≥6 months. Median PFS was 5.3 months (95%CI: 2.4-NE)) for the 22 patients; and 7.7 months (95%CI: 4.0-NR) and 2.4 months (95%CI: 1.1-NE) in the subgroup of patients in second-line (n = 7) or ≥ third-line (n = 9), respectively. Frequent treatment-related-adverse events (all grades) included diarrhea, fatigue, vomiting, decreased appetite, dry mouth, and dry skin. There were no new safety signals. Conclusion The crenigacestat RP2D regimen induced manageable toxicity and limited clinical activity, without confirmed responses, in heavily pretreated patients with ACC.


Subject(s)
Antineoplastic Agents/therapeutic use , Benzazepines/therapeutic use , Carcinoma, Adenoid Cystic/drug therapy , Receptor, Notch1/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Antineoplastic Agents/blood , Antineoplastic Agents/pharmacokinetics , Benzazepines/adverse effects , Benzazepines/blood , Benzazepines/pharmacokinetics , Carcinoma, Adenoid Cystic/metabolism , Carcinoma, Adenoid Cystic/mortality , Carcinoma, Adenoid Cystic/pathology , Female , Humans , Male , Middle Aged , Progression-Free Survival , Receptor, Notch1/metabolism , Tumor Burden/drug effects
4.
Ann Oncol ; 29(9): 1911-1917, 2018 09 01.
Article in English | MEDLINE | ID: mdl-30060061

ABSTRACT

Background: Deregulated Notch signaling due to mutation or overexpression of ligands and/or receptors is implicated in various human malignancies. γ-Secretase inhibitors inhibit Notch signaling by preventing cleavage of transmembrane domain of Notch protein. LY3039478 is a novel, potent Notch inhibitor decreases Notch signaling and its downstream biologic effects. In this first-in-human study, we report the safety, pharmacokinetic (PK) profile, pharmacodynamic effects, and antitumor activity of LY3039478 in patients with advanced or metastatic cancer. Methods: This phase I, open-label, multicenter, nonrandomized, and dose-escalation phase study determined and confirmed the recommended phase II dose of LY3039478 (oral dose: 2.5-100 mg, thrice weekly (TIW) on a 28-day cycle). The primary objectives are to determine (part A) and confirm (part B) a recommended phase II dose that may be safely administered to patients with advanced or metastatic cancer, and secondary objectives include evaluation of safety, tolerability, PK parameters, and preliminary antitumor activity of LY3039478. Results: A total of 110 patients were treated with LY3039478 monotherapy between 31 October 2012 and 15 July 2016. Dose-limiting toxicities were thrombocytopenia, colitis, and nausea. Most adverse events were gastrointestinal. The recommended phase II dose was 50 mg TIW, because of its better tolerability compared with 75 mg. The PKs of LY3039478 appeared dose proportional. Pharmacodynamic data indicate an ∼80% inhibition of plasma Aß, and >50% inhibition of Notch-regulated genes hairy and enhancer of split-1, cyclin D1, and Notch-regulated ankyrin repeat at 45-100-mg dose. Clinical activity (tumor necrosis, metabolic response, or tumor shrinkage) was observed in patients with breast cancer, leiomyosarcoma, and adenoid cystic carcinoma. Conclusion: Potent inhibition of Notch signaling by LY3039478 was well tolerated at doses associated with target engagement, and demonstrated evidence of clinical activity in heavily pretreated patients. Further investigation with LY3039478 as monotherapy and in combination with targeted agent or chemotherapy is ongoing. Clinicaltrials.gov ID: NCT01695005.


Subject(s)
Amyloid Precursor Protein Secretases/antagonists & inhibitors , Antineoplastic Agents/administration & dosage , Benzazepines/administration & dosage , Neoplasms/drug therapy , Receptors, Notch/antagonists & inhibitors , Administration, Oral , Adolescent , Adult , Aged , Amyloid Precursor Protein Secretases/blood , Antineoplastic Agents/adverse effects , Benzazepines/adverse effects , Female , Humans , Male , Maximum Tolerated Dose , Middle Aged , Neoplasms/blood , Neoplasms/genetics , Receptors, Notch/genetics , Receptors, Notch/metabolism , Response Evaluation Criteria in Solid Tumors , Young Adult
5.
Am J Transplant ; 17(5): 1278-1285, 2017 May.
Article in English | MEDLINE | ID: mdl-27753206

ABSTRACT

Available literature points to healthcare providers' discomfort with donation after cardiac death (DCD) and their perception of public reluctance toward the procedure. Using a national sample, we report on the communication content of actual DCD and donation after brain death (DBD) approaches by organ procurement organization (OPO) requesters and compare family decision makers' (FDMs') experiences of both modalities. We recruited 1601 FDMs using a validated protocol; 347 (21.7%) were of potential DCD donors. Semistructured telephone interviews yielded FDMs' sociodemographic data, donation attitudes, assessment of approach, final outcomes, and substantiating reasons. Initial analysis consisted of bivariate analyses. Multilevel mixture models compared groups representing authorization outcome and DCD/DBD status. No significant differences in family authorization were found between DCD and DBD cases. Statistically significant associations were found between sociodemographic characteristics and authorization, with white FDMs more likely to authorize DCD or DBD than black FDMs. FDMs of both modalities had similar evaluations of requester skills, topics discussed, satisfaction, and refusal reasons. The findings suggest that the DCD/DBD distinction may not be notable to families. We recommend the use of similar approach strategies and communication skills and the development of education campaigns about the public's acceptance of DCD.


Subject(s)
Brain Death , Death , Health Knowledge, Attitudes, Practice , Tissue Donors , Tissue and Organ Procurement/methods , Adult , Decision Making , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis
6.
Eur J Cancer Care (Engl) ; 25(2): 294-306, 2016 Mar.
Article in English | MEDLINE | ID: mdl-25630765

ABSTRACT

Caregivers play a vital role in caring for people diagnosed with cancer. However, little is understood about caregivers' capacity to find, understand, appraise and use information to improve health outcomes. The study aimed to develop a conceptual model that describes the elements of cancer caregiver health literacy. Six concept mapping workshops were conducted with 13 caregivers, 13 people with cancer and 11 healthcare providers/policymakers. An iterative, mixed methods approach was used to analyse and synthesise workshop data and to generate the conceptual model. Six major themes and 17 subthemes were identified from 279 statements generated by participants during concept mapping workshops. Major themes included: access to information, understanding of information, relationship with healthcare providers, relationship with the care recipient, managing challenges of caregiving and support systems. The study extends conceptualisations of health literacy by identifying factors specific to caregiving within the cancer context. The findings demonstrate that caregiver health literacy is multidimensional, includes a broad range of individual and interpersonal elements, and is influenced by broader healthcare system and community factors. These results provide guidance for the development of: caregiver health literacy measurement tools; strategies for improving health service delivery, and; interventions to improve caregiver health literacy.


Subject(s)
Access to Information , Caregivers , Comprehension , Health Literacy , Health Personnel , Neoplasms/nursing , Professional-Family Relations , Psychosocial Support Systems , Adult , Aged , Female , Humans , Male , Middle Aged , Models, Theoretical , Qualitative Research
7.
Mol Psychiatry ; 19(5): 588-98, 2014 May.
Article in English | MEDLINE | ID: mdl-23835908

ABSTRACT

Converging evidence suggests that females and males show different responses to stress; however, little is known about the mechanism underlying the sexually dimorphic effects of stress. In this study, we found that young female rats exposed to 1 week of repeated restraint stress show no negative effects on temporal order recognition memory (TORM), a cognitive process controlled by the prefrontal cortex (PFC), which was contrary to the impairment in TORM observed in stressed males. Concomitantly, normal glutamatergic transmission and glutamate receptor surface expression in PFC pyramidal neurons were found in repeatedly stressed females, in contrast to the significant reduction seen in stressed males. The detrimental effects of repeated stress on TORM and glutamate receptors were unmasked in stressed females when estrogen receptors were inhibited or knocked down in PFC, and were prevented in stressed males with the administration of estradiol. Blocking aromatase, the enzyme for the biosynthesis of estrogen, revealed the stress-induced glutamatergic deficits and memory impairment in females, and the level of aromatase was significantly higher in the PFC of females than in males. These results suggest that estrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and PFC-dependent cognition, which may underlie the stress resilience of females.


Subject(s)
Cognition/drug effects , Estradiol/pharmacology , Estrogens/pharmacology , Glutamic Acid/metabolism , Stress, Psychological/drug therapy , Stress, Psychological/physiopathology , Animals , Aromatase/metabolism , Aromatase Inhibitors/pharmacology , Cognition/physiology , Female , Male , Memory Disorders/drug therapy , Memory Disorders/physiopathology , Prefrontal Cortex/drug effects , Prefrontal Cortex/physiopathology , Pyramidal Cells/drug effects , Pyramidal Cells/physiopathology , RNA, Messenger/metabolism , Rats, Sprague-Dawley , Receptors, Estrogen/metabolism , Receptors, Glutamate/metabolism , Recognition, Psychology/drug effects , Recognition, Psychology/physiology , Sex Characteristics , Synaptic Transmission/drug effects , Synaptic Transmission/physiology
8.
J Nutr Health Aging ; 17(1): 51-3, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23299380

ABSTRACT

Despite negative topline phase 3 clinical trial results for bapineuzumab and solanezumab in mild to moderate AD, findings from these trials and recent advances suggest renewed optimism for anti-amyloid therapies. Aß immunotherapy has now demonstrated its ability to engage CNS Aß and modify downstream CNS biomarkers in bapineuzumab treated patients, and to show likely cognitive benefits in mild patients treated with solanezumab. The current availability of potent BACE inhibitors provides additional opportunities to test the value of reducing Aß in the clinic. Trial enhancements, such as selecting and enriching for early stage AD, treating participants longer and using more sensitive composite endpoints may further improve our chances of demonstrating clinical efficacy and securing beneficial treatments for patients.


Subject(s)
Alzheimer Disease/diagnosis , Alzheimer Disease/drug therapy , Alzheimer Disease/prevention & control , Amyloid/drug effects , Amyloid/metabolism , Antibodies, Monoclonal, Humanized/therapeutic use , Biomarkers/analysis , Clinical Trials as Topic , Humans , Immunotherapy/methods
9.
Eur J Pain ; 17(3): 382-93, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22893563

ABSTRACT

BACKGROUND: Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor approved for the treatment of diabetic peripheral neuropathic pain (DPNP). The current analyses aimed to identify and evaluate the effect of any significant covariates on DPNP treatment response, via the development of a continuous descriptive Pharmacokinetics/Pharmacodynamics (PK/PD) model for pain score reduction and a proportional odds PK/PD model describing the proportion of patients achieving pain relief. METHODS: A total of 1139 patients received placebo, 20, 60 or 120 mg duloxetine daily for 12 weeks. The primary efficacy measure was 24-h pain scores collected on the 11-point categorical numerical rating scale averaged over a week. PK/PD models were fitted using non-linear mixed-effects models. RESULTS: Baseline pain severity was found to be an important factor in both PK/PD models. Larger drops in pain scores were observed for patients with more severe pain. The proportional odds PK/PD model used an a priori definition for adequate pain relief, which was a decrease in two points from baseline. Simulations showed that approximately 70% of patients in the highest dose groups would obtain pain relief at week 12, although placebo response was relatively high at 40%. The proportion of patients who obtained pain relief was slightly lower in those with mild pain compared to those with more severe pain. CONCLUSIONS: Patients with more severe pain at study entry had larger treatment responses and were more likely to achieve clinically meaningful pain relief with similar amounts of drug, compared to patients with milder pain.


Subject(s)
Analgesics/pharmacokinetics , Analgesics/therapeutic use , Diabetic Neuropathies/drug therapy , Thiophenes/pharmacokinetics , Thiophenes/therapeutic use , Adult , Aged , Aged, 80 and over , Algorithms , Dose-Response Relationship, Drug , Double-Blind Method , Duloxetine Hydrochloride , Female , Humans , Logistic Models , Male , Middle Aged , Models, Statistical , Nonlinear Dynamics , Pain Measurement , Patient Dropouts , Sex Factors , Socioeconomic Factors , Young Adult
10.
Ultraschall Med ; 33(5): 463-8, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23070932

ABSTRACT

PURPOSE: To evaluate the reliability of shear wave ultrasound elastography (SWE) in the neck. MATERIALS AND METHODS: 176 neck lesions (40 thyroid, 56 lymph nodes, 46 salivary, 34 miscellaneous) identified in a routine US clinic underwent SWE by one or two blinded radiologists. For this study, SWE required the operator to acquire three 10 second dynamic colour-coded SWE cineloops per lesion, select one static image per cineloop, and place circular regions-of-interest within the entire lesion and stiffest part to generate 3 SWE measurements per static image. For logistical reasons, one radiologist evaluated all 176 lesions and the other evaluated 58 lesions. Both radiologists also reviewed 27 archived cineloops independently to assess SWE excluding practical technique. Reliability was assessed using intraclass correlation coefficients (ICCs) concordance correlation coefficients (CCCs) and coefficients of repeatability (CORs). RESULTS: Test-retest ICCs for the radiologist evaluating 176 lesions were 0.78 - 0.85 (fair-excellent agreement), CCCs were 0.85 - 0.88 (substantial agreement), and CORs were 14.9 - 36.1 kPa. For both radiologists evaluating 58 lesions, intra-rater and inter-rater ICCs were 0.65 - 0.78 and 0.72 - 0.77 respectively. For SWE excluding practical technique, inter-rater ICCs were 0.97 - 0.98 (excellent agreement). ICCs differed according to tissue, being higher in thyroid lesions than lymph nodes (p < 0.001), and higher in benign than malignant lesions (p values < 0.001). CONCLUSION: Intra- and inter-rater reliability of SWE is fair to excellent according to ICCs. SWE reliability is influenced appreciably by acquisition technique. Nevertheless, CORs for SWE are not negligible. To determine whether these results are acceptable clinically, further research is required to establish SWE stiffness values of normal and pathological tissues in the neck.


Subject(s)
Elasticity Imaging Techniques/methods , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Neck/diagnostic imaging , Otorhinolaryngologic Diseases/diagnostic imaging , Shear Strength/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Lymph Nodes/diagnostic imaging , Male , Middle Aged , Observer Variation , Salivary Gland Diseases/diagnostic imaging , Sensitivity and Specificity , Statistics as Topic , Thyroid Diseases/diagnostic imaging , Young Adult
11.
Mol Psychiatry ; 16(2): 156-70, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20458323

ABSTRACT

Corticosteroid stress hormones have a strong impact on the function of prefrontal cortex (PFC), a central region controlling cognition and emotion, though the underlying mechanisms are elusive. We found that behavioral stressor or short-term corticosterone treatment in vitro induces a delayed and sustained potentiation of the synaptic response and surface expression of N-methyl-D-aspartic acid receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in PFC pyramidal neurons through a mechanism depending on the induction of serum- and glucocorticoid-inducible kinase (SGK) and the activation of Rab4, which mediates receptor recycling between early endosomes and the plasma membrane. Working memory, a key function relying on glutamatergic transmission in PFC, is enhanced in acutely stressed animals through an SGK-dependent mechanism. These results suggest that acute stress, by activating glucocorticoid receptors, increases the trafficking and function of NMDARs and AMPARs through SGK/Rab4 signaling, which leads to the potentiated synaptic transmission, thereby facilitating cognitive processes mediated by the PFC.


Subject(s)
Glutamic Acid/metabolism , Memory, Short-Term/drug effects , Memory, Short-Term/physiology , Prefrontal Cortex/drug effects , Prefrontal Cortex/physiopathology , Synaptic Transmission/drug effects , Animals , Animals, Newborn , Biophysics , Cells, Cultured , Corticosterone/pharmacology , Dose-Response Relationship, Drug , Drug Interactions , Electric Stimulation , Excitatory Amino Acid Agents/pharmacology , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/genetics , Gene Expression Regulation/drug effects , Gene Expression Regulation/genetics , Green Fluorescent Proteins/genetics , Hormone Antagonists/pharmacology , Immediate-Early Proteins/genetics , Immediate-Early Proteins/metabolism , In Vitro Techniques , Long-Term Potentiation/drug effects , Male , Maze Learning/drug effects , Maze Learning/physiology , Mifepristone/pharmacology , Patch-Clamp Techniques/methods , Peptides/pharmacology , Prefrontal Cortex/cytology , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Pyramidal Cells/drug effects , Pyramidal Cells/physiology , RNA, Small Interfering/pharmacology , Rats , Rats, Sprague-Dawley , Receptors, Glutamate/genetics , Receptors, Glutamate/metabolism , Stress, Psychological/pathology , Stress, Psychological/physiopathology , Time Factors , Transfection/methods , rab GTP-Binding Proteins/genetics , rab GTP-Binding Proteins/metabolism
12.
Aliment Pharmacol Ther ; 32(5): 645-54, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20629972

ABSTRACT

BACKGROUND: While there is evidence of ethnic variation in the prevalence of gastro-oesophageal reflux disease (GERD) symptoms, few population-based studies examine GERD symptom prevalence amongst the growing Hispanic minority in the US as well as Asians in the West. AIM: To examine the prevalence, awareness and care patterns for GERD across different ethnic groups. METHODS: A population-based, cross-sectional survey was fielded in English, Chinese and Spanish that assessed self-reported GERD prevalence, awareness and care patterns in four ethnic groups (Caucasian, African American, Asian, Hispanic). RESULTS: A total of 1172 subjects were included for analysis: 34.6% experienced GERD symptoms at least monthly, 26.2% at least weekly and 8.2% at least daily. Statistically significant differences in raw prevalence rates between racial groups were found: 50% of Hispanics experienced heartburn at least monthly, compared with 37% of Caucasians, 31% of African Americans and 20% of Asians (P > 0.0001). Significant differences in knowledge and care-seeking patterns by ethnicity were also observed. CONCLUSIONS: This study confirms the high prevalence of GERD symptoms in the US and introduces Hispanics as the ethnicity with the highest prevalence rate. Asians in the US have higher rates of symptoms than in the Far East. These data demonstrate a need for culturally appropriate education about GERD symptoms and treatment.


Subject(s)
Ethnicity/statistics & numerical data , Gastroesophageal Reflux/ethnology , Gastroesophageal Reflux/therapy , White People/statistics & numerical data , Adolescent , Adult , Black or African American/statistics & numerical data , Aged , Aged, 80 and over , Asian/statistics & numerical data , Female , Gastroesophageal Reflux/epidemiology , Health Knowledge, Attitudes, Practice , Hispanic or Latino/statistics & numerical data , Humans , Male , Middle Aged , Minority Groups , Prevalence , United States/epidemiology , United States/ethnology , Young Adult
13.
Neurology ; 74(9): 714-20, 2010 Mar 02.
Article in English | MEDLINE | ID: mdl-20089937

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of adjunctive topiramate (sprinkle capsules or oral liquid) in reducing daily rates of partial-onset seizures (POS) in infants with refractory POS. METHODS: In this double-blind, placebo-controlled, parallel-group, international study, infants (n = 149) with clinical or EEG evidence of refractory POS were randomly allocated (1:1:1:1) to receive adjunctive topiramate 5, 15, or 25 mg/kg/d or placebo for 20 days. The primary variable was the median percentage reductions in daily POS rate from baseline to final assessment as recorded on a 48-hour video-EEG. RESULTS: Of the 149 infants (mean age 12 months) included in the intent-to-treat analysis set, 130 completed the study. Median percentage reduction from baseline in daily POS rate was not significantly different (p = 0.97) between topiramate 25 mg/kg (20.4%) and placebo (13.1%). Lower doses were not formally tested, but nominal p values for comparisons with placebo were not significant (15-mg/kg/d dose: p = 0.97; 5-mg/kg/d dose: p = 0.91). Treatment-emergent fever, diarrhea, vomiting, anorexia, weight decrease, somnolence, and viral infection occurred more frequently (> or = 10% difference) with topiramate than with placebo. CONCLUSION: In infants aged 1-24 months, topiramate 5, 15, or 25 mg/kg/d was not effective as adjunctive treatment for refractory partial-onset seizures. No new safety concerns associated with topiramate use were noted. CLASSIFICATION OF EVIDENCE: This interventional study provides Class I evidence that topiramate 5, 15, or 25 mg/kg/d compared with placebo does not significantly reduce seizure rates in infants aged 1 month to 2 years with refractory partial-onset seizures.


Subject(s)
Anticonvulsants/therapeutic use , Epilepsies, Partial/drug therapy , Fructose/analogs & derivatives , Seizures/drug therapy , Anticonvulsants/administration & dosage , Anticonvulsants/adverse effects , Brain/drug effects , Brain/physiopathology , Chemotherapy, Adjuvant , Double-Blind Method , Electroencephalography , Epilepsies, Partial/physiopathology , Female , Fructose/administration & dosage , Fructose/adverse effects , Fructose/therapeutic use , Humans , Infant , Male , Seizures/physiopathology , Topiramate , Treatment Outcome , Video Recording
14.
Neurology ; 71(20): 1586-93, 2008 Nov 11.
Article in English | MEDLINE | ID: mdl-19001248

ABSTRACT

OBJECTIVE: To evaluate the efficacy, safety, and tolerability of carisbamate (CRS), an investigational drug, as adjunctive treatment for partial-onset seizures in adults. METHODS: A randomized, double-blind, placebo-controlled, multicenter, dose-ranging study was conducted in 12 countries. Patients counted seizures during an 8-week baseline period, and then, if eligible, entered a double-blind phase consisting of a 4-week dose-titration period (target CRS doses: 100, 300, 800, or 1,600 mg/d or placebo in two divided doses) and a 12-week maintenance period. The primary efficacy variable was percent reduction in partial-onset seizure frequency during the double-blind phase compared with pretreatment baseline. Safety data and responder rates were also assessed. RESULTS: Five hundred thirty-seven patients were randomized, and 82% completed the study. In the intent-to-treat population (n = 533), CRS at doses of > or =300 mg/d (p < or = 0.006) reduced the frequency of partial-onset seizures vs placebo: 6% (placebo) vs 24% (300 mg/d), 21% (800 mg/d), and 29% (1,600 mg/d) for CRS. Adverse events consisted primarily of CNS effects, and led to discontinuation of drug in 8% of the placebo group vs 5% (100 mg/d), 6% (300 mg/d), 12% (800 mg/d), and 19% (1,600 mg/d) of the CRS groups. CONCLUSIONS: Carisbamate at doses of 300, 800, and 1,600 mg/d was effective as adjunctive therapy for reducing the frequency of partial-onset seizures.


Subject(s)
Anticonvulsants/therapeutic use , Carbamates/therapeutic use , Epilepsies, Partial/drug therapy , Adolescent , Adult , Aged , Alanine Transaminase/blood , Body Weight/drug effects , Dose-Response Relationship, Drug , Double-Blind Method , Drug Evaluation , Epilepsies, Partial/blood , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
15.
AJNR Am J Neuroradiol ; 27(8): 1654-7, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16971607

ABSTRACT

Although transcutaneous ultrasound combined with fine-needle aspiration is often used as initial modality for evaluating superficial neck masses, its role in management of deep-seated neck masses is limited. Intraoral ultrasound and guided biopsy helps in obtaining tissue from deep-seated neck masses for an accurate histologic diagnosis, providing useful information in treatment planning. This article discusses the role of intraoral ultrasound and presents 3 cases in which biopsy of deep-seated neck masses under intraoral ultrasound guidance helped in diagnosis and management.


Subject(s)
Biopsy, Needle , Nasopharyngeal Neoplasms/diagnostic imaging , Nasopharyngeal Neoplasms/pathology , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/pathology , Oropharyngeal Neoplasms/diagnostic imaging , Oropharyngeal Neoplasms/pathology , Pharyngeal Neoplasms/diagnostic imaging , Pharyngeal Neoplasms/pathology , Surgery, Computer-Assisted , Ultrasonography, Interventional , Adenoma, Pleomorphic/diagnostic imaging , Adenoma, Pleomorphic/pathology , Adult , Aged, 80 and over , Biopsy, Needle/instrumentation , Carcinoma/diagnostic imaging , Carcinoma/pathology , Diagnosis, Differential , Epstein-Barr Virus Infections/diagnostic imaging , Epstein-Barr Virus Infections/pathology , Female , Humans , Incidental Findings , Lymphatic Metastasis/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Nasopharynx/diagnostic imaging , Nasopharynx/pathology , Nerve Sheath Neoplasms/diagnostic imaging , Nerve Sheath Neoplasms/pathology , Oropharynx/diagnostic imaging , Oropharynx/pathology , Pharynx/diagnostic imaging , Pharynx/pathology , Surgery, Computer-Assisted/instrumentation , Ultrasonography, Interventional/instrumentation
16.
Clin Radiol ; 60(5): 592-8, 2005 May.
Article in English | MEDLINE | ID: mdl-15851048

ABSTRACT

AIM: To evaluate the feasibility of performing in vivo proton magnetic resonance spectroscopy ((1)H-MRS) of cervical lymph nodes, and the clinical usefulness of the technique in the characterization of cervical lymphadenopathy. MATERIALS AND METHODS: Cervical lymphadenopathy was examined in 20 individuals with malignant disease, i.e. 10 with squamous cell carcinoma (SCC), 6 with undifferentiated carcinoma (UDC) and 4 with non-Hodgkin's lymphoma (NHL). Cervical lymphadenopathy was also examined in 4 individuals with benign disease, i.e. 3 with tuberculosis (TB) and 1 with Castleman's disease. A point-resolved spectroscopic sequence with echo times (TE) of 136 and 272 ms and a time-domain spectral fitting procedure were used to estimate peak amplitude of choline (Cho), creatine (Cr) and unsuppressed water. Cho/Cr and Cho/water ratios were measured for each lesion. The mean ratio for each lesion group was obtained and results were compared statistically. RESULTS: At TE of 136 ms, spectra were interpretable in all 24 cases and a Cr peak was identified with post-processing in 15 cases. The Cho/Cr and Cho/water ratios for NHL were 9.1 +/- 5.2 and 1.7 +/- 0.2 x 10(-3), for UDC were 4.4 +/- 0.9 and 1.2 +/- 0.4 x 10(-3), and for SCC were 2.1 +/- 0.6 and 0.5 +/- 0.3 x 10(-3), respectively. Both Cho/Cr and Cho/water ratios for UDC were significantly higher than SCC (p = 0.002 and 0.026, respectively). At TE of 272 ms, spectra were interpretable in 22 of 24 cases and a Cr peak was identified with post-processing in 11 cases. Cho/Cr and Cho/water ratios for NHL were 5.4 and 4.6 +/- 1.4 x 10(-3), for UDC were 4.2 +/- 1.5 and 2.6 +/- 1.0 x 10(-3) and for SCC were 2.5 +/- 1.1 and 1.3 +/- 0.6 x 10(-3), respectively. The Cho/water ratio for UDC was significantly higher than for SCC (p = 0.04). The Cho/Cr ratio for UDC was also higher than for SCC, but this difference was not statistically significant (p = 0.07). Neither Cho nor Cr was detected in the 3 cases of TB. CONCLUSION: In vivo (1)H-MRS is a feasible technique for the evaluation of cervical lymph nodes and it offers potential as a clinical tool in the investigation of cervical lymphadenopathy. However, further studies with larger patient cohorts are needed to validate the findings of this initial report.


Subject(s)
Lymphatic Metastasis/diagnosis , Magnetic Resonance Spectroscopy/methods , Adult , Aged , Aged, 80 and over , Carcinoma/diagnosis , Carcinoma/secondary , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/secondary , Castleman Disease/diagnosis , Diagnosis, Differential , Feasibility Studies , Female , Humans , Lymphoma, Non-Hodgkin/diagnosis , Male , Middle Aged , Neck , Tuberculosis, Lymph Node/diagnosis
17.
Clin Radiol ; 60(2): 141-8, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15664568

ABSTRACT

Thyroglossal duct cyst is the most common congenital cyst in the head and neck, and imaging features have been well documented in the literature. However, there are several practical important points to bear in mind during preoperative imaging, which are often overlooked. This review aims to summarize the imaging findings and emphasize important points for trainees and radiologists, particularly those who may encounter this lesion infrequently.


Subject(s)
Thyroglossal Cyst/diagnosis , Adult , Diagnosis, Differential , Female , Head and Neck Neoplasms/diagnosis , Humans , Male , Middle Aged , Preoperative Care/methods , Referral and Consultation , Thyroglossal Cyst/diagnostic imaging , Tomography, X-Ray Computed/methods , Ultrasonography
18.
Clin Radiol ; 59(11): 967-76, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15488844

ABSTRACT

For patients with primary hyperparathyroidism surgical removal of the hyperfunctioning parathyroid gland is curative. With advances in minimally invasive surgery, accurate pre-operative localization of the hyperfunctioning parathyroid tissue is essential to aid successful surgical treatment. The onus of identifying this hyperfunctioning parathyroid tissue therefore falls on imaging techniques such as high-resolution ultrasound, radionuclide imaging, computed tomography and magnetic resonance imaging. This article is not an exhaustive review, and its main aim is to familiarize the general radiologist, trainee radiologists and clinicians with the basics of various imaging techniques and their roles in practical management of patients with primary hyperparathyroidism.


Subject(s)
Diagnostic Imaging/methods , Hyperparathyroidism/diagnosis , Humans , Magnetic Resonance Imaging/methods , Preoperative Care , Tomography, Emission-Computed, Single-Photon/methods , Tomography, X-Ray Computed/methods
19.
Br J Radiol ; 77(919): 600-6, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15238408

ABSTRACT

Three adult patients with rare vascular lesions in the parotid gland including pseudoaneurysm, arteriovenous fistula and haemangioma are discussed. All patients presented with non-specific unilateral parotid mass. In all cases high-resolution ultrasound and MRI allowed accurate diagnosis and delineation of the extent of lesion. Conventional angiogram was utilized for planning definitive surgical or endovascular treatment.


Subject(s)
Parotid Gland/blood supply , Parotid Neoplasms/diagnosis , Adult , Aged , Aneurysm, False/diagnosis , Angiography, Digital Subtraction , Arteriovenous Fistula/diagnosis , Carotid Artery, External/diagnostic imaging , Female , Hemangioma/diagnosis , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Parotid Gland/diagnostic imaging , Parotid Neoplasms/diagnostic imaging , Ultrasonography, Doppler
20.
Neurology ; 62(9): 1552-7, 2004 May 11.
Article in English | MEDLINE | ID: mdl-15136680

ABSTRACT

OBJECTIVE: To investigate the clinical profile of rofecoxib, a long-acting (approximately 17-hour half-life) selective cyclo-oxygenase-2 inhibitor, for the acute treatment of migraine. METHODS: A randomized, double-blind, placebo-controlled, parallel-group study was conducted. Patients age > or =18 treated a moderate or severe migraine headache with placebo (n = 182), rofecoxib 25 mg (n = 183), or rofecoxib 50 mg (n = 192). The primary efficacy measure was headache relief (mild or no pain) 2 hours after dose. RESULTS: The proportions of patients with migraine headache relief at 2 hours after dose were 34.3% for placebo, 54.0% for rofecoxib 25 mg (p < 0.001 vs placebo), and 56.7% for rofecoxib 50 mg (p < 0.001 vs placebo). Rofecoxib 25 and 50 mg were superior to placebo in providing pain freedom at 2 hours, 24-hour sustained headache relief, and 24-hour sustained pain freedom; in reducing photophobia, phonophobia, nausea (50 mg only), and functional disability at 2 hours after dose; and in improving some quality-of-life scores over 24 hours. More patients on rofecoxib 50 mg reported adverse events (39.6%) than patients on rofecoxib 25 mg (26.8%) or placebo (23.6%) regardless of drug relatedness; however, the incidences of drug-related adverse events were similar between treatment groups. These adverse events were generally mild or moderate in severity. The most commonly reported adverse events were dry mouth, dizziness, somnolence, nausea, dyspepsia, paresthesia, and asthenia, with similar incidences between treatment groups. CONCLUSION: Rofecoxib 25 and 50 mg were effective and generally well tolerated for the acute treatment of migraine attacks.


Subject(s)
Cyclooxygenase Inhibitors/therapeutic use , Migraine Disorders/drug therapy , Acute Disease , Adult , Cyclooxygenase Inhibitors/administration & dosage , Cyclooxygenase Inhibitors/adverse effects , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Female , Health Status , Humans , Lactones/administration & dosage , Lactones/adverse effects , Lactones/therapeutic use , Male , Migraine Disorders/psychology , Pain Measurement/drug effects , Placebos , Quality of Life , Sulfones , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL
...