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1.
Ann Oncol ; 31(4): 525-531, 2020 04.
Article in English | MEDLINE | ID: mdl-32115349

ABSTRACT

BACKGROUND: Preclinical data have shown that proton pump inhibitors (PPI) can modulate the microbiome, and single-arm studies suggested that antibiotics (ATB) may decrease the efficacy of immune checkpoint inhibitors (ICI), but randomized controlled trial data are lacking. This pooled analysis evaluated the effect of ATB and PPI on outcome in patients randomized between ICI and chemotherapy. PATIENTS AND METHODS: This retrospective analysis used pooled data from the phase II POPLAR (NCT01903993) and phase III OAK (NCT02008227) trials, which included 1512 patients with previously treated non-small-cell lung cancer (NSCLC) randomly assigned to receive atezolizumab (nĀ = 757) or docetaxel (nĀ = 755). The main objective of this analysis was to assess the impact of ATB and PPI use on overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 169 (22.3%) patients in the atezolizumab group and 202 (26.8%) in the docetaxel group received ATB, and 234 (30.9%) and 260 (34.4%), respectively, received PPI. Multivariate analysis in all patients revealed that ATB were associated with shorter OS [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.04-1.39], as was PPI (HR 1.26, 95% CI 1.10-1.44). Within the atezolizumab population, OS was significantly shorter in patients who received ATB (8.5 versus 14.1 months, HR 1.32, 95% CI 1.06-1.63, PĀ = 0.01) or PPI (9.6 versus 14.5 months, HR 1.45, 95% CI 1.20-1.75, PĀ =Ā 0.0001). PPI use was associated with shorter PFS in the atezolizumab population (1.9 versus 2.8 months, HR 1.30, 95% CI 1.10-1.53, PĀ = 0.001). There was no association between ATB and PPI use and PFS or OS within the docetaxel population. CONCLUSION: In this unplanned analysis from two randomized trials, data suggest that ATB or PPI use in patients with metastatic NSCLC is associated with poor outcome and may influence the efficacy of ICI.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Anti-Bacterial Agents , Antibodies, Monoclonal, Humanized , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Lung Neoplasms/drug therapy , Proton Pump Inhibitors , Retrospective Studies
2.
Clin Exp Immunol ; 194(2): 166-179, 2018 11.
Article in English | MEDLINE | ID: mdl-30251416

ABSTRACT

Dipeptidyl peptidase 4 (DPP4, CD26) is a serine protease that is expressed constitutively by many haematopoietic and non-haematopoietic tissues. It exists as a membrane-associated protein, as well as in an active, soluble form (herein called sDPP4), present at high concentrations in bodily fluids. Despite the proposed use of sDPP4 as a biomarker for multiple diseases, its cellular sources are not well defined. Here, we report that individuals with congenital lymphocyte immunodeficiency had markedly lower serum concentrations of sDPP4, which were restored upon successful treatment and restoration of lymphocyte haematopoiesis. Using irradiated lymphopenic mice and wild-type to Dpp4-/- reciprocal bone marrow chimeric animals, we found that haematopoietic cells were a major source of circulating sDPP4. Furthermore, activation of human and mouse T lymphocytes resulted in increased sDPP4, providing a mechanistic link between immune system activation and sDPP4 concentration. Finally, we observed that acute viral infection induced a transient increase in sDPP4, which correlated with the expansion of antigen-specific CD8+ T cell responses. Our study demonstrates that sDPP4 concentrations are determined by the frequency and activation state of lymphocyte populations. Insights from these studies will support the use of sDPP4 concentration as a biomarker for inflammatory and infectious diseases.


Subject(s)
Biomarkers/metabolism , Dipeptidyl Peptidase 4/metabolism , Influenza A virus/physiology , Membrane Proteins/metabolism , Orthomyxoviridae Infections/immunology , Severe Combined Immunodeficiency/immunology , T-Lymphocytes/immunology , Animals , Bodily Secretions , Dipeptidyl Peptidase 4/genetics , Disease Models, Animal , Hematopoiesis/genetics , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Solubility , Transplantation Chimera
3.
J Viral Hepat ; 22(6): 524-34, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25382001

ABSTRACT

Chronic infection with HCV is a public health problem with approximately 170 million people infected worldwide. Interferon alpha (IFNα) sensitivity in liver and IL28B genotype has been identified as important determinants of HCV clearance in the setting of pegylated interferon/ribavirin treatment. Herein, we explored IFNα sensitivity in PBMC from 21 healthy donors and 21 HCV-infected patients treated with pegylated interferon/ribavirin and HCV nonstructural protein-3 inhibitors (i.e. telaprevir/boceprevir). We explored phospho-STAT1 level as read-out for IFN signalling pathway activation in PBMC, T cells and monocytes and correlated results with virological response. We found that PBMC from healthy donors are desensitized to IFNα after priming and challenged with IFNα, with a subsequent decrease of phospho-STAT1 and interferon-stimulated genes. Furthermore, we show that CD3+ T cells, but not monocytes, become desensitized after 4 weeks of treatment, with a significant decrease of phospho-STAT1 after ex vivo IFNα stimulation. Finally, we identified baseline phospho-STAT1 level in CD3+ T cells as a potential biomarker of sustained virological response, regardless of the IL28B genotype. In the upcoming costly era of IFN-sparing regimen, baseline IFNα sensitivity could act as biomarker to define cost-effectiveness strategies of treatment by identifying patients who will or will not respond to IFN-based treatments.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/immunology , Interferon-alpha/therapeutic use , T-Lymphocytes/immunology , Aged , Antiviral Agents/pharmacology , Case-Control Studies , Drug Resistance/genetics , Drug Therapy, Combination , Female , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/virology , Humans , Interferon-alpha/pharmacology , Interferons , Interleukins/genetics , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Phosphorylation , Polymorphism, Single Nucleotide , STAT1 Transcription Factor/metabolism , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , Treatment Outcome , Viral Load
4.
Clin Exp Immunol ; 167(1): 137-48, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22132893

ABSTRACT

The ready access to commercially available multiplex assays and the importance of inflammation in disease pathogenesis has resulted in an abundance of studies aimed at identifying surrogate biomarkers for different clinically important questions. Establishing a link between a biomarker and disease pathogenesis, however, is quite complex, and in some instances this complexity is compounded by post-translational modifications and the use of immunoassays that do not always discriminate between the different forms of the same protein. Herein, we provide a detailed description of an assay system that has been established to discriminate the agonist form of CXCL10 from the NH(2) -terminal truncated form of the molecule generated by dipeptidylpeptidase IV (DPP4) cleavage. We demonstrate the utility of this assay system for monitoring agonist and antagonist forms of CXCL10 in culture supernatant, patient plasma and urine samples. Given the important role of CXCL10 in chronic inflammatory diseases and its suggested role as a predictive marker in managing patients with chronic hepatitis C, asthma, atopic dermatitis, transplantation, tuberculosis, kidney injury, cancer and other diseases, we believe that our method will be of general interest to the research and medical community.


Subject(s)
Chemokine CXCL10/analysis , Enzyme-Linked Immunosorbent Assay/methods , Immunoenzyme Techniques/methods , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/immunology , Biomarkers , Body Fluids/chemistry , Carcinoma, Transitional Cell/urine , Chemokine CXCL10/immunology , Culture Media, Conditioned/chemistry , Dipeptidyl Peptidase 4/metabolism , Female , Hepatitis C, Chronic/blood , Humans , Inflammation , Male , Middle Aged , Neoplasm Proteins/urine , Peptide Fragments/analysis , Peptide Fragments/immunology , Protein Isoforms/analysis , Protein Isoforms/immunology , Protein Processing, Post-Translational , Protein Structure, Tertiary , Recombinant Fusion Proteins/analysis , Urinary Bladder Neoplasms/urine
5.
Nat Cell Biol ; 2(12): 899-905, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11146654

ABSTRACT

Integrin receptors are important for the phagocytosis of apoptotic cells. However, little is known about their function in mediating internalization, as previous studies used blocking antibodies for the inhibition of binding. Here we show that the alphavbeta5 receptor mediates both binding and internalization of apoptotic cells. Internalization is dependent upon signalling through the beta5 cytoplasmic tail, and engagement of the alphavbeta5 heterodimer results in recruitment of the p130cas-CrkII-Dock180 molecular complex, which in turn triggers Rac1 activation and phagosome formation. In addition to defining integrin-receptor signalling as critical for the internalization of apoptotic material, our results also constitute the first evidence in human cells that the CED-2-CED-5-CED-10 complex defined in Caenorhabditis elegans is functionally analagous to the CrkII-Dock180-Rac1 molecular complex in mammalian cells. By linking the alphavbeta 5 receptor to this molecular switch, we reveal an evolutionarily conserved signalling pathway that is responsible for the recognition and internalization of apoptotic cells by both professional and non-professional phagocytes.


Subject(s)
Apoptosis/physiology , Integrins/metabolism , Phagocytosis/physiology , Protein Kinases/metabolism , Proteins/metabolism , Proto-Oncogene Proteins , Receptors, Vitronectin , rac GTP-Binding Proteins , rac1 GTP-Binding Protein/metabolism , Base Sequence , Cells, Cultured , DNA Primers/genetics , Dendritic Cells/physiology , HeLa Cells , Humans , Integrins/genetics , Macromolecular Substances , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins c-crk , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Signal Transduction
6.
Nat Med ; 4(11): 1321-4, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9809559

ABSTRACT

Models for immune-mediated tumor regression in mice have defined an essential role for cytotoxic T lymphocytes (CTLs); however, naturally occurring tumor immunity in humans is poorly understood. Patients with paraneoplastic cerebellar degeneration (PCD) provide an opportunity to explore the mechanisms underlying tumor immunity to breast and ovarian cancer. Although tumor immunity and autoimmune neuronal degeneration in PCD correlates with a specific antibody response to the tumor and brain antigen cdr2, this humoral response has not been shown to be pathogenic. Here we present evidence for a specific cellular immune response in PCD patients. We have detected expanded populations of MHC class I-restricted cdr2-specific CTLs in the blood of 3/3 HLA-A2.1+ PCD patients, providing the first description, to our knowledge, of tumor-specific CTLs using primary human cells in a simple recall assay. Cross-presentation of apoptotic cells by dendritic cells also led to a potent CTL response. These results indicate a model whereby immature dendritic cells that engulf apoptotic tumor cells can mature and migrate to draining lymph organs where they could induce a CTL response to tissue-restricted antigens. In PCD, peripheral activation of cdr2-specific CTLs is likely to contribute to the subsequent development of the autoimmune neuronal degeneration.


Subject(s)
Cerebellar Diseases/immunology , Nerve Degeneration/immunology , Paraneoplastic Syndromes/immunology , T-Lymphocytes, Cytotoxic/immunology , Animals , Apoptosis/radiation effects , Breast Neoplasms/immunology , Cells, Cultured , Cytotoxicity, Immunologic , Female , HeLa Cells , Histocompatibility Antigens Class I/immunology , Humans , Immunity, Cellular , Killer Cells, Natural/immunology , Lymphoid Tissue/immunology , Mice , Ovarian Neoplasms/immunology , T-Lymphocyte Subsets/immunology , Ultraviolet Rays
7.
J Exp Med ; 191(3): 423-34, 2000 Feb 07.
Article in English | MEDLINE | ID: mdl-10662788

ABSTRACT

Cell death by necrosis is typically associated with inflammation, in contrast to apoptosis. We have identified additional distinctions between the two types of death that occur at the level of dendritic cells (DCs) and which influence the induction of immunity. DCs must undergo changes termed maturation to act as potent antigen-presenting cells. Here, we investigated whether exposure to apoptotic or necrotic cells affected DC maturation. We found that immature DCs efficiently phagocytose a variety of apoptotic and necrotic tumor cells. However, only exposure to the latter induces maturation. The mature DCs express high levels of the DC-restricted markers CD83 and lysosome-associated membrane glycoprotein (DC-LAMP) and the costimulatory molecules CD40 and CD86. Furthermore, they develop into powerful stimulators of both CD4(+) and CD8(+) T cells. Cross-presentation of antigens to CD8(+) T cells occurs after uptake of apoptotic cells. We demonstrate here that optimal cross-presentation of antigens from tumor cells requires two steps: phagocytosis of apoptotic cells by immature DCs, which provides antigenic peptides for major histocompatibility complex class I and class II presentation, and a maturation signal that is delivered by exposure to necrotic tumor cells, their supernatants, or standard maturation stimuli, e.g., monocyte-conditioned medium. Thus, DCs are able to distinguish two types of tumor cell death, with necrosis providing a control that is critical for the initiation of immunity.


Subject(s)
Apoptosis , Dendritic Cells/physiology , Immune Tolerance/physiology , Neoplasms/immunology , Animals , Antigen-Presenting Cells/immunology , Apoptosis/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cell Line , Culture Media , Dendritic Cells/immunology , Humans , Lymphocyte Activation , Mice , Necrosis , Neoplasms/pathology , Phagocytosis , Phenotype , Signal Transduction , Tumor Cells, Cultured , Ultraviolet Rays
8.
J Exp Med ; 188(7): 1359-68, 1998 Oct 05.
Article in English | MEDLINE | ID: mdl-9763615

ABSTRACT

Dendritic cells, but not macrophages, efficiently phagocytose apoptotic cells and cross-present viral, tumor, and self-antigens to CD8(+) T cells. This in vitro pathway corresponds to the in vivo phenomena of cross-priming and cross-tolerance. Here, we demonstrate that phagocytosis of apoptotic cells is restricted to the immature stage of dendritic cell (DC) development, and that this process is accompanied by the expression of a unique profile of receptors, in particular the alphavbeta5 integrin and CD36. Upon maturation, these receptors and, in turn, the phagocytic capacity of DCs, are downmodulated. Macrophages engulf apoptotic cells more efficiently than DCs, and although they express many receptors that mediate this uptake, they lack the alphavbeta5 integrin. Furthermore, in contrast to DCs, macrophages fail to cross-present antigenic material contained within the engulfed apoptotic cells. Thus, DCs use unique pathways for the phagocytosis, processing, and presentation of antigen derived from apoptotic cells on class I major histocompatibility complex. We suggest that the alphavbeta5 integrin plays a critical role in the trafficking of exogenous antigen by immature DCs in this cross-priming pathway.


Subject(s)
Antigen Presentation/immunology , Apoptosis , CD36 Antigens/metabolism , Dendritic Cells/immunology , Dendritic Cells/metabolism , Integrins/metabolism , Phagocytosis , Receptors, Vitronectin , T-Lymphocytes, Cytotoxic/immunology , Antigens, CD , Cells, Cultured , Histocompatibility Antigens Class I/immunology , Humans , Immunoglobulins/metabolism , Macrophages/metabolism , Membrane Glycoproteins/metabolism , CD83 Antigen
9.
Med Mycol ; 47(3): 327-30, 2009 May.
Article in English | MEDLINE | ID: mdl-19212896

ABSTRACT

In HIV-infected patients, central nervous system (CNS) aspergillosis is rare. Historically, the outcome of such infections has been almost invariably fatal. We report a case involving an AIDS patient with an Aspergillus fumigatus brain abscess who survived for longer than 10 months after surgical drainage and therapy with voriconazole.


Subject(s)
Acquired Immunodeficiency Syndrome/complications , Aspergillus fumigatus/isolation & purification , Neuroaspergillosis/diagnosis , Adult , Antifungal Agents/therapeutic use , Brain/pathology , Head/diagnostic imaging , Humans , Male , Neuroaspergillosis/drug therapy , Neuroaspergillosis/surgery , Pyrimidines/therapeutic use , Radiography , Survival , Time Factors , Treatment Outcome , Triazoles/therapeutic use , Voriconazole
10.
Dement Geriatr Cogn Disord ; 25(2): 109-14, 2008.
Article in English | MEDLINE | ID: mdl-18075249

ABSTRACT

BACKGROUND/AIMS AND METHODS: Perseveration is common in Alzheimer's disease (AD). We document the type and quantitative burden of perseveration as cognitive decline progresses from normal aging (n = 30) through mild AD (n = 20) to moderate AD (n = 20) by administering a semantic verbal fluency task. RESULTS: We found perseveration to increase significantly with increasing severity of AD and different types of perseveration that distinguish the subject groups in a statistically significant manner. Recurrent and continuous perseverations appear early in AD. As the disease progresses in severity into moderate stage, the number of recurrent and continuous perseverations increases, and stuck-in-set perseverations emerge. CONCLUSION: The different types of perseveration are likely to reflect the progressive deterioration of different brain regions in AD.


Subject(s)
Alzheimer Disease/epidemiology , Cognition Disorders/epidemiology , Aged , Aged, 80 and over , Aging/physiology , Brain/physiology , Cognition Disorders/diagnosis , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Semantics , Severity of Illness Index , Verbal Behavior
11.
Antivir Ther ; 12(7): 1041-8, 2007.
Article in English | MEDLINE | ID: mdl-18018762

ABSTRACT

BACKGROUND: Suboptimal improvement in CD4+ T-cell count is not uncommon in HIV-infected patients with suppressed plasma HIV RNA levels, and a decrease in CD4+ T-cell count in patients with suppressed or low-level viraemia has been observed. METHODS: Our objectives were to identify the prevalence of decreasing CD4+ T-cell counts during suppressed or low-level viraemia, to determine the frequency of clinical events during and immediately after such decreases, and to examine for associations with individual variables. A matched case-control study was undertaken using the Duke Infectious Diseases Clinic database (n = 3,949). Cases had at least two consecutive significant decreases in either CD4+ absolute count or CD4+ percentage, while also having plasma HIV RNA levels < 1,000 copies/ml. RESULTS: The prevalence of decreasing CD4+ T-cell counts during suppressed or low-level viraemia was 1.22%. Only three HIV-associated clinical events occurred. The majority of cases had an increase in the CD4+ T-cell count immediately following the study period. The use of either zidovudine or stavudine was weakly associated with decreasing CD4+ T-cell counts in a multivariable analysis, but this association was not present in cases with only a decrease in CD4+ T-cell percentage. CONCLUSIONS: Decreasing CD4+ T-cell counts during suppressed or low-level viraemia are rare, typically transient, and not associated with an increase in HIV-associated clinical events.


Subject(s)
CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , HIV Infections/immunology , HIV Infections/virology , HIV/physiology , Viremia , Adult , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , Case-Control Studies , Female , HIV Infections/drug therapy , Humans , Male , RNA, Viral/blood , Stavudine/therapeutic use , Viral Load , Zidovudine/therapeutic use
12.
Bone Marrow Transplant ; 38(4): 265-73, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16883310

ABSTRACT

The First International Symposium on Photopheresis in Hematopoietic Stem Cell Transplantation was held in Vienna, Austria with an educational grant from Therakos Inc. from 25 May to 27 May 2005. Three general issues were addressed: (1) pathophysiology of graft-versus-host disease (GvHD), (2) induction of immune tolerance and the immunology of phototherapy and (3) current standard treatment and prevention strategies of acute and chronic GvHD and the use of extracorporeal photopheresis (ECP). The objectives of the meeting were to open a dialogue among leading researchers in photobiology, immunology, and hematopoietic stem cell transplantation; foster discussions and suggestions for future studies of the mechanism of action of ECP in acute and chronic GvHD; and promote collaboration between basic scientists and clinicians. As can be seen from the summaries of the individual presentations, important advances have been made in our understanding of GvHD, including the use of photoimmunology interventions and the development of robust model systems. It is our expectation that data from photoimmunology studies can be used to generate hypotheses in animal models that can further define the mechanism of action of ECP and help translate the findings to clinical trials of ECP for the prophylaxis and treatment of both chronic and acute GvHD.


Subject(s)
Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/methods , Photopheresis , Graft vs Host Disease/etiology , Graft vs Host Disease/immunology , Graft vs Host Disease/therapy , Humans , Immune System , Immune Tolerance , Photopheresis/methods
13.
Cancer Res ; 60(8): 2136-9, 2000 Apr 15.
Article in English | MEDLINE | ID: mdl-10786675

ABSTRACT

The paraneoplastic neurological disorders provide perhaps the best known example of naturally occurring tumor immunity in humans. For example, patients with paraneoplastic cerebellar degeneration (PCD) appear to suppress the growth of occult breast or ovarian tumors that express a neuronal antigen termed cdr2. PCD patients harbor cdr2-specific CTLs in their peripheral blood, and these cells are likely mediators of the tumor suppression. Whereas cdr2 therefore appears to be the target of an effective immune response in patients with PCD, the general relevance to cancer patients has been unclear, due in part to reports indicating that cdr2 is not expressed in tumors obtained from neurologically normal patients. We have reexamined this question, and we find that cdr2 is widely expressed in such tumors, indicating that cdr2 is in fact an important tumor antigen in the general population of breast and ovarian cancer patients.


Subject(s)
Antigens, Neoplasm/analysis , Breast Neoplasms/chemistry , Breast Neoplasms/immunology , DNA-Binding Proteins/analysis , Ovarian Neoplasms/chemistry , Ovarian Neoplasms/immunology , Antigens, Neoplasm/immunology , Blotting, Western , DNA-Binding Proteins/immunology , Female , Humans , Immune Sera/immunology , Paraneoplastic Cerebellar Degeneration/immunology , Purkinje Cells , Up-Regulation
14.
Clin Infect Dis ; 40(4): e28-31, 2005 Feb 15.
Article in English | MEDLINE | ID: mdl-15712067

ABSTRACT

We describe a case of coarctation endarteritis in an adult and review the literature pertaining to this condition. Adult coarctation endarteritis is a rare entity but often represents the initial presentation of coarctation. Diagnosis is critically important given the risk of rupture. Cardiovascular magnetic resonance imaging can be helpful in management.


Subject(s)
Aortic Coarctation/diagnostic imaging , Endarteritis/diagnostic imaging , Magnetic Resonance Imaging , Streptococcal Infections/diagnostic imaging , Adolescent , Adult , Aorta/pathology , Aortic Coarctation/diagnosis , Aortic Coarctation/microbiology , Endarteritis/diagnosis , Endarteritis/microbiology , Female , Humans , Male , Radiography , Streptococcal Infections/diagnosis , Streptococcal Infections/microbiology , Viridans Streptococci
15.
Arch Neurol ; 55(11): 1417-9, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9823824

ABSTRACT

Approximately 1 million people have aphasia in the United States today, yet with properly targeted therapy in selected patients effective communication can be restored. Current approaches to treatment of aphasia include psycholinguistic theory-driven therapy, cognitive neurorehabilitation, computer-aided techniques, psychosocial management, and (still on an experimental basis) pharmacotherapy.


Subject(s)
Aphasia/therapy , Forecasting , Neurology/trends , Aphasia/drug therapy , Aphasia/rehabilitation , Cognition Disorders/rehabilitation , Humans , Psycholinguistics , Social Support
16.
Arch Neurol ; 44(12): 1253-5, 1987 Dec.
Article in English | MEDLINE | ID: mdl-3675258

ABSTRACT

We have devised a new approach to the therapy of aphasia. Rather than focus on rehabilitation of linguistic errors, we treat perseveration, which may be an integral component of the aphasic symptoms. In this report we provide key elements of our Treatment of Aphasic Perseveration (TAP) technique, and the successful use of this method with three aphasic patients.


Subject(s)
Aphasia/therapy , Humans , Male , Middle Aged , Neuropsychological Tests
17.
Arch Neurol ; 33(6): 453-4, 1976 Jun.
Article in English | MEDLINE | ID: mdl-938268

ABSTRACT

In a prospective study we evaluated the relationship of level of consciousness to hemispheric side of lesion following acute cerebrovascular injury. Fifty-seven percent of patients with left hemispheric lesions had initial impairment of consciousness, in contrast to 25% with right-sided damage.


Subject(s)
Cerebrovascular Disorders/physiopathology , Consciousness , Dominance, Cerebral , Cerebrovascular Disorders/cerebrospinal fluid , Functional Laterality , Humans
18.
Arch Neurol ; 42(2): 127-9, 1985 Feb.
Article in English | MEDLINE | ID: mdl-2579625

ABSTRACT

Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in the sixth, 13th, and 20th milliliters of CSF in patients with dementia of the Alzheimer's type (DAT) and Parkinson's disease (PD), and in an aliquot of CSF in controls. In patients with PD there was a positive correlation between 5-HT and 5-HIAA levels in the 20th milliliter of CSF, while in patients with DAT there was a negative correlation of these levels in this CSF fraction. In patients with the senile form of DAT the 5-HIAA levels in the 20th milliliter of CSF were higher than in patients with PD. These results indicate differential involvement of the serotoninergic system in DAT and PD, and may lead to the development of a chemical marker for DAT.


Subject(s)
Alzheimer Disease/cerebrospinal fluid , Dementia/cerebrospinal fluid , Hydroxyindoleacetic Acid/cerebrospinal fluid , Parkinson Disease/cerebrospinal fluid , Serotonin/cerebrospinal fluid , Aged , Humans
19.
Arch Neurol ; 47(2): 129-32, 1990 Feb.
Article in English | MEDLINE | ID: mdl-2302084

ABSTRACT

To characterize cognitive impairments following multiple subcortical lacunar infarcts (lacunes), we prospectively compared the neuropsychological performance of 11 subjects with multiple lacunes with 11 medical control subjects matched for age and education who had no clinical or computed tomographic evidence of central nervous system disease. Subjects with multiple subcortical lacunes displayed neuropsychological signs of frontal system dysfunction, even though only 27% met the criteria for clinical diagnosis of dementia. They exhibited significant deficits in shifting mental set, response inhibition, and executive function. In addition, they were more often rated apathetic on a behavior-rating scale. We propose a continuum of cognitive impairments in lacunar states, ranging from frontal systems impairment to dementia.


Subject(s)
Cerebral Infarction/physiopathology , Frontal Lobe/physiopathology , Cerebral Infarction/complications , Dementia/complications , Dementia/diagnosis , Humans , Neuropsychological Tests , Prospective Studies
20.
Arch Neurol ; 41(9): 935-41, 1984 Sep.
Article in English | MEDLINE | ID: mdl-6477229

ABSTRACT

We examined the relationship of disease laterality to neuropsychological and neurochemical features in patients with idiopathic Parkinson's disease (PD). We tested patients with PD, patients with Alzheimer's type of senile dementia, and a control group neuropsychologically, and we determined their CSF levels of homovanillic acid, 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindolacetic acid, serotonin, and acetylcholinesterase. The patients with PD were divided into two groups depending on the side of the body with greater disease involvement. Both parkinsonian groups, those more affected on the left (group L) and those more affected on the right (group R), were otherwise similar in all other clinical and historical features. Group L patients showed greater neuropsychological impairments than group R patients. Group L also had significantly higher CSF levels of homovanillic acid and acetylcholinesterase than group R. These findings of neuropsychological and neurochemical differences between groups L and R suggest functional or anatomic asymmetries of dopaminergic systems in the CNS.


Subject(s)
Alzheimer Disease/psychology , Dementia/psychology , Parkinson Disease/psychology , Acetylcholinesterase/cerebrospinal fluid , Aged , Alzheimer Disease/cerebrospinal fluid , Cognition , Dementia/cerebrospinal fluid , Functional Laterality , Homovanillic Acid/cerebrospinal fluid , Humans , Language , Middle Aged , Parkinson Disease/cerebrospinal fluid , Wechsler Scales
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