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Biomedical subjects

Mark Bennett

Publications and source records attributed to Mark Bennett.

13 recordsLinked to original sources

Topiramate augmentation in treatment-resistant obsessive-compulsive disorder: a retrospective, open-label case series.

Serotonin reuptake inhibitors (SRIs) are considered first-line treatments for obsessive-compulsive disorder (OCD). Many patients achieve some response but remain symptomatic despite an adequate SRI trial. Recent neuroimaging data found abnormally high glutamatergic concentrations in children with OCD. Following selective serotonin reuptake inhibitor (SSRI) treatment, a decrease in OCD symptom severity was associated with a decrease in caudate glutamatergic concentrations. We initiated an investigation of adjunctive topiramate (an anticonvulsant agent with glutamatergic properties) in the treatment of patients with OCD who were partially or nonresponsive to SRI treatment. Sixteen consecutive outpatients with OCD (mean age = 41.1 years; range = 21-58 years), who were partial or nonresponders to SRI monotherapy or SRI combination therapy (antipsychotic, other antidepressant, or benzodiazepines), and had topiramate added over a minimum of 14 weeks, were reviewed. Baseline and endpoint Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I) were evaluated retrospectively. Eleven of 16 patients were responders (68.8%) with a CGI-I score of much improved or very much improved. The mean dose of topiramate was 253.1 +/- 93.9 mg/day. The mean time to response was 9.2 +/- 4.5 weeks. CGI-S scores decreased significantly from initiation of topiramate until 26 weeks, from 6.1 +/- 0.9 to 4.5 +/- 1.3 (P < .001). This case series suggests some preliminary evidence that the addition of topiramate may be useful in treatment-resistant OCD.

Adult↗

Mucin gene expression in nasal polyps.

CONCLUSIONS: A large set of mucin genes is expressed in nasal polyps. The expression pattern is complex and may reflect the wide spectrum of variables involved in polyp formation and progression. Prospective studies including subgroups of nasal polyps and involving substantial numbers of cases in each subgroup will be required to elucidate these variables and to understand how they affect mucus secretion. OBJECTIVE: At present, 15 of the 19 known mucin genes are expressed in the human airways. Nasal polyps might be expected to have a mucin expression pattern comparable to that of the airways. The aim of this study was to investigate mucin expression in nasal polyps. MATERIAL AND METHODS: Nasal polyp samples were obtained from 20 patients during functional endoscopic sinus surgery. Normal (control) sphenoid sinus mucosa was obtained from patients undergoing trans-sphenoid hypophysectomy. The expression of eight mucin genes (MUC1-4, -5AC, -5B, -6 and -7) was studied by in situ hybridization utilizing digoxigenin-labelled oligonucleotide probes. RESULTS: MUC6 and -7 were not expressed in sphenoid sinus mucosa, while all the studied mucin genes were expressed in nasal polyps. Expression patterns varied widely between individual polyps. The predominant epithelial mucin genes were MUC4, -5AC and -3, while MUC5B and -7 were mainly of glandular origin. MUC1, -2 and -6 were weakly expressed. The major alteration in gene expression in nasal polyps was found in the submucosal glands. MUC4 and -5AC represent a major component of both submucosal glands and epithelial cells in nasal polyps.

Biomarkers, Tumor↗

Emerging treatments for child and adolescent social phobia: a review.

Social anxiety disorder, or social phobia (SP), is an anxiety disorder characterized by excessive fear of exposure to situations that involve potential scrutiny by others. SP is a common psychiatric problem in children and adolescents, often presenting with comorbid anxiety and mood disorders. Although the onset of SP is typically in late childhood or early adolescence, most afflicted individuals go undiagnosed for years, not seeking treatment until adulthood. First-line treatments for SP in adults support the use of pharmacotherapy and cognitive behavioral therapy. There is new and emerging data in youths with SP to support the use of similar treatments. This paper will review the clinical characteristics, epidemiology, and treatment of SP in youths. Current investigations using selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors, benzodiazepines, and monoamine oxidase inhibitors in youths will be reviewed. Several studies on the use of cognitive behavioral therapy in youths will also be examined. Practical guidelines for clinicians who treat children and adolescents are also presented.

Adolescent↗

Biophoton imaging: a nondestructive method for assaying R gene responses.

Plant disease resistance (R) proteins of the nucleotide binding-leucine rich repeat class are responsible for pathogen recognition and activation of defense signaling networks leading to the hypersensitive response (HR). Genetically, R-protein signaling appears to be integrated through a limited set of common downstream components. However, the timing of development of visible HR is unique to individual R proteins. By utilizing the phenomena of ultraweak photon emission from leaves undergoing an incompatible interacttion, a powerful nondestructive and facile assay is described to compare timing of defense responses elicited by different R proteins. We demonstrate that ultraweak photon emission, or "biophoton generation," is demonstrated to be associated with hypersensitive cell death. Biophoton emission requires an intact R signaling network and increases in cytosolic calcium and nitric oxide, but elevated reactive oxygen species are not necessary. Importantly, the assay is robust and applicable to a range of incompatible interactions in various plant species. The ability to assay R responses nondestructively in real time and a chosen genetic background makes this technique amenable to subtle genetic dissection of plant defense responses.

Arabidopsis↗

The ecological validity of the "who said what?" technique: an examination of the role of self-involvement, cognitive interference and acquaintanceship.

Questions are raised about the possible ecological invalidity of the traditional "who said what?" (WSW) procedure. Three studies are reported which use a modified, quasi-naturalistic version of the WSW technique, in which rather than being passive recipients of presented information, participants instead play an active role in the production of such information in an interactive context. Data are presented that demonstrate that the social categorization effect typically obtained through the traditional WSW procedure generalizes beyond the circumstances in which it was initially demonstrated. Thus, in Study 1 it was established that social categories (gender, in this case) are cognitively used in real interactions between participants in order to organize information. Moreover, Study 2 demonstrated that the use of categories is accentuated when, as is typical in real world situations, recollections are not made immediately after the perception of the relevant stimuli but following a period of intervening cognitive activity. The findings of Study 3, however, suggest that the WSW technique may not inevitably lead to social categorization effects: typical effects did not appear when participants knew each other well, and therefore saw one another as unique, idiosyncratic individuals, rather than as category members.

Adult↗

IT innovation in histopathology recruitment, training and research.

The introduction of national recruitment and cohort training in histopathology in England has produced significant challenges and highlighted opportunities for development. Innovative information technology solutions have been deployed to facilitate recruitment and enhance education provision and research.

Biomedical Research↗

An evaluation of paroxetine in generalised social anxiety disorder.

It is estimated that social anxiety disorder affects approximately 13.3% individuals within the community at some point in their lifetime and is associated with significant functional impairment. A variety of drug groups have demonstrated efficacy in treating social anxiety disorder, including selective serotonin reuptake inhibitors (SSRIs). Paroxetine is an SSRI approved by the FDA and Health Canada for the treatment of a variety of psychiatric conditions. Paroxetine has been the most studied agent in social anxiety disorder and has been shown to be effective in short-term, fixed- and flexible-dose placebo-controlled trials, as well as in long-term treatment. The pharmacotherapy of social phobia will be reviewed, with a special focus on investigations with paroxetine.

Anxiety Disorders↗

Crossing the digital divide: the contribution of information technology to the professional performance of malaria researchers in Africa.

BACKGROUND: The US National Library of Medicine supports the Multilateral Initiative on Malaria (MIM) through the design, implementation, and operation of the Multilateral Initiative on Malaria Communications Network (MIMCom.) MIMCom makes possible enhanced access to the Internet and to medical literature. OBJECTIVES: The main objectives of the present study were to examine the use of MIMCom supported information technology (IT) by scientists, students, and administrative personnel to facilitate communication, retrieve information, obtain documents, write proposals, and prepare papers for publication; and to determine the contribution of this intervention to their professional performance. METHODS: The authors analyzed the contribution of enhanced Internet connectivity and access to electronic information resources to the performance of malaria research staff and their institutes through a cross-sectional questionnaire survey of 181 respondents at 14 health research centers in Africa. Separate reviews of bandwidth usage, requests for document delivery, and publications in peer reviewed journals support the data of the survey. RESULTS: The MIMCom network makes a positive contribution to the performance of malaria researchers and support staff at the sites reviewed by improving e-mail exchange, access to published literature, and research proposal development and submission. Implications of these findings are discussed. CONCLUSION: By providing full access to the Internet and the resources of the WorldWide Web, MIMCom has been shown to be invaluable to malaria researchers and their institutes in Africa. This access has increased visibility of scientists in their respective institutions and provided opportunities for stronger engagement with the international scientific community.

Access to Information↗

Optimizing treatment in social phobia: a review of treatment resistance.

Over the last 25 years, there has been a rapid expansion of our knowledge base of social phobia (SP). Although there are a number of well-validated treatment modalities, including pharmacotherapy and cognitive-behavioral therapy, significant gaps remain in our ability to achieve full remission in most patients. Despite advances in the neurobiology of SP, the etiology has yet to be determined. Investigations examining potential predictors of response have provided little guidance in selecting an appropriate treatment modality. These gaps in our knowledge have pushed us to examine issues related to treatment resistance. This paper presents a review of the current literature and issues related to treatment-resistant SP, including a discussion of the functional impairment associated with SP, definitions of treatment response and remission, as well as outcome measures that have been used in clinical investigations of SP. In addition, criteria for a standard treatment trial, predictors of treatment response, a review of treatment resistance studies, and potential directions for future research are examined. The most promising strategies to attain remission, will likely involve augmenting selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors with agents such as anticonvulsants, benzodiazepines, and antipsychotics as well as combining pharmacotherapy with cognitive-behavioral therapy. Our current treatment target of simply attaining a response needs to be refocused, so that an asymptomatic state and high end state functioning become the final goal of treatment.

Algorithms↗

Antiepileptic drugs in the treatment of anxiety disorders: role in therapy.

Pharmacotherapy for anxiety disorders is an active area of research. A variety of drug groups have been shown to be effective in treating many of the anxiety disorders, with selective serotonin reuptake inhibitors (SSRIs) being considered first-line agents for virtually all anxiety disorders. There is a clinical need for alternative drug treatments, as many patients do not achieve a complete response and experience significant adverse effects. The successful use of antiepileptic drugs in mood disorders has led clinicians and researchers to investigate their potential efficacy in other psychiatric disorders, particularly in anxiety disorders. There have been a number of investigations conducted in the form of case reports, case series and open-label trials, suggesting the potential usefulness of antiepileptic drug treatment in a variety of anxiety disorders. More reliable evidence for the use of antiepileptic drugs in anxiety disorders can be gleaned from recent placebo-controlled trials. Thus far, the strongest placebo-controlled evidence has demonstrated the efficacy of pregabalin in treating social phobia and generalised anxiety disorder, while smaller or less robust controlled trials have suggested the potential efficacy of gabapentin in social phobia, lamotrigine in post-traumatic stress disorder, and valproic acid in panic disorder. Antiepileptic drugs may have a place in the treatment of anxiety disorders; however, further investigation is warranted to determine in what circumstances they should be used as monotherapy or as augmenting agents in individuals who are partially or non-responsive to conventional therapy.

Anticonvulsants↗

An open trial of topiramate in the treatment of generalized social phobia.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are the current gold standard in the pharmacologic treatment of generalized social phobia. SSRIs are only effective in approximately 50% of individuals with generalized social phobia and can be associated with significant side effects. Based on the successful use of the anticonvulsants gabapentin and pregabalin in treating generalized social phobia, we conducted an open trial examining the efficacy of the glutamatergic and GABAergic anticonvulsant topiramate in the treatment of generalized social phobia. METHOD: Twenty-three adult outpatients with DSM-IV social phobia, generalized type, were entered into a 16-week open trial of topiramate, starting at 25 mg/day, and gradually titrated up to a maximum dose of 400 mg/day. RESULTS: Twelve of 23 patients completed the trial. In the intent-to-treat (ITT) analysis, 11 (47.8%) of 23 were responders by a Clinical Global Impressions Improvement (CGI-I) scale rating of "much" or "very much" improved. The mean drop in the Liebowitz Social Anxiety Scale (LSAS) score for the ITT group was 29.4%. The change in LSAS score from baseline to endpoint was significant for the ITT group (F = 3.44, df = 4,110; p = .01). In the completers group, 9 (75.0%) of 12 were responders by CGI-I at 16 weeks, with a mean drop in LSAS score of 45.1%. The rate of remission in the ITT sample, using a definition of an LSAS score of </= 30, gave a remission rate of 26.1% (6/23). CONCLUSION: This study suggests that topiramate may be effective in the treatment of generalized social phobia. These results also suggest the possibility that the neurotransmitters glutamate and GABA may be involved in the neurobiology of generalized social phobia.

Adult↗

Tying up lions: multilateral initiative on malaria communications: the first chapter of a malaria research network in Africa.

"When spider webs unite, they can tie up a lion" (Ethiopian folk adage). The Multilateral Initiative on Malaria Communications Network (MIMCom) facilitates a new way of doing research in Africa and African scientists' participation in the international scientific community. The MIMCom supports full access to the Internet and the resources of the WorldWide Web at 19 research sites in 11 African countries. Furthermore, the MIMCom project comprises two websites: one includes links to resources, databases, and publications as well as a document delivery service for full text journal articles, and the other is a research agenda specific website with a server for a research network desiring to share raw data. Other important components of MIMCom are training and evaluation components. The MIMCom was conceived in 1997 by African researchers and has been designed, implemented, and overseen by the U.S. National Library of Medicine in collaboration with partners in Africa, the United States, and the United Kingdom. This project demonstrates clearly that it can make a positive difference in the functioning of remote research sites in Africa, in terms of site growth and productivity and in the professional lives of individual researchers. This report reviews the project's background, methods of operation with an emphasis on local needs and priorities, cost effectiveness, and local responsibility; results focusing on a technical network; documentation of the system and two-way exchange of information; the MIMCom website; a network approach to research; and financial sustainability. The report concludes with summaries of evaluations by an independent panel, the Multilateral Initiative on Malaria Secretariat, and the U.S. National Library of Medicine.

Africa↗

SWAP-70-deficient mast cells are impaired in development and IgE-mediated degranulation.

Cross-linking of the high-affinity IgE receptor (FcepsilonRI) on mast cell activates signaling pathways that trigger degranulation and the release of multiple pro-inflammatory mediators. Mature,immature and precursor mast cells are degranulation competent. We show here that the signaling protein SWAP-70 has a function in mast cell biology. While not found in many cell types, we find that apart from B cells, mast cells also express SWAP-70. In activated B cells, SWAP-70 shuttles between cytoplasm and nucleus, but in mast cells it is confined to the cytoplasm. SWAP-70(ko/ko) (double knockout) mice have reduced numbers of mature mast cells, and these are degranulation competent. However, although immature mast cells from SWAP-70(ko/ko) mice respond normally to SCF and IL-3 and have functional granules, their FcepsilonRI-mediated degranulation is inhibited. Thus, in mast cells SWAP-70 plays a role both in establishing the initial competence to degranulate and to develop into mature mast cells.

Animals↗