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Biomedical subjects

Robert Bennett

Publications and source records attributed to Robert Bennett.

14 recordsLinked to original sources
PubMed2006

Design, synthesis, and progress toward optimization of potent small molecule antagonists of CC chemokine receptor 8 (CCR8).

Activation of CCR8 by its ligand CCL1 may play an important role in diseases such as asthma, multiple sclerosis, and cancer. The study of small molecule CCR8 antagonists will help establish the validation of these hypotheses. We report the design, synthesis, and progress toward optimization of potent small molecule CCR8 antagonists identified from a high-throughput screen. These analogues exhibit good potency in binding and chemotaxis assays, show good selectivity versus the hERG channel, and have good eADME (early absorption, distribution, metabolism, and excretion) profiles.

Amination↗
PubMed2006

Cognitive behavioral therapy for fibromyalgia.

Cognitive behavioral therapy (CBT) techniques offer short-term, goal-oriented psychotherapy. In this respect, it differs from classical psychoanalysis in emphasizing changes in thought patterns and behaviors rather than providing 'deep insight'. Importantly, the beneficial effects of CBT can be achieved in 10-20 sessions, compared with the many years required for classical psychoanalysis. Although CBT is often done on a one-to-one basis, it also lends itself to a group therapeutic setting. CBT was initially used in the treatment of mood disorders, but its use has subsequently been expanded to include various other medical conditions, including chronic pain states. Over the past 18 years, several chronic pain treatment programs have used CBT techniques in the management of fibromyalgia. In this review, the results from 13 programs using CBT, alone or in combination with other treatment modalities, are analyzed. In most studies, CBT provided worthwhile improvements in pain-related behavior, self-efficacy, coping strategies and overall physical function. Sustained improvements in pain were most evident when individualized CBT was used to treat patients with juvenile fibromyalgia. The current data indicate that CBT, as a single treatment modality, does not offer any distinct advantage over well-planned group programs of education or exercise, or both. Its role in the management of fibromyalgia patients needs further research.

Clinical Trials as Topic↗
PubMed2006

Compatibility of interventional x-ray and magnetic resonance imaging: feasibility of a closed bore XMR (CBXMR) system.

A next-generation interventional guidance system is proposed that will enable intraprocedural access to both x-ray and magnetic resonance imaging (MRI) modalities. This closed bore XMR (CBXMR) system is comprised of a conventional radiographic rotating anode x-ray tube and a direct conversion flat panel detector on a rotating gantry positioned adjacent to the bore of a 1.5 T MRI. To assess the feasibility of such a system, we have investigated the degree of compatibility between the x-ray components and the MRI. For /-->B(ext)/ < 200 G the effect on the radiographic tube motor was negligible regardless of the orientation of -->B(ext) with respect to the motor axis of rotation--the frequency of anode rotation remained within 6% of the 3400 rpm frequency measured at 0 G. For /-->B(ext)/ >2400 G the anode slowed down to below 2400 rpm at all orientations. At intermediate B(ext), the frequency of rotation varied between 2400 and 3200 rpm, showing a strong dependence on orientation, with -->B(ext) perpendicular to the tube axis having a much stronger effect on the rotation frequency than -->B(ext) parallel to the tube axis. In contrast to the effect of -->B(ext) on the induction motor, parallel -->B(ext) had a stronger detrimental effect on the cathode-anode electron beam, whose path was at 16 degrees to the tube axis, than the perpendicular -->B(ext). Parallel -->B(ext) of several hundred Gauss had a defocusing effect on the x-ray focal spot. -->B(ext) perpendicular to the electron beam shifted the beam without significant defocusing. We have determined that the direct conversion flat panel detector (FPD) technology is not intrinsically sensitive to -->B(ext), and that the modifications required to make the proposed FPDs MRI compatible are minimal. The homogeneity of the MRI signal in the normal field of view was not significantly degraded by the presence of these x-ray components in the vicinity of the MRI bore entrance.

Equipment Design↗
PubMed2005

Growth hormone in musculoskeletal pain states.

Growth hormone is essential for normal linear growth and the attainment of an adult mature height. It also plays an important role in cartilage growth and the attainment of normal bone mass. There is only one rheumatic disorder, namely acromegaly, in which abnormalities of growth hormone production play a major etiologic role. However, there is increasing appreciation that suboptimal growth hormone secretion, leading to a state of adult growth hormone deficiency, may occur in the setting of chronic inflammatory disease, chronic corticosteroid use, and fibromyalgia. Therefore, the evaluation and effective management of growth hormone oversecretion and undersecretion is relevant to practicing rheumatologists.

Acromegaly↗
PubMed2005

Fibromyalgia: present to future.

There has been a dramatic increase in our understanding of fibromyalgia throughout the past 14 years since the publication of the 1990 American College of Rheumatology classification criteria. Before 1990, and for most of the 20th century, fibromyalgia was considered to be predominantly a muscle disorder; now the critical abnormality is described as "central sensitization." However, central sensitization has to have an initial genesis and nociceptive stimuli from painful foci in muscle are increasingly recognized as being relevant to the development of fibromyalgia. Clinicians also recognize an association between the initiation of fibromyalgia and chronic psychologic stressors and inflammatory disorders. It has been more difficult to understand how two such apparently diverse events could affect central pain physiology. However, some clues are emerging from the role of diverse stimuli in activating glial cells and the role of disordered cytokine networks. Some predictions about future developments in fibromyalgia are ventured based on the current state of knowledge.

Fibromyalgia↗
PubMed2004

ORFDB: an information resource linking scientific content to a high-quality Open Reading Frame (ORF) collection.

The ORFDB (http://orf.invitrogen.com/) represents an ongoing effort at Invitrogen Corporation to integrate relevant scientific data with an evolving collection of human and mouse Open Reading Frame (ORF) clones (Ultimate ORF Clones). The ORFDB serves as a central data warehouse enabling researchers to search the ORF collection through its web portal ORFBrowser, allowing researchers to find the Ultimate ORF clones by blast, keyword, GenBank accession, gene symbol, clone ID, Unigene ID, LocusLink ID or through functional relationships by browsing the collection via the Gene Ontology (GO) Browser. As of October 2003, the ORFDB contains 6200 human and 2870 mouse Ultimate ORF clones. All Ultimate ORF clones have been fully sequenced with high quality, and are matched to public reference protein sequences. In addition, the cloned ORFs have been extensively annotated across six categories: Gene, ORF, Clone Format, Protein, SNP and Genomic links, with the information assembled in a format termed the ORFCard. The ORFCard represents an information repository that documents the sequence quality, alignment with respect to public protein sequences, and the latest publicly available information associated with each human and mouse gene represented in the collection.

Animals↗
PubMed2004

Fibromyalgia: present to future.

There has been a dramatic increase in our understanding of fibromyalgia throughout the past 14 years since the publication of the 1990 American College of Rheumatology classification criteria. Before 1990, and for most of the 20th century, fibromyalgia was considered to be predominantly a muscle disorder; now the critical abnormality is described as "central sensitization." However, central sensitization has to have an initial genesis and nociceptive stimuli from painful foci in muscle are increasingly recognized as being relevant to the development of fibromyalgia. Clinicians also recognize an association between the initiation of fibromyalgia and chronic psychologic stressors and inflammatory disorders. It has been more difficult to understand how two such apparently diverse events could affect central pain physiology. However, some clues are emerging from the role of diverse stimuli in activating glial cells and the role of disordered cytokine networks. Some predictions about future developments in fibromyalgia are ventured based on the current state of knowledge.

Fibromyalgia↗
PubMed2004

Growth hormone in musculoskeletal pain states.

Growth hormone is essential for normal linear growth and the attainment of an adult mature height. It also plays an important role in cartilage growth and the attainment of normal bone mass. There is only one rheumatic disorder, namely acromegaly, in which abnormalities of growth hormone production play a major etiologic role. However, there is increasing appreciation that suboptimal growth hormone secretion, leading to a state of adult growth hormone deficiency, may occur in the setting of chronic inflammatory disease, chronic corticosteroid use, and fibromyalgia. Therefore, the evaluation and effective management of growth hormone oversecretion and undersecretion is relevant to practicing rheumatologists.

Acromegaly↗
PubMed2004

A database for Chinese outpatients with rheumatic diseases.

Although several databases have been developed in rheumatology aimed at profiling the morbidity pattern of rheumatic diseases, or to capture the detailed clinical and outcome information of patients with a specific rheumatic disease, there is no database in China, as yet, for capturing visit-related health information of all outpatients with rheumatic diseases. In this project, a relational database was developed for the rheumatic outpatient clinic of Peking Union Medical College Hospital (PUMCH). The primary goal of this database is to collect and organize visit-related information of outpatients with rheumatic diseases to meet information needs of clinical research, health care continuity and teaching of rheumatic diseases. The implementation of this database can improve health services, medical records management and clinical research of outpatients with rheumatic disease at PUMCH.

China↗
PubMed2003

Raman spectroscopy, a potential tool for the objective identification and classification of neoplasia in Barrett's oesophagus.

Histopathology remains the gold standard technique for the diagnosis of intraepithelial neoplasia (dysplasia) in Barrett's oesophagus, but it is highly subjective and relies on blind biopsy targeting. The aim of this study was to evaluate Raman spectroscopy, a rapid, non-invasive, molecular, specific analytical technique, for the objective identification and classification of Barrett's neoplasia in vitro. A secondary objective was to demonstrate the need for a rigorous gold standard in the development of new diagnostic techniques. Forty-four patients with a mean age of 69 years (range 34-89 years) undergoing surveillance for Barrett's oesophagus were included in the study. Three consultant pathologists independently assessed snap-frozen oesophageal biopsy specimens. Raman spectra were measured on 87 histopathologically homogeneous samples. Spectral classification models were developed using multivariate analysis for the prediction of pathology. Histopathology and Raman classification results were compared. Raman spectral prediction with a consensus pathology classification model gave sensitivities between 73% and 100% and specificities of 90-100%. A high level of agreement (kappa = 0.89) was demonstrated between the three-subset biopsy targeting model and consensus pathology opinion. This compares favourably with the agreement measured between an independent pathologist and the consensus pathology opinion for the same spectra (kappa = 0.76). Raman spectroscopy appears to provide a highly sensitive and specific technique for the identification and classification of neoplasia in Barrett's oesophagus.

Adult↗
PubMed2002

Impaired growth hormone secretion in fibromyalgia patients: evidence for augmented hypothalamic somatostatin tone.

OBJECTIVE: To determine whether female fibromyalgia (FM) patients exhibit a normal growth hormone (GH) response to an acute exercise stressor, and to assess the importance of somatostatin tone in the generation of this GH response. METHODS: Twenty female FM patients were compared with 10 healthy female controls. All subjects exercised to volitional exhaustion on a treadmill. A standard metabolic cart was used to monitor pulse, blood pressure, electrocardiography, oxygen uptake, carbon dioxide output, anaerobic threshold, and maximal workload. Blood was drawn for GH and cortisol measurements 1 hour before exercise, immediately before exercise, immediately after exercise, and 1 hour after exercise. One month later, testing that was exactly similar was performed, except all subjects were given pyridostigmine bromide (Mestinon; 30 mg orally) 1 hour before exercise. RESULTS: Compared with controls, FM patients failed to exhibit a GH or cortisol response to acute exercise (P = 0.003). After administration of pyridostigmine, 1 hour before exercise, the GH levels of FM patients increased 8-fold (P = 0.001), to a value comparable with that of controls. Pyridostigmine did not increase the cortisol response to exercise in FM patients. Pyridostigmine alone did not stimulate GH secretion in FM patients, nor did it improve exercise-induced GH secretion in controls. FM patients with normal insulin-like growth factor 1 (IGF-1) levels had an impaired GH response to exercise. CONCLUSION: Three new findings are reported: 1) FM patients have a reduced GH response to exercise, 2) pyridostigmine reverses this impaired response, and 3) defective GH secretion in FM can occur in patients with normal IGF-1 levels. Because pyridostigmine is known to reduce somatostatin tone, it is surmised that the defective GH response to exercise in FM patients probably results from increased levels of somatostatin, a hypothalamic hormone that inhibits GH secretion.

Adult↗