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Biomedical subjects

J Cook

Publications and source records attributed to J Cook.

At least 37 records · Page 2Linked to original sources
PubMed2001

Predicting the reactivity of proteins from their sequence alone: Kazal family of protein inhibitors of serine proteinases.

An additivity-based sequence to reactivity algorithm for the interaction of members of the Kazal family of protein inhibitors with six selected serine proteinases is described. Ten consensus variable contact positions in the inhibitor were identified, and the 19 possible variants at each of these positions were expressed. The free energies of interaction of these variants and the wild type were measured. For an additive system, this data set allows for the calculation of all possible sequences, subject to some restrictions. The algorithm was extensively tested. It is exceptionally fast so that all possible sequences can be predicted. The strongest, the most specific possible, and the least specific inhibitors were designed, and an evolutionary problem was solved.

Algorithms↗
PubMed2001

Five novel RPGR mutations in families with X-linked retinitis pigmentosa.

X-linked forms of retinitis pigmentosa (XLRP) are among the most severe because of their early onset, often leading to significant visual impairment before the fourth decade. RP3, genetically localized at Xp21.1, accounts for 70% of XLRP in different populations. The RPGR (Retinitis Pigmentosa GTPase Regulator) gene that was isolated from the RP3 region is mutated in 20% of North American families with XLRP. From mutation analysis of 27 independent XLRP families, we have identified five novel RPGR mutations in 5 of the families (160delA, 789 A>T, IVS8+1 G>C, 1147insT and 1366 G>A). One of these mutations was detected in a family from Chile. Hum Mutat 17:151, 2001.

Carrier Proteins↗
PubMed2001

Introduction to facial flaps.

The increasing incidence and prevalence of cutaneous neoplasia of the face requiring surgical extirpation demand that the cutaneous surgeon be adept at the repair of a wide spectrum of cutaneous facial defects. By approaching the regional location of a facial wound, the novice or experienced flap surgeon may simplify his or her approach to operative reconstruction. Flap behavior and biomechanics are learned easily with experience, and the informed cutaneous surgeon may obtain superior facial reconstructive results.

Facial Neoplasms↗
PubMed2001

Differential sensitivity to inverse agonists of GABA(A)/benzodiazepine receptors in rats with genetic absence-epilepsy.

A strain of Wistar rats, genetic absence epilepsy rats from Strasbourg (GAERS), was selected and inbred over 40 generations for occurrence of spontaneous spike-wave discharges characteristic of absence seizures, simultaneously with a strain of non-epileptic rats (NER). GAERS demonstrate an excessive sensitivity to antagonists of the GABA(A) receptor. The sensitivity to convulsions induced by various inverse agonists of the GABA(A)/benzodiazepine receptor was compared in GAERS and NERs. The beta-carbolines FG 7142 and DMCM, and the imidazobenzodiazepines RO 19-4603 and the alpha 5-selective RY 024 were several times more convulsant in GAERS than in NERs. The largest differences were found with the non-selective RO 19-4603- and FG 7142. The proconvulsant imidazobenzodiazepine RO 15-4513, binding also to diazepam-insensitive receptors, had low efficacy. The high affinity binding of GABA(A)/BZD receptors with (3H) RO 15-1788 in the brain of naive rats and after administration of FG 7142 did not differ in GAERS and NERs. The data indicate that the hypersensitivity of GAERS to various inverse agonists of the GABA(A)/benzodiazepine receptor involves cortical GABA(A) receptors and is not related to differential activity of a subunit-selective receptor.

Animals↗
PubMed2001

The IAPSRS toolkit: development, utility, and relation to other performance measurement systems. Members of the IAPSRS Research Committee. International Association of Psychological Rehabilitation Services.

The current climate of economic constraint in community-based mental health services has all but required psychosocial rehabilitation (PSR) programs to demonstrate their effectiveness by adopting outcome assessment systems. Agencies of disparate size and varying degrees of sophistication are now responding to mandates to systematically monitor program outcomes. In doing so, however, PSR practitioners and administrators are faced with a bewildering array of competing measures, some of which are impractical, costly, or irrelevant for capturing the outcomes of PSR services (Blankertz & Cook, 1998). To acquaint readers with issues in performance measurement in PSR, this article describes a newly developed outcome measurement system created to document the achievements of service recipients in PSR programs and to monitor progress towards recovery. We discuss principles and logistical issues in performance measurement which are important to PSR agencies and which the Toolkit has been designed to address. Results of the pilot testing of the PSR Toolkit are presented to demonstrate the feasibility of its use, logistical problems in implementation, psychometric properties of the measures, and the Toolkit's sensitivity to change. We discuss next steps in the development of the Toolkit.

Adolescent↗
PubMed2001

Medical education with the Internet: a pilot training programme in reproductive medicine.

Following a detailed information technology survey in the South West Deanery, an Internet educational programme in reproductive medicine was constructed, delivered and assessed. The course followed a problem-based approach using case studies, using an education website and electronic mail (e-mail) to communicate between trainees and trainers. Independent evaluation revealed a high level of satisfaction for both trainees and trainers with an increase in trainees' confidence to deal with patients following the course. This study suggests that the Internet may be used effectively to deliver postgraduate medical education, if the training programme is designed appropriately to computer infrastructure and the computer literacy of the users.

Education, Distance↗
PubMed2001

The effect of resolution, compression, colour depth and display modality on the accuracy of accident and emergency telemedicine.

There are no current recommendations regarding the minimum technical specification for realtime telemedicine consultation in accident and emergency (A and E) practice. We assessed the effect of image resolution, compression, colour depth and display modality on perceived image quality and telediagnosis. Test sets of digitized radiographs and clinical images were subjected to a series of standardized manipulations and the resulting output files were evaluated by an expert panel using image scoring and receiver operating characteristic (ROC) analysis. For telemedicine in A and E work, the minimum technical specification should be regarded as images containing at least 250,000 pixels, compressed at up to JPEG 50 (or GIF for colour images) and displayed on a high-resolution computer monitor. These specifications resulted in average file sizes of 17 kByte for digital images and 9 kByte for radiographs.

Emergency Medicine↗
PubMed2001

Online orthodontic advice: a protocol for a pilot teledentistry system.

A prototype teledentistry service was established that incorporated a PC-based expert system designed to assist in orthodontic cases. It guided the general dental practitioner (GDP) through the assessment of a patient's malocclusion and helped ensure that all relevant clinical observations were made and details recorded. The resulting data file, containing radiographic images and clinical data, was then transferred via the Internet to a dental specialist. The specialist's recommendations were returned by the same route or, where appropriate, a realtime videoconference was conducted. During an eight-month trial, six GDPs referred 158 cases through the teledentistry system; another 24 cases were referred directly to a local consultant. The protocol used during the trial worked satisfactorily. The GDPs found that it was straightforward and covered all aspects of the cases they submitted.

Child↗
PubMed2001

Dentists' opinions of an online orthodontic advice service.

An online teledentistry service was tested for eight months to determine whether it could help to reduce the high level of inappropriate orthodontic referrals to consultants and provide general dental practitioners (GDPs) with quick access to advice that would enable them to tackle a wider range of cases themselves. Six GDPs took part in the trial and were interviewed after it had been running for four months. The most important conclusions from the interviews were that the process of sending cases was quite straightforward, that teledentistry was a good way of getting advice and that it was popular with both patients and their parents. The GDPs enjoyed the experience and felt that there had been significant benefits, especially in educational terms.

Attitude of Health Personnel↗
PubMed2001

Radiation sensitization of mammalian cells by metal chelators.

The cell cycle effects, alteration in radiation response, and inherent cytotoxicity of the metal chelators mimosine, desferrioxamine (DFO), N,N'-bis(o-hydroxybenzyl)-ethylenediamine-N,N'-diacetic acid (HBED), and deferiprone (L1) were studied in exponentially growing Chinese hamster V79 cells. Incubation of cells with 200-1000 microM mimosine for 12 h reduced clonogenic survival to 50-60%, while incubation for 24 h reduced survival further to 0.5%. Mimosine treatment resulted in cell cycle blocks at the G(1)/S-phase border and in S phase. Pulse labeling with 5-bromodeoxyuridine indicated that the S-phase cells ceased to actively replicate DNA after only 2 h of mimosine treatment and were unable to replicate DNA for extended periods. Treatment of V79 cells with 600 microM mimosine for 12 h resulted in radiosensitization, yielding a sensitizer enhancement ratio (SER) of 2.7 +/- 0.3 at the 10% survival level. To study the kinetics of the sensitization, V79 cells were incubated with mimosine for various times up to 12 h and irradiated with a single 10-Gy dose of X rays. It was found that the radiosensitization increased continually up to 8 h (from a 3- to a 100-fold difference in survival) and then reached a plateau after 8 h. Mimosine also equally radiosensitized human lung cancer cells having either a normal or mutated TP53 gene, suggesting a TP53-independent mechanism. To test whether iron binding by mimosine was responsible for the observed radiosensitization, additional experiments were performed using the iron chelators DFO, HBED and L1. V79 cells treated with 500 microM of these agents for 8 h followed by various doses of X rays gave SERs similar to that for mimosine (2.0-2.7). These studies indicate that metal chelators are potent radiosensitizers in V79 and human cells. Importantly, when the DFO was preloaded together with Fe(3+) [Fe(III)-DFO], the radiosensitizing effect was lost. These preliminary findings warrant further studies for the possible application of metal chelators as radiation sensitizers in radiation oncology.

Animals↗
PubMed2001

Differential effects of 15-deoxy-delta(12,14)-prostaglandin J2 and a peroxisome proliferator-activated receptor gamma agonist on macrophage activation.

Prostaglandin J2 metabolite 15-deoxy-delta(12,14)-prostaglandin J2 (15-PGJ2) appears to possess anti-inflammatory properties. Unlike other prostaglandins, it has no known plasma membrane receptor. Its effects have been thought to occur through activation of the nuclear peroxisome proliferator-activated receptor gamma (PPARgamma), but 15-PGJ2 may exhibit effects independent of PPARgamma. We hypothesized that 15-PGJ2 modulates macrophage (Mphi) mediator production by acting on cell signaling proteins upstream of PPARgamma. The effects of 15-PGJ2 on bacterial endotoxin LPS-induced rat peritoneal Mphi mediator production were compared with those of a specific PPARgamma agonist, BRL 49653 (BRL), and to the eicosanoids prostaglandin D2 (PGD2) and cicaprost (CICA, a prostacyclin analogue). 15-PGJ2 inhibited LPS-induced production of NO, TNF-alpha, and thromboxane B2 (TxB2). Equimolar concentrations of PGD2 and CICA significantly inhibited LPS-stimulated TNF-alpha but not NO, and CICA increased TxB2 production. BRL inhibited LPS-induced NO, but augmented LPS-induced TNF-alpha and TxB2. 15-PGJ2 also inhibited degradation of LPS-induced IkappaB alpha and phosphoactivation of ERK 1/2, but BRL had no significant effect on either protein. The cyclopentenone ring 2-cyclopenten-1-one also inhibited LPS-induced ERK 1/2 activation; however, neither 15-PGJ2 nor the cyclopentenone inhibited PMA-induced ERK 1/2 activation. Inhibition of LPS-stimulated mediator production by 15-PGJ2 differed from inhibition by PGD2, CICA, and BRL. The ability of 15-PGJ2 to inhibit LPS-induced Mphi mediator production and cell signaling may occur in part through reactivity of its cyclopentenone ring.

Animals↗
PubMed2001

The case for a one-stop balance centre.

Vertigo, imbalance and dizziness are poorly understood symptoms. This lack of understanding often results in a feeling of therapeutic impotence and frustration. Despair may be felt by the treating physician and hence the patient. This is particularly unfortunate because most patients with imbalance can be helped, often on a single-visit basis.

Ambulatory Care↗
PubMed2000

Case of enantiomer impurity identification by normal-phase chiral high-performance liquid chromatography with optical rotation and mass spectrometric detection.

An impurity produced in the synthesis of compound I is separated and identified as its enantiomer II using normal-phase chiral high-performance liquid chromatography (HPLC) with UV absorbance, optical rotation (OR) and mass spectrometric (MS) detection. The results show that the impurity II and compound I have equal and opposite specific rotations, identical MS spectra and the same MS-MS fragmentation pattern, as required for enantiomers. The procedures presented demonstrate a novel combination of methods for enantiomer identification and characterization that do not require the preparation of individual enantiomer markers or even the racemic mixture, thus reducing the need for additional synthetic work.

Chromatography, High Pressure Liquid↗
PubMed2000

Videoconferencing: what are the benefits for dental practice?

For more than 3 years members of the TeleDent team from Bristol University have been looking at the potential of videoconferencing technology for dentistry. Here they explain what videoconferencing is and how it can help the GDP. They discuss examples of its most promising uses for the profession, which include professional updating and providing diagnostic support at a distance. They describe the equipment that is needed, the different types of system available and give an indication of costs. A suggested procedure for using the technology for remote referrals is outlined. 'Store and forward' techniques are also discussed. These do not involve a live video but involve the sending of static electronic files. This approach is compared with videoconferencing, and the article looks at the question of which will be best suited to the GDP, and for what purposes.

Computer Systems↗
PubMed2000

Three-dimensional whole body imaging of spin probes in mice by time-domain radiofrequency electron paramagnetic resonance.

Imaging of stable paramagnetic spin probes in phantom objects and in vivo was evaluated using a RF time domain EPR spectrometer/imager operating at 300 MHz. Projections were collected using static magnetic field gradients and images were reconstructed using filtered back-projection techniques. Results from phantom objects containing approximately 10(17) spins of stable paramagnetic probes with single narrow EPR spectra provide three-dimensional spatial images with resolution better than 2 mm. When the spin probe was administered to mice, the spin probe accumulation was temporally observed in the thoracic, abdominal, and pelvic regions. A three-dimensional image (from 144 projections) from a live mouse was collected in 5 min. Using fiducial markers, the spin probe accumulation in organs such as liver, kidney, and bladder could be observed. Differences in the oxygen status between liver and kidney were observed from the EPR images from mice administered with spin probe, by treating the time-domain responses with convolution difference approach, prior to image reconstruction. The results from these studies suggest that, with the use of stable paramagnetic spin probes and time-domain RF EPR, it is possible to perform in vivo imaging on animals and also obtain important spatially resolved physiologic information.

Animals↗
PubMed2000

PhRMA perspective on population and individual bioequivalence.

The Food and Drug Administration (FDA) issued a second-draft guidance in August 1999 on the subject of in vivo bioequivalence, which is based on the concepts of individual and population bioequivalence (IBE and PBE, respectively). The intention of this guidance is to replace the 1992 guidance that requires that in vivo bioequivalence be demonstrated by average bioequivalence (ABE). Although the concepts of population and individual bioequivalence are intuitively reasonable, a detailed review of the literature has not uncovered clinical evidence to justify the additional burden to the innovator and generic companies as well as the consumer that the new guidelines would impose. The criteria for bioequivalence described in the draft guidance employ aggregate statistics that combine information about differences in bioavailability between formulation means and differences in bioavailability variation of formulations between and within subjects. The purely technical aspects of the statistical approach are reasonably sound. However, PhRMA believes that important operational issues remain that need to be resolved before any changes to current practice are implemented. PhRMA believes that the ideals of prescribability and switchability are intuitively reasonable, but it is uncertain of the extent to which the proposed guidance can achieve these goals. It is not clear whether the attainment of such goals is necessary in the evaluation of bioequivalence given the role this plays in drug development, and the lack of clinical evidence argues against a pressing need to change current practice. PhRMA is concerned that the trade-off offered by the aggregate criteria may ultimately represent more harm than good to the public interest. PhRMA recommends more rigorous evaluation of methods based on two-way crossover designs before moving to methods that require more complex designs. One such method is identified herein and contains procedures for estimating prescribability and switchability. The possibility of a phase-in or trial period to collect replicate crossover data to further evaluate IBE and PBE and possibly allow market access based on these criteria as they are being evaluated has been proposed. PhRMA believes this is unprecedented and will offer little additional information beyond that which can be obtained by simulation or has already been collected by the FDA. Simulation studies have the advantage of allowing evaluation of the sensitivity of various procedures to represent the data patterns as created within the simulation. Operating characteristics by which proposed criteria can be adequately judged have not yet been defined. The limitations of ABE for highly variable drugs and narrow therapeutic drugs are well appreciated and may be addressed by means other than a wholesale change in the current criteria.

Humans↗