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Biomedical subjects

I M Marks

Publications and source records attributed to I M Marks.

At least 19 recordsLinked to original sources
PubMed2006

Computer-aided vs. tutor-delivered teaching of exposure therapy for phobia/panic: randomized controlled trial with pre-registration nursing students.

BACKGROUND: Exposure therapy is effective for phobic anxiety disorders (specific phobias, agoraphobia, social phobia) and panic disorder. Despite their high prevalence in the community, sufferers often get no treatment or if they do, it is usually after a long delay. This is largely due to the scarcity of healthcare professionals trained in exposure therapy, which is due, in part, to the high cost of training. Traditional teaching methods employed are labour intensive, being based mainly on role-play in small groups with feedback and coaching from experienced trainers. In an attempt to increase knowledge and skills in exposure therapy, there is now some interest in providing relevant teaching as part of pre-registration nurse education. Computers have been developed to teach terminology and simulate clinical scenarios for health professionals, and offer a potentially cost effective alternative to traditional teaching methods. OBJECTIVE: To test whether student nurses would learn about exposure therapy for phobia/panic as well by computer-aided self-instruction as by face-to-face teaching, and to compare the individual and combined effects of two educational methods, traditional face-to-face teaching comprising a presentation with discussion and questions/answers by a specialist cognitive behaviour nurse therapist, and a computer-aided self-instructional programme based on a self-help programme for patients with phobia/panic called FearFighter, on students' knowledge, skills and satisfaction. DESIGN: Randomised controlled trial, with a crossover, completed in 2 consecutive days over a period of 4h per day. PARTICIPANTS: Ninety-two mental health pre-registration nursing students, of mixed gender, age and ethnic origin, with no previous training in cognitive behaviour therapy studying at one UK university. RESULTS: The two teaching methods led to similar improvements in knowledge and skills, and to similar satisfaction, when used alone. Using them in tandem conferred no added benefit. Computer-aided self-instruction was more efficient as it saved teacher preparation and delivery time, and needed no specialist tutor. CONCLUSION: Computer-aided self-instruction saved almost all preparation time and delivery effort for the expert teacher. When added to past results in medical students, the present results in nurses justify the use of computer-aided self-instruction for learning about exposure therapy and phobia/panic and of research into its value for other areas of health education.

Analysis of Variance↗
PubMed2004

Saving clinicians' time by delegating routine aspects of therapy to a computer: a randomized controlled trial in phobia/panic disorder.

BACKGROUND: The demand for time-consuming psychotherapy of phobia/panic exceeds the supply of trained therapists. Delegating routine therapy aspects to a computer might ease this problem. METHOD: Ninety-three out-patients with phobia or panic disorder were randomized in a 2: 2 : 1 ratio to have self-exposure therapy guided either mainly by a stand-alone computer system (FearFighter) or entirely face-to-face by a clinician, or to have mainly computer-guided self-relaxation as a placebo. Both computer groups (FearFighter and relaxation) had brief back-up advice from a clinician. Primary outcome measures were self- and blind-assessor ratings of Main Problem and Goals, and Global Phobia. RESULTS: Drop-outs occurred significantly more often in the two self-exposure groups (43% if mainly computer-guided, 24% if entirely clinician-guided) than with self-relaxation (6%); the difference between the two self-exposure groups was not significant. Even with all drop-outs included, the mainly computer-guided exposure group and the relaxation group had 73% less clinician time per patient than did the entirely clinician-guided exposure group. The two self-exposure groups had comparable improvement and satisfaction at post-treatment and at 1-month follow-up, while relaxation was ineffective. Mean improvement on the primary outcome measures (self- and assessor-rated) was 46% computer, 49% clinician, 9% relaxation at post-treatment (week 10) and 58% computer, 53% clinician and -4% relaxation at 1-month follow-up (week 14). Mean effect sizes on the primary outcome measures were 2.9 computer, 3.5 clinician and 0.5 relaxation at post-treatment; and 3.7 computer, 3.5 clinician and 0.5 relaxation at 1-month follow-up. The assessor did not rate patients at follow-up. CONCLUSIONS: Despite its (non-significantly) higher dropout rate, self-exposure therapy for panic/ phobia cut clinician time per patient by 73% without losing efficacy when guided mainly by a computer rather than entirely by a clinician. The finding needs confirmation at a follow-up that is longer and includes a blind assessor. Self-relaxation had the highest rate of completers but was ineffective.

Analysis of Variance↗
PubMed2002

Beliefs, sense of control and treatment outcome in post-traumatic stress disorder.

BACKGROUND: Few studies have shown that maladaptive beliefs relate to treatment outcome. METHOD: In a randomized controlled study, 87 patients with post-traumatic stress disorder (PTSD) had exposure therapy alone or cognitive restructuring alone, or both combined, or relaxation. Independent blind assessors assessed patients at pre-, mid- and post-treatment and at follow-up; at those times patients rated cognitive, behavioural and emotional aspects of their disorder. RESULTS: Baseline beliefs about mistrust, helplessness, meaninglessness and unjustness of the world related to baseline PTSD symptoms but did not predict treatment outcome, though improvement in certain beliefs correlated with more symptom improvement. Several 'key' beliefs changed after, and none before, symptoms improved. At post-treatment, sense of control and attribution of gains to personal efforts predicted maintenance of gains at follow-up. CONCLUSIONS: Baseline beliefs and improvement in beliefs did not predict outcome. Post-treatment sense of control/internal attribution predicted maintenance of gains at follow-up. How much sense of control is produced by or causes improvement deserves testing.

Adolescent↗
PubMed2001

Two-year follow-up after a randomised controlled trial of self- and clinician-accompanied exposure for phobia/panic disorders.

BACKGROUND: Long-term follow-up has rarely been reported after self-exposure therapy for phobias. AIMS: Completion of such a follow-up. METHOD: Two-year follow-up was achieved in 68 (85%) of 80 patients with phobias who had completed a previous 14-week randomised controlled trial comparing therapist-accompanied self-exposure, self-exposure or self-relaxation. Measures were self-reported ratings of symptoms, satisfaction and use of other treatment. RESULTS: Improvement at week 14 was maintained 2 years later. Clinician-accompanied exposure and self-exposure did not differ on any measure. Compliance with self-exposure homework during weeks 0-8 predicted more improvement 2 years later. Patients who failed to improve with relaxation by week 14 improved after subsequent crossover to exposure. A need for more treatment for their phobias was still felt by 33 patients (49%). CONCLUSIONS: Patients with phobias maintained their improvement to 2-year follow-up after the end of self-exposure therapy.

Adult↗
PubMed2001

Cell-based screening approach for antitumor drug leads which exploits sensitivity differences between normal and cancer cells: identification of two novel cell-cycle inhibitors.

A cell-based in vitro screening approach for identification of antitumor drug leads that exploits the differential sensitivity between normal and cancer cells was developed. It is a three-step, high-throughput screen for antiproliferative and/or cytotoxic activity measured by a 7 day MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromidel assay using small panels of proliferating primary human cells and established cancer cell lines. Proof-of-concept experiments successfully identified 11 known cancer drugs randomly mixed with 5000 test compounds. Application of this screening approach to a library of 110000 compounds allowed for the identification of several novel chemical classes of compounds active against an expanded panel of cancer cell lines in vitro. Two of the compounds representing novel mitotic inhibitors with in vivo potency against established breast cancer xenografts (MDA-MB-435) are reported here.

Antineoplastic Agents↗
PubMed2000

Neurological and neuropsychological signs in obsessive compulsive disorder: interaction with behavioural treatment.

The main aim of this study was to test the hypothesis that neurological soft signs and neuropsychological abnormalities associated with obsessive-compulsive disorder (OCD) predict poor response to behavioural treatment. The design permitted investigation of secondary hypotheses, regarding correlations among these neurological markers and levels of symptomatology, and their stability in relation to changes in levels of symptomatology. Thirty-five participants satisfying DSM-IV diagnostic criteria for OCD were assessed pre- and postbehavioural treatment using a scaled measure of symptom severity, and a battery of tests sensitive to neuropsychological deficits associated with OCD. Eighteen of the participants were also assessed on an inventory of neurological soft signs. Neither neuropsychological test deficits nor neurological soft signs pretreatment predicted response to behavioural treatment. Lower performance on neuropsychological tasks and symptom severity were both significantly correlated with levels of soft signs. Some neurological markers were less severe posttreatment, but these changes were not related to treatment response.

Adolescent↗
PubMed2000

A differential neural response in obsessive-compulsive disorder patients with washing compared with checking symptoms to disgust.

BACKGROUND: Patients with obsessive-compulsive disorder (OCD) have symptoms that predominantly concern washing (washers) or checking (checkers), or both. Functional neuroimaging has been used to identify the neural correlates of the urge to ritualize but has not distinguished between washing and checking symptoms in OCD. We used functional magnetic resonance imaging to compare the neural response to emotive pictures in washers and checkers. METHODS: In one of two 5-minute experiments, washers (N = 7), checkers (N = 7) and age-matched normal controls (N = 14) were scanned while viewing alternating blocks of normally disgusting (rated as disgusting by all subjects) and neutral pictures. In the other experiment, all patients and a normal subgroup (N = 8) viewed alternating blocks of washer-relevant (rated as more disgusting by washers than normal controls or checkers) and neutral pictures. RESULTS: In all subjects, normally disgusting pictures activated visual regions implicated in perception of aversive stimuli and the insula, important in disgust perception. Only in washers were similar regions activated by washer-relevant pictures. In checkers, these pictures activated fronto-striatal regions associated with the urge to ritualize in OCD. Normal controls were more similar in neural response to checkers than washers to these pictures. Both normal controls and checkers had frontal regions activated significantly more by washer-relevant than normally disgusting pictures, and had these regions activated significantly more than washers by washer-relevant pictures. CONCLUSIONS: We demonstrate a differential neural response to washer-relevant disgust in washers and checkers: only washers demonstrate a neural response to washer-relevant disgust associated with emotion perception rather than attention to non-emotive visual detail.

Adolescent↗
PubMed2000

Subjective imagery in obsessive-compulsive disorder before and after exposure therapy. Pilot randomised controlled trial.

BACKGROUND: Distressing mental imagery is hard to study experimentally in obsessive--compulsive disorder (OCD). AIMS: To develop a way to assess mental imagery in OCD during functional magnetic resonance imaging (fMRI). METHOD: A small randomised study, controlled for type and order of mental imagery and for treatment condition (exposure therapy guided by a computer or by a therapist, or relaxation guided by audio-tape). Before and after treatment, during fMRI scanning, patients imagined previously-rehearsed scenarios that evoked an urge to ritualise or non-OCD anxiety or a neutral state, and rated their discomfort during imagery. RESULTS: The method evoked greater discomfort during OCD imagery and anxiety (non-OCD) imagery than during neutral imagery. Discomfort was reduced by cancelling imagery. Discomfort during OCD imagery (but not during anxiety non-OCD imagery) fell after exposure therapy but not after relaxation. CONCLUSIONS: Results showed differences between OCD and non-OCD images and their change after successful treatment, and confirmed clinical suggestions that cancelling images reduced OCD discomfort. The method's success paves the way for further studies of mental imagery in OCD: for instance, during fMRI.

Adult↗
PubMed2000

Self-treatment of obsessive-compulsive disorder guided by manual and computer-conducted telephone interview.

While on a waiting list for treatment by therapist-guided exposure and ritual prevention (ERP), patients with obsessive-compulsive disorder (OCD) did self-treatment at home guided by a manual plus a computer-driven telephone interview system (BT STEPS). Of 21 patients who used the system for at least three weeks while on the waiting list, one improved so much that subsequent therapist-guided ERP was unnecessary. Progress of the rest with the system predicted later progress with therapist-guided ERP. Improvement after using the system was similar to that of 20 matched historical controls who had had therapist-guided ERP without the prior use of BT STEPS. Outpatient users of BT STEPS needed less subsequent clinician-guided time than did their matched controls. In this pilot study, patients with OCD improved nearly as much with home self-treatment guided by a manual plus computer, as with treatment guided by a behaviour therapist.

Adult↗
PubMed1999

Long-term effects of alprazolam on memory: a 3.5 year follow-up of agoraphobia/panic patients.

BACKGROUND: Benzodiazepines (BZs) can impair explicit memory after a single dose and also when taken repeatedly for treatment of anxiety disorders. A previous study with agoraphobia/panic patients found that the BZ alprazolam impaired memory during an 8-week treatment and residual impairments were still manifest several weeks after drug withdrawal (Curran et al. 1994). The present study followed up the same group of patients 3.5 years after treatment to determine whether those memory impairments persisted. METHOD: Thirty-one patients, 15 who had originally been treated with alprazolam and 16 with placebo, were assessed on a battery of psychometric tests and self-rating scales. RESULTS: Ex-alprazolam patients performed at the same levels as ex-placebo patients on the memory task and on other objective tests. Performance levels of both groups were similar to pre-treatment baselines, however there were differences in subjective ratings whereby ex-alprazolam patients rated themselves as less attentive and clear headed and more incompetent and clumsy than ex-placebo patients. CONCLUSIONS: Explicit memory impairments found while patients were taking alprazolam and weeks after drug withdrawal did not persist 3.5 years later. We suggest that the memory impairments observed in our previous study weeks after withdrawal of alprazolam were not residual effects of alprazolam but rather were due to the drug's interference with practice effects on the tests and habituation of anxiety over repeated exposure to the test situation.

Adult↗
PubMed1999

Home self-assessment and self-treatment of obsessive-compulsive disorder using a manual and a computer-conducted telephone interview: replication of a UK-US study.

BACKGROUND: This open study replicates and extends previous pilot work with BT STEPS, a self-therapy system to assess and treat obsessive-compulsive disorder (OCD) through exposure and ritual prevention. METHOD: 21 OCD patients entered this open trial, using a self-guiding manual and any Touch-Tone telephone to access computer-driven interviews via an Interactive Voice Response system. The patients also used the system to rate progress on rating scales. RESULTS: The results support those of the previous open study. Of the 21 patients, 16 (76%) completed self-assessment over a mean of 21 days. Of these, 10 patients (48%) went on to do 2 or more exposure and ritual prevention sessions over a mean of 64 days; they improved significantly on OCD symptoms, as much as is usual with serotonin reuptake inhibitor medication, and in mood and work/social adjustment. Improvement was predicted by baseline motivation and by rapid completion of self-assessment with BT STEPS, even though self-assessment alone was not therapeutic. CONCLUSION: The significant improvement in the intent-to-treat analysis was due to the subgroup of patients (48% of those who began BT STEPS) who went beyond self-assessment to do exposure and ritual prevention self-therapy at home guided by BT STEPS. A controlled trial is now needed.

Adult↗
PubMed1998

Home self-assessment of obsessive-compulsive disorder. Use of a manual and a computer-conducted telephone interview: two UK-US studies.

BACKGROUND: Two studies tested whether subjects with obsessive-compulsive disorder could successfully use BT STEPS, a computer-aided system, to perform self-assessment for self-treatment of obsessive-compulsive disorder by exposure and ritual prevention. METHOD: Subjects were given a self-guiding manual and could use a touch-tone telephone to access computer-controlled Interactive Voice Response interviews at their convenience from home. Using the BT STEPS system, patients rated themselves and worked out a plan for individually tailored self-exposure therapy. RESULTS: Outcomes were similar in the two studies. Of the 63 subjects who used BT STEPS, 84% completed the self-assessment module. Most calls were made outside usual office hours. As expected, subjects did not improve merely by completing self-assessment. However, completion of self-assessment predicted later improvement with self-exposure therapy. CONCLUSIONS: Most subjects successfully completed self-assessment using BT STEPS from their homes. DECLARATION OF INTEREST: BT STEPS is a trademark of Pfizer, Inc. I.M.M., L.B. and J.H.G. have a financial interest in BT STEPS.

Adult↗
PubMed1998

A pilot study of computer-aided vicarious exposure for obsessive-compulsive disorder.

OBJECTIVE: This study reports the use of an interactive computer program to instruct vicarious exposure and ritual prevention for obsessive-compulsive disorder (OCD). METHOD: Thirteen OCD volunteers and 10 non-OCD volunteers completed three 45-minute sessions at weekly intervals. Subjects with OCD completed the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Padua Inventory (PI) and the Beck Depression Inventory (BDI) 1 week prior to and 1 week after the three computer treatment sessions. Non-OCD subjects only completed these measures at baseline, allowing confirmation that they had no significant level of OCD symptomatology. RESULTS: In the OCD subjects, scores fell significantly on the PI and BDI, and Y-BOCS scores fell non-significantly. Engagement in vicarious exposure with ritual prevention improved from sessions 1-3. Compared to the non-OCD participants, OCD subjects did less vicarious exposure in session 1 but not sessions 2 and 3. Performance of vicarious exposure by OCD subjects in session 1 correlated with pre-post improvement in PI and BDI scores. CONCLUSIONS: The vicarious exposure program may have a role to play as an adjunct in behaviour therapy.

Adolescent↗
PubMed1998

Self-administered psychotherapy for depression using a telephone-accessed computer system plus booklets: an open U.S.-U.K. study.

OBJECTIVE: To evaluate the efficacy and acceptability of a self-help program for mild-to-moderate depression that combined treatment booklets and telephone calls to a computer-aided Interactive Voice Response (IVR) system. METHOD: In an open trial, 41 patients from Boston, Massachusetts; Madison, Wisconsin; and London, England, used COPE, a 12-week self-help system for depression. COPE consisted of an introductory videotape and 9 booklets accompanied by 11 telephone calls to an IVR system that made self-help recommendations to patients based on information they entered. RESULTS: All 41 patients successfully completed the self-assessment in the booklets and telephone calls; 28 (68%) also completed the 12-week self-help program. Hamilton Rating Scale for Depression (HAM-D) and Work and Social Adjustment scores improved significantly (41% and 42% mean reduction in the intent-to-treat sample, respectively, p < .001). Eighteen (64%) of the 28 completers were considered responders on the basis of > or = 50% reduction in their HAM-D scores. There was a higher percentage of completers in the pooled U.S. sites (82% vs. 43%), and U.S. completers improved more than those in the United Kingdom (73% vs. 43% were responders). Most (68%) of the calls were made outside usual office hours, Monday-Friday, 9:00 a.m. to 5:00 p.m. Expectation of effectiveness and time spent making COPE calls (more treatment modules) correlated positively with improvement over 12 weeks. Mean call length for completers was 14 minutes. CONCLUSION: A self-help system comprised of a computer-aided telephone system and a series of booklets was used successfully by people with mild-to-moderate depression. These preliminary results are encouraging for people who cannot otherwise access ongoing, in-person therapy.

Adult↗
PubMed1997

Caudate regional cerebral blood flow in obsessive-compulsive disorder, panic disorder and healthy controls on single photon emission computerised tomography.

We compared regional cerebral blood flow (rCBF) in 15 patients with DSM IIIR obsessive-compulsive disorder (OCD), 15 patients with DSM IIIR panic disorder and 15 healthy controls matched for age, sex and hand preference, using uptake of technetium-99m-D,L-hexamethyl-propylene amine oxime (99mTc HMPAO), on single photon emission computerised tomography (SPECT). Caudate rCBF was significantly reduced in OCD patients compared to healthy subjects and panic disorder patients. When four patients were excluded from each group, right caudate rCBF remained significantly lower in OCD patients than in panic disorder patients or healthy subjects. The data suggest functional involvement of the right caudate nucleus is present in OCD.

Adult↗
PubMed1997

Wisconsin Card Sorting Task (WCST) errors and cerebral blood flow in obsessive-compulsive disorder (OCD).

We compared Wisconsin Card Sorting Task (WCST) performance in 19 obsessive-compulsive disorder (OCD) patients and 19 individually matched healthy controls. Measures of intelligence and mood were taken into account for all participants. Within the patient group, factors such as duration and severity of symptoms (as assessed using the Yale-Brown Obsessive-Compulsive Scale, Y-BOCS) were considered. We explored the relationship between OCD WCST errors and regional cerebral blood flow (rCBF) on brain dedicated, high resolution, single photon emission tomography (SPET). We used uptake of 99mTc-hexamethylpropylamine oxime (HMPAO) on SPET to estimate rCBF, and regional values were quantified as ratios of cerebellar blood flow. WCST results confirmed OCD patients were significantly impared when compared with age- and sex-matched healthy volunteers. Patients made significantly more trials, more preseverative errors, and more null-sorts. OCD patients Y-BOCS 'obsessive' subtotal significantly correlated with many WCST errors. Furthermore OCD WCST null-sorts correlated significantly with SPET OCD left inferior frontal cortical rCBF (r(18) = .47, p = .05) and left caudate rCBF (r(18) = .72, p = .01). The implications of these findings are discussed in the context of other studies which examine functional imaging and neuropsychology in OCD.

Adult↗
PubMed1997

trans-Dominant and non-trans-dominant mutant simian virus 40 large T antigens show distinct responses to ATP.

Simian virus 40 (SV40) DNA replication requires the coordinated action of multiple biochemical activities intrinsic to the virus-encoded large tumor antigen (T antigen). We report the preliminary biochemical characterization of the T antigens encoded by three SV40 mutants, 5030, 5031, and 5061, each of which have altered residues within or near the ATP binding pocket. All three mutants are defective for viral DNA replication in cultured cell lines. However, while 5030 and 5031 can be complemented in vivo by providing a wild-type T antigen in trans, 5061 exhibits a strong trans-dominant-negative phenotype. In order to determine the basis for their replication defects and to explore the mechanisms of trans dominance, we purified the T antigens encoded by each of these mutants and examined their activities in vitro. The 5061 T antigen had no measurable ATPase activity and failed to hexamerize in response to ATP, and its affinity for the SV40 origin of DNA replication (ori) DNA was not increased by ATP. In contrast, the 5030 and 5031 T antigens exhibited at least some ATPase activity and both readily formed hexamers in the presence of ATP. These mutants differed in that 5030 was very defective in an ori-dependent unwinding assay while 5031 retained significant activity. Both the 5030 and 5031 T antigens bound to ori-containing DNA, but the binding was less efficient than that of wild-type T antigen and was not affected by the presence of ATP. These results suggest that 5030 and 5031 are defective in some aspect of communication between the ATP binding and DNA binding domains and that the ability of ATP to induce T-antigen hexamerization is distinct from its action to increase the affinity for ori. Finally, all three mutants were defective for the ability to support SV40 DNA replication in vitro. Both the 5031 and 5061 T antigens inhibited wild-type-T-antigen-stimulated replication in vitro, while the 5030 T antigen did not. The fact that the 5031 T antigen was trans dominant in the in vitro assays but not in vivo indicates that the in vitro system does not accurately reflect events occurring in vivo.

Adenosine Triphosphatases↗