Recurrent images and early memories in social phobia.

A recent model [Clark, D. M. & Wells, A. (1995). A cognitive model of social phobia. In R. Heimberg, M. Liebowitz, D. A. Hope & F. R. Schneier (Eds.), Social phobia: diagnosis, assessment and treatment (pp. 69-93). New York: Guildford Press] suggests that a distorted image of one's public self lies at the heart of social phobia. A previous study of spontaneous imagery [Hackmann, A., Surawy, C. & Clark, D. M. (1998) Seeing yourself through others' eyes: a study of spontaneously occurring images in social phobia. Behavioural and Cognitive Psychotherapy, 26, 3-12] confirmed that patients with social phobia frequently report experiencing negative, distorted, observer-perspective images when in anxiety provoking social situations. In the present study, 22 patients with social phobia were given a semistructured interview which aimed to further explore the nature of social phobic imagery. All participants were able to identify negative spontaneous images that were recurrent in the sense that their content appeared to be relatively stable over time and across different feared social situations. Most recurrent images involved several sensory modalities. Most recurrent images were linked to memories of adverse social events that clustered in time around the onset of the disorder. Taken together, the results suggest that in patients with social phobia, early unpleasant experiences may lead to the development of excessively negative images of their social selves that are repeatedly activated in subsequent social situations and fail to update in the light of subsequent, more favourable experiences. Implications of the findings for the understanding and treatment of social phobia are discussed.

Brief cognitive therapy for panic disorder: a randomized controlled trial.

Cognitive therapy (CT) is a specific and highly effective treatment for panic disorder (PD). Treatment normally involves 12-15 1-hr sessions. In an attempt to produce a more cost-effective version, a briefer treatment that made extensive use of between-sessions patient self-study modules was created. Forty-three PD patients were randomly allocated to full CT (FCT), brief CT (BCT), or a 3-month wait list. FCT and BCT were superior to wait list on all measures, and the gains obtained in treatment were maintained at 12-month follow-up. There were no significant differences between FCT and BCT. Both treatments had large (approximately 3.0) and essentially identical effect sizes. BCT required 6.5 hr of therapist time, including booster sessions. Patients' initial expectation of therapy success was negatively correlated with posttreatment panic-anxiety. Cognitive measures at the end of treatment predicted panic-anxiety at 12-month follow-up.

Different somatic and germline HPRT1 mutations promote use of a common, cryptic intron 1 splice site. Mutation in brief no. 259. Online.

Aberrant hypoxanthine phosphoribosyltransferase (HUGO-approved gene symbol HPRT1; MIM# 308000) RNA splicing promoted by splice site mutation or loss is a common mechanism for loss of the purine salvage enzyme HPRT1 from human cells. We report here two in vivo somatic HPRT1 mutations in human kidney tubular epithelial cells that disrupt HPRT1 intron 1 splicing and lead to the inclusion of intron 1 sequence in mature mRNA. Analysis of these mutations and of 14 additional HPRT1 intron 1 inclusion mutations provides an explanation for use of a common, cryptic intron 1 splice donor site by all 16 mutations.

Different somatic and germline HPRT1 mutations promote use of a common, cryptic intron 1 splice site. Mutations in brief no. 246. Online.

Aberrant hypoxanthine phosphoribosyltransferase (HUGO-approved gene symbol HPRT1; MIM# 308000) mRNA splicing, promoted by splice site mutation or loss, is a common mechanism for loss of the purine salvage enzyme HPRT1 from human cells. We report here two in vivo somatic HPRT1 mutations in human kidney tubular epithelial cells that disrupt HPRT1 intron 1 splicing and lead to the inclusion of intron 1 sequence. We propose an explanation for the use of a common, cryptic intron 1 splice donor site by these two mutations, and by 14 additional human HPRT1 mutations that lead to aberrant splicing with the incorporation of intron 1 sequence into mRNA.

An experimental investigation of the role of safety-seeking behaviours in the maintenance of panic disorder with agoraphobia.

This study evaluates the hypothesis that safety-seeking behaviours play an important role in maintaining anxiety because they prevent patients from benefiting from disconfirmatory experience. Patients suffering from panic disorder with agoraphobia carried out a behaviour test, closely followed by an experimental session, which included a brief (15 min) period of exposure during which participants either stopped or maintained within-situation safety-seeking behaviours. When the behaviour test was repeated within two days, patients who had stopped their safety-seeking behaviours during the experimental session showed a significantly greater decrease in catastrophic beliefs and anxiety than those who had maintained safety-seeking behaviour. This difference was also reflected in questionnaires measuring clinical anxiety. These results are consistent with the cognitive hypothesis.

Generation of highly site-specific DNA double-strand breaks in human cells by the homing endonucleases I-PpoI and I-CreI.

We have determined the ability of two well-characterized eukaryotic homing endonucleases, I-PpoI from the myxomycete Physarum polycephalum and I-CreI from the green alga Chlamydomonas reinhardtii, to generate site-specific DNA double-strand breaks in human cells. These 18-kDa proteins cleave highly conserved 15- or 24-bp rDNA homing sites in their respective hosts to generate homogeneous 4-base, 3' ends that initiate target intron transposition or "homing." We show that both endonucleases can be expressed in human cells and can generate site-specific DNA double-strand breaks in 28S rDNA and homing site plasmids. These endonuclease-induced breaks can be repaired in vivo, although break repair is mutagenic with the frequent generation of short deletions or insertions. I-PpoI and I-CreI should be useful for analyzing DNA double-strand break repair in human cells and rDNA.

Two psychological treatments for hypochondriasis. A randomised controlled trial.

BACKGROUND: Hypochondriasis is generally considered difficult to manage. This study aimed to assess the effectiveness of cognitive therapy and to compare it with an equally credible, alternative treatment. METHOD: Forty-eight patients with hypochondriasis were initially randomly assigned to either cognitive therapy, behavioural stress management or a no treatment waiting list control group. At the end of the waiting period, patients in the control group were randomly assigned to one of the two treatments. Assessments were at pre-, mid- and post-treatment or waiting list and at three-, six- and 12-month post-treatment follow-up. RESULTS: Comparisons with the waiting list group showed both treatments were effective. Comparisons between the treatments showed that cognitive therapy was more effective than behavioural stress management on measures of hypochondriasis, but not general mood disturbance at mid-treatment and at post-treatment. One year after treatment patients who had received either treatment remained significantly better than before treatment, and on almost all measures the two therapies did not differ from each other. CONCLUSIONS: Cognitive therapy is a specific treatment for hypochondriasis. Behavioural stress management is also effective but its specificity remains to be demonstrated.

Extension of the Rorschach--Hazlewood theoretical model for spin-lattice relaxation in biological systems to low frequencies.

The water-biopolymer cross-relaxation model, proposed by H. E. Rorschach and C. F. Hazlewood (RH) [J. Magn. Reson. 70, 79 (1986)], explains the Larmor frequency dependence of T1 in many biological systems. However, the RH theory fails at low Larmor frequencies. In this paper, a more general version of the RH theory has been developed. This theory is valid at all frequencies. Use of the new expression for the spin-lattice relaxation rate (1/T1), earlier published experimental data in H2O/D2O bovine serum albumin, which had been measured over a wide frequency range (10 kHz to 100 MHz), were fitted over the entire frequency range. The agreement between theory and the experimental data is excellent. Theoretical expressions for the rotating-frame spin-lattice relaxation rate (1/T1(rho)) were also obtained.

Application to rat lung of the extended Rorschach-Hazlewood model of spin-lattice relaxation.

The spin-lattice relaxation time T1 was measured in excised degassed (airless) rat lungs over the frequency range 6.7 to 80.5 MHz. The observed frequency dependence was fitted successfully to the water-biopolymer cross-relaxation theory proposed by H. E. Rorschach and C. F. Hazlewood (RH) [J. Magn. Reson. 70, 79 (1986)]. The rotating frame spin-lattice relaxation time T1(rho) was also measured in rat lung fragments over the frequency range 0.56 to 5.6 kHz, and the observed frequency dependence was explained with an extension of the RH model. The agreement between the theory and the experimental data in both cases is good.

Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial.

OBJECTIVE: To evaluate the acceptability and efficacy of adding cognitive behaviour therapy to the medical care of patients presenting with the chronic fatigue syndrome. DESIGN: Randomised controlled trial with final assessment at 12 months. SETTING: An infectious diseases outpatient clinic. SUBJECTS: 60 consecutively referred patients meeting consensus criteria for the chronic fatigue syndrome. INTERVENTIONS: Medical care comprised assessment, advice, and follow up in general practice. Patients who received cognitive behaviour therapy were offered 16 individual weekly sessions in addition to their medical care. MAIN OUTCOME MEASURES: The proportions of patients (a) who achieved normal daily functioning (Karnofsky score 80 or more) and (b) who achieved a clinically significant improvement in functioning (change in Karnofsky score 10 points or more) by 12 months after randomisation. RESULTS: Only two eligible patients refused to participate. All randomised patients completed treatment. An intention to treat analysis showed that 73% (22/30) of recipients of cognitive behaviour therapy achieved a satisfactory outcome as compared with 27% (8/30) of patients who were given only medical care (difference 47 percentage points; 95% confidence interval 24 to 69). Similar differences were observed in subsidiary outcome measures. The improvement in disability among patients given cognitive behaviour therapy continued after completion of therapy. Illness beliefs and coping behaviour previously associated with a poor outcome changed more with cognitive behaviour therapy than with medical care alone. CONCLUSION: Adding cognitive behaviour therapy to the medical care of patients with the chronic fatigue syndrome is acceptable to patients and leads to a sustained reduction in functional impairment.

Chronic fatigue syndrome: a cognitive approach.

Observations concerning the characteristics of patients who presented to a medical clinic with a principal complaint of chronic medically unexplained fatigue (Chronic Fatigue Syndrome or CFS) are described, including the cognitions (thoughts and assumptions) elicited from a sample of these patients who were treated using cognitive behavioural therapy. On the basis of these observations a cognitive theory of the aetiology of CFS is proposed. These observations have implications for the treatment of patients with CFS.

[Function of the glenohumeral ligaments in active protection of shoulder stability]. / Uber die Funktion der glenohumeralen Ligamente bei der aktiven Sicherung der Schulterstabilität.

UNLABELLED: We harvested the joint capsule, the glenohumeral ligaments, and the coracohumeral ligaments of 8 fresh formalin-preserved shoulder specimen. We made use of the van Gieson technique and a special silver impregnation for staining peripheral axons according to Nowotny. The ligaments were cut into slices with a thickness of 15 microns. In total we performed 10,000 cuts. We discovered axons in all ligaments. These axons had no relation to vessels or vessel walls. Besides these axonal structures we detected type II mechanoreceptors (Pacini receptor). CLINICAL SIGNIFICANCE: The neural structures discovered in the glenohumeral capsule are of clinical importance especially in consideration of the high account of recurrent shoulder dislocation and concomitant Bankart lesions. Receptors located in the glenohumeral ligaments might control the stabilizing shoulder musculature. On this premises, rupture or detachment of these ligaments will lead to a loss of the feedback mechanism.

A comparison of cognitive therapy, applied relaxation and imipramine in the treatment of panic disorder.

Recent studies have shown that cognitive therapy is an effective treatment for panic disorder. However, little is known about how cognitive therapy compares with other psychological and pharmacological treatments. To investigate this question 64 panic disorder patients were initially assigned to cognitive therapy, applied relaxation, imipramine (mean 233 mg/day), or a 3-month wait followed by allocation to treatment. During treatment patients had up to 12 sessions in the first 3 months and up to three booster sessions in the next 3 months. Imipramine was gradually withdrawn after 6 months. Each treatment included self-exposure homework assignments. Cognitive therapy and applied relaxation sessions lasted one hour. Imipramine sessions lasted 25 minutes. Assessments were before treatment/wait and at 3, 6, and 15 months. Comparisons with waiting-list showed all three treatments were effective. Comparisons between treatments showed that at 3 months cognitive therapy was superior to both applied relaxation and imipramine on most measures. At 6 months cognitive therapy did not differ from imipramine and both were superior to applied relaxation on several measures. Between 6 and 15 months a number of imipramine patients relapsed. At 15 months cognitive therapy was again superior to both applied relaxation and imipramine but on fewer measures than at 3 months. Cognitive measures taken at the end of treatment were significant predictors of outcome at follow-up.

Function of the glenohumeral ligaments in active stabilisation of the shoulder joint.

UNLABELLED: The joint capsules and the glenohumeral ligaments of 12 human shoulder specimens were histologically investigated by light microscopy. Serial sections of 15 microns thickness were cut. The tissue was stained following the haematoxylin-eosin and van Giesson techniques. For specific identification of neural elements we made use of a special silver impregnation technique, described by Novotny, for staining axons in peripheral nerves. Axons of different diameters ranging from 0.2 microns to 70 microns were discovered within the ligaments. Close to the humeral site we found small nerves forming neurovascular bundles. Within their connective tissue sheaths, the axons exhibited a serpentine configuration, which may give extra length and may allow stretching of the nerve during motion. Most of the axons discovered were located in the subsynovial layer of the ligaments. In general the diameter of these subsynovial axons did not exceed 10 microns. In addition to these axonal structures, we detected nerve endings which can be classified according to Freeman and Wyke as type II mechanoreceptors (Pacinian corpuscles). These mechanoreceptors had a diameter of approximately 150 microns. They were also positioned directly beneath the synovial membrane and close to the humeral site of insertion of the ligaments. CLINICAL SIGNIFICANCE: The described neural structures in the glenohumeral ligaments are of particular clinical importance in the light of the high incidence of recurrent shoulder dislocation and concomitant Bankart lesions. The mechanoreceptors located in the glenohumeral ligaments may control the stabilising shoulder musculature. On this premise, rupture or detachment of these ligaments will lead to a loss of a feedback mechanism.

Nucleotide sequence analysis of human hypoxanthine phosphoribosyltransferase (HPRT) gene deletions.

We have determined the nucleotide sequences of 10 intragenic human HPRT gene deletion junctions isolated from thioguanine-resistant PSV811 Werner syndrome fibroblasts or from HL60 myeloid leukemia cells. Deletion junctions were located by fine structure blot hybridization mapping and then amplified with flanking oligonucleotide primer pairs for DNA sequence analysis. The junction region sequences from these 10 HPRT mutants contained 13 deletions ranging in size from 57 bp to 19.3 kb. Three DNA inversions of 711, 368, and 20 bp were associated with tandem deletions in two mutants. Each mutant contained the deletion of one or more HPRT exon, thus explaining the thioguanine-resistant cellular phenotype. Deletion junction and donor nucleotide sequence alignments suggest that all of these HPRT gene rearrangements were generated by the nonhomologous recombination of donor DNA duplexes that share little nucleotide sequence identity. This result is surprising, given the potential for homologous recombination between copies of repeated DNA sequences that constitute approximately a third of the human HPRT locus. No difference in deletion structure or complexity was observed between deletions isolated from Werner syndrome or from HL60 mutants. This suggests that the Werner syndrome deletion mutator uses deletion mutagenesis pathway(s) that are similar or identical to those used in other human somatic cells.

Molecular structure and genetic stability of human hypoxanthine phosphoribosyltransferase (HPRT) gene duplications.

We have determined the genetic stability of three independent intragenic human HPRT gene duplications and the structure of each duplication at the nucleotide sequence level. Two of the duplications were isolated as spontaneous mutations from the HL60 human myeloid leukemia cell line, while the third was originally identified in a Lesch-Nyhan patient. All three duplications are genetically unstable and have a reversion rate approximately 100-fold higher than the rate of duplication formation. The molecular structures of these duplications are similar, with direct duplication of HPRT exons 2 and 3 and of 6.8 kb (HL60 duplications) or 13.7 kb (Lesch-Nyhan duplication) of surrounding HPRT sequence. Nucleotide sequence analyses of duplication junctions revealed that the HL60-derived duplications were generated by unequal homologous recombination between clusters of Alu repeats contained in HPRT introns 1 and 3, while the Lesch-Nyhan duplication was generated by the nonhomologous insertion of duplicated HPRT DNA into HPRT intron 1. These results suggest that duplication substrates of different lengths can be generated from the human HPRT exon 2-3 region and can undergo either homologous or nonhomologous recombination with the HPRT locus to form gene duplications.

Treatment of panic attacks using cognitive therapy without exposure or breathing retraining.

Cognitive treatment of panic attacks is based on the hypothesis that panic results from the catastrophic misinterpretation of bodily sensations, and that changing such misinterpretations will block the occurrence of panic. The treatment normally involves an integrated set of cognitive and behavioural techniques. In a consecutive series of panic patients, a multiple baseline across subjects design was used to investigate whether a modified form of treatment involving only cognitive procedures could reduce panic attack frequency. The results provide preliminary evidence that cognitive procedures directed at changing misinterpretations of bodily sensations can reduce panic attack frequency, and also that cognitive procedures which do not target misinterpretations may not reduce panic.