A pilot study augmenting cognitive behavioral therapy for panic disorder with attention bias modification: Clinical and psychophysiological outcomes.

BACKGROUND AND OBJECTIVES: Studies show that attentional bias towards threat is a key maintenance factor for panic disorder (PD). Attentional bias may be an important mechanism of symptom reduction, and thus, a useful target for optimizing outcomes. The current study examined whether an attention bias modification (ABM) task enhanced CBT outcomes. Multiple methods for assessing PD were used, including physiological measurement and clinician-rated assessment. METHODS: Adults with panic disorder (N = 24) received seven sessions of CBT with either ABM or sham attention tasks. Psychophysiological reaction to a loud tones startle paradigm was assessed before and after treatment. RESULTS: Across both groups, panic symptom severity decreased with CBT. The ABM group showed greater reductions in PD symptoms compared to the placebo group. Notably, however, changes in attentional bias were not associated with symptom reductions across groups. No significant group differences on psychophysiological assessment were observed. LIMITATIONS: This study is limited by the small sample size, which rendered our power to investigate mediators and moderators insufficient. More research is needed to validate the effect of attention bias modification on attentional bias to threat. CONCLUSIONS: This pilot study suggests that future research should investigate attentional bias in conjunction with CBT. A larger sample would provide opportunity to further investigate the mechanisms through which ABM works, along with potential moderating factors and the use of psychophysiological measurements in panic disorder.

Coccygectomy: an effective treatment option for chronic coccydynia: retrospective results in 41 consecutive patients.

Between 1993 and 2008, 41 patients underwent total coccygectomy for coccydynia which had failed to respond to six months of conservative management. Of these, 40 patients were available for clinical review and 39 completed a questionnaire giving their evaluation of the effect of the operation. Excellent or good results were obtained in 33 of the 41 patients, comprising 18 of the 21 patients with coccydynia due to trauma, five of the eight patients with symptoms following childbirth and ten of 12 idiopathic onset. In eight patients the results were moderate or poor, although none described worse pain after the operation. The only post-operative complication was superficial wound infection which occurred in five patients and which settled fully with antibiotic treatment. One patient required re-operation for excision of the distal cornua of the sacrum. Total coccygectomy offered satisfactory relief of pain in the majority of patients regardless of the cause of their symptoms.

Similar regulatory mechanisms despite differences in membrane lipid composition in Acholeplasma laidlawii strains A-EF22 and B-PG9. A multivariate data analysis.

Mycoplasmas are small, cell wall-deficient bacteria. The metabolic regulation of the lipid composition in the membrane of the species Acholeplasma laidlawii, strains A-EF22 and B-JU, is governed mainly by the balance between the potential formation of lamellar and nonlamellar phase structures. However, the regulatory features have not been consistently observed in the B-PG9 strain. A comparison has been performed between the membrane lipid composition for strains A-EF22 and B-PG9, simultaneously changing eight experimental conditions known to affect the regulation and packing properties of the A-EF22 lipids. Multiple regression and partial least-square discriminant analyses of many variables showed: (i) quantitative differences in membrane lipid and protein composition, and in membrane protein molecular masses of the two strains; (ii) different molar fractions of the major polar lipids monoglucosyldiacylglycerol (nonlamellar) and diglucosyldiacylglycerol (lamellar), which were caused by differences in lipid acyl chain length and unsaturation inherent in the strains and by the type of growth medium used; and (iii) similar regulatory mechanisms for changes in the lipid composition under most conditions, responding to the experimentally varied bilayer and nonbilayer properties of the lipid matrix. These regulatory principles are probably valid in other bacteria as well.

A strategy for ranking environmentally occurring chemicals. Part VI. QSARs for the mutagenic effects of halogenated aliphatics.

A strategy for the systematic analysis and priority ranking of environmental chemicals has been applied to a class of 58 halogenated aliphatic hydrocarbons. A training set of ten compounds representing this class, was selected by statistical design. The training set compounds were then subjected to biological testing in the Salmonella typhimurium reverse mutation assay (Ames test). The measured biological data, recorded as dose-response curves, were analyzed to determine the mutagenic potency (slope of the initial portion) and the mutagen dose (MD 50) required to increase the number of revertants above the background by 50%. For each compound, four mutagenic potency estimates and four MD 50 values were determined, all originating from the tester strains TA 100 and TA 1535 with and without metabolic activation. The obtained responses were analyzed with multivariate techniques to give QSAR models relating the mutagenic potency data to the physico-chemical properties of the compounds. Finally, the derived QSARs were used to predict the mutagenic potencies and the MD 50S for the non-tested compounds in the class.

Minimum analogue peptide sets (MAPS) for quantitative structure-activity relationships.

The information contents in previously published peptide sets was compared with smaller sets of peptides selected according to statistical designs. It was found that minimum analogue peptide sets (MAPS) constructed by factorial or fractional factorial designs in physiochemical properties contained substantial structure-activity information. Although five to six times smaller than the originally published peptide sets the MAPS resulted in QSAR models able to predict biological activity. The QSARs derived from a MAPS of nine dipeptides, and from a set of 58 dipeptides inhibiting angiotensin converting enzyme were compared and found to be of equal strength. Furthermore, for a set of bitter tasting dipeptides it was found that an incomplete MAPS of 10 dipeptides gave just as good a model as the model based on a set of 48 dipeptides. By comparison other non-designed sets of peptides gave QSARs with poor predictive power. It was also demonstrated how MAPS centered on a lead peptide can be constructed as to specifically explore the physiochemical and biological properties in the vicinity of the lead. It was concluded that small information-rich peptide sets MAPS can be constructed on the basis of statistical designs with principal properties of amino acids as design variables.

A multivariate representation and analysis of DNA sequence data.

A new way to represent and analyze DNA sequence data is described. This approach complements methods currently used, in that it allows the systematic part of the variation between different sequences to be modeled. This can prove as informative as absence of variation (homology), which is the most widely used criterion for comparing sequence data. A multivariate sequence-activity model (SAM), for DNA-promoter sequences is presented, by which the relative promoter strength is modeled in terms of the primary DNA-sequence. The model is shown to have a good predictive capability. The coefficients from the model are interpreted, and used to design new structures predicted to be strong promoters in the system investigated. The approach described is also applicable to other kinds of sequence data, e.g. RNAs, proteins or peptides.

[Colles' fracture. Therapeutic results and use of resources. A comparative study between 2 departments in the same county]. / Fractura Collesi. Behandlingsresultater og ressourceforbrug. En sammenlignende undersøgelse imellem to afdelinger i et amt.

A comparison between the functional end results of Colles' fractures, treated in two different hospitals, was performed by a follow up study of 100 patients from each hospital 18-24 months after fracture. The difference between the requirements of resources in the two hospitals were mainly: treatment of patients as outpatients or during admission and the method of anaesthesia. No significant difference in functional end result between the two groups was found. It was concluded that local anaesthesia in the fracture haematoma often is insufficient and is unpleasant for the patient. A more effective anaesthesia which can be applied polyclinically is preferable, as anaesthesia, which demands admission to the hospital, is an expensive solution and does not give a better functional end result. The "sandwich" type plaster of Paris bandage is more comfortable, safer to use with outpatients and is therefore preferable to the circular plaster of Paris bandage.

Quantitative structure-activity relationships for sea anemone polypeptide toxins.

Sea anemone polypeptides vary considerably in their affinities for sodium channels occurring in different excitable cells. The amino acid sequence variation in a set of six sea anemone type I polypeptide toxins (46-49 residues long), was parameterized using descriptor scales z1, z2, and z3, derived from a large number of amino acid physicochemical properties. The pharmacological properties of the toxins were represented by the results from four bioassays on crab, mouse, and rat brain and from rat heart. By means of the descriptor scales and the multivariate data analytical method PLS (partial least squares projections to latent structures), it was possible to develop quantitative structure-activity relationships (QSAR). Using the QSARs derived from the set of six polypeptide toxins the pharmacological properties of two homologous sea anemone polypeptide toxins were predicted. Thus it is shown that QSARs may be formulated for relatively long bioactive polypeptides. The QSARs indicate that 11 different amino acid positions may be of importance, but that positions no. 5, 21, 28, 34, 37, and 40 were of main importance in modeling the relative toxicities of the six polypeptides.

Coccygodynia treated by resection of the coccyx.

Sixty-five patients suffering from coccygodynia resistant to conservative treatment had total or partial coccygectomy, all without serious complications. Eight reoperations were performed. After an average of 15 years, 46 of the 55 patients seen at follow-up were satisfied. A normal radiograph of the coccyx does not exclude a good result from coccygectomy. We recommend total coccygectomy using a longitudinal incision in carefully selected and well-informed patients.

Peptide QSAR on substance P analogues, enkephalins and bradykinins containing L- and D-amino acids.

Peptide QSARs are constructed for substance P analogues, enkephalins (two examples) and bradykinins containing both L- and D-amino acids. As descriptors in the QSARs, the previously developed descriptors z1 (hydrophobicity), z2 (bulk) and z3 (electronic effect) are used together with a qualitative variable coding for variation in chirality. Two parametrizations of the peptide sequences are tested. In the first no chiral description is used at all, and in the second chirality is described by the qualitative variable. It is concluded that for the current series of peptides, the biological response to variation in amino acid sequence and chirality can be modelled.

Preliminary results from the Scandinavian multicentre evaluation of in vitro cytotoxicity (MEIC).

The multicentre evaluation study of in vitro cytotoxicity tests (MEIC) is organized by the Scandinavian Society of Cell Toxicology. All interested laboratories are invited to test a published list of 50 reference chemicals in their various in vitro assays with a bearing on general toxicity. Submitted results will be centrally evaluated for their relevance to human toxicity, including a comparison with the efficiency of conventional animal tests. This brief communication presents the very first preliminary results of the study, that is, prediction of human acute lethal toxicity for the first 10 MEIC chemicals by all the results submitted to date, that is, five in vitro cytotoxicity assays. As a baseline for judging the efficiency of the cytotoxicity tests, rat and mouse LD(50) values were compared with human acute lethal dosage of the chemicals. Rat LD(50) prediction was relatively poor, but mouse LD(50) values correctly predicted the human lethal dose for six out of the 10 substances. A multivariate method of comparison including all cytotoxicity test results, predicted human lethal blood concentrations as well as the mouse LD(50) prediction of dosage. Since the blood concentrations used in the comparison were derived from human lethal dosage with the help of two simple pharmacokinetic factors (absorbed fraction in the intestine and distribution volume of chemicals), the cytotoxicity assays were found also to be able to predict human dosage, as well as did the mouse LD(50) prediction.

MEIC--a new international multicenter project to evaluate the relevance to human toxicity of in vitro cytotoxicity tests.

A new international project to evaluate the relevance for human systemic and local toxicity of in vitro tests of general toxicity of chemicals has been organized by the Scandinavian Society of Cell Toxicology under the title Multicenter Evaluation of In Vitro Cytotoxicity (MEIC). The basic assumptions underlying the project, as well as the practical goals and the design of the program are outlined. The list of the first 50 reference chemicals is presented. The chemicals are an otherwise unbiased selection of compounds with known human acutely lethal dosage and blood concentrations, including LD50-values in the rat or mouse. Most agents also have other data on human toxicity and toxicokinetics, including more extensive animal toxicity data. International laboratories already using or developing in vitro tests of various partial aspects of general toxicity are invited to test the substances, the results of which will be evaluated by us. The predictivity of the in vitro results for both partial and gross human toxicity data will be determined with combined use of univariate regression analysis and soft multivariate modeling. The predictivity of the in vitro results will be compared with the predictivity of conventional animal tests for the same chemicals. Finally, batteries of tests with optimal prediction power for various types of human toxicity will be selected. The need for and possible uses of such batteries are discussed.

A multivariate approach to saccharide quantitative structure-activity relationships exemplified by two series of 9-hydroxyellipticine glycosides.

Multivariate saccharide quantitative structure-activity relationships (QSARs) have been developed for two series of 9-hydroxyellipticine glycosides. In order to describe the structural variation of the glycoside moieties, thirteen chromatographic variables were used. Eleven D-glycosides and seven L-glycosides were used in separate QSARs to model 9-hydroxyellipticine glycoside antitumour activity against L 1210 leukemia. The multivariate partial least squares (PLS) method was used to establish the QSARs.

[Alpine skiing--a hand injury despite safety hand grips]. / Alpint skiløb--håndskade trods sikkerhedsgreb.

During a fall, a skier sustained two fractures of the metacarpal bones despite special safety hand grips on the ski-sticks. Altered design of these grips is recommended as a prophylactic measure.

Peptide quantitative structure-activity relationships, a multivariate approach.

The variation in amino acid sequence within sets of peptides is described by three principal properties, z1, z2, and z3, per varied amino acid position. These principal properties are derived from a principal components analysis of a matrix of 29 physicochemical variables for the 20 coded (in mRNA) amino acids. The scales z1, z2, and z3 are used to construct informative sets of analogues for exploring and developing quantitative structure-activity relationships (QSAR) of peptides. For the QSARs, the multivariate partial least squares (PLS) method is used. Multivariate QSARs are developed for four families of peptides, and it is shown how these QSARs can predict the activity of new peptide analogues.

Gait with light and heavy fracture bandages on the lower leg.

Using an instrumented treadmill which measured ground reaction forces, ten normal subjects were tested wearing conventional plaster-of-Paris bandages on the lower leg and lightweight crus-plastic bandages. Two different types of heels were also tested. From calculation of gait parameters it was found that the free walking speed was lowest with a conventional bandage with heel. The external work of gait was lowest with the lightweight bandage. Ataxia was least while wearing the lightweight bandage. The lightweight bandage is preferable from a biomechanical point of view, in accordance with the opinion of the subjects.

Relationships between induction of anesthesia and mitotic spindle disturbances studied by means of principal component analysis.

A dataset comprising the activity of 30 compounds in 4 biological tests--anesthesia of tadpoles, anesthesia of frog heart, abnormal growth and spindle disturbances in Allium root tips--was re-evaluated by means of principal component analysis. A two-component model is required to explain the variation in biological activity of the compounds. It is found that abnormal growth is different from the other biological responses. When this test is excluded, as much as 90% of the variation is explained by a one-component model, the determining factor most probably being the lipophilic character of the compounds. Mammalian mitotic cells respond in a similar way to mitotic cells of Allium root tips. It is suggested that possible regularities in the dose-response relationships for anesthesia, teratogenic effects and generation of abnormal chromosome numbers require further exploration.

The prediction of bradykinin potentiating potency of pentapeptides. An example of a peptide quantitative structure-activity relationship.

The variation in amino acid sequence, in a set of bradykinin potentiating pentapeptides, is described by three variables per amino acid position. The variables were derived from a principal components analysis of a property matrix for the 20 coded amino acids. The resulting structure descriptor matrix describes the observed activity of the peptides to 97% by means of a multivariate partial least squares (PLS) model. It is demonstrated that this quantitative structure-activity relationship (QSAR) can be used to predict the activity of new peptide analogs.