Towards the routine use of brain imaging to aid the clinical diagnosis of disorders of consciousness.

Clinical audits have highlighted the many challenges and dilemmas faced by clinicians assessing persons with disorders of consciousness (vegetative state and minimally conscious state). The diagnostic decision-making process is highly subjective, dependent upon the skills of the examiner and invariably dictated by the patients' ability to move or speak. Whilst a considerable amount has been learnt since Jennett and Plum coined the term 'vegetative state', the assessment process remains largely unchanged; conducted at the bedside, using behavioural assessment tools, which are susceptible to environmental and physiological factors. This has created a situation where the rate of misdiagnosis is unacceptably high (up to 43%). In order to address these problems, various functional brain imaging paradigms, which do not rely upon the patient's ability to move or speak, have been proposed as a source of additional information to inform the diagnostic decision making process. Although accumulated evidence from brain imaging, particularly functional magnetic resonance imaging (fMRI), has been encouraging, the empirical evidence is still based on relatively small numbers of patients. It remains unclear whether brain imaging is capable of informing the diagnosis beyond the behavioural assessment and whether brain imaging has any prognostic utility. In this study, we describe the functional brain imaging findings from a group of 41 patients with disorders of consciousness, who undertook a hierarchical speech processing task. We found, contrary to the clinical impression of a specialist team using behavioural assessment tools, that two patients referred to the study with a diagnosis of vegetative state did in fact demonstrate neural correlates of speech comprehension when assessed using functional brain imaging. These fMRI findings were found to have no association with the patient's behavioural presentation at the time of investigation and thus provided additional diagnostic information beyond the traditional clinical assessment. Notably, the utility of brain imaging was further underlined by the finding that the level of auditory processing revealed by functional brain imaging, correlated strongly (rs = 0.81, P < 0.001) with the patient's subsequent behavioural recovery, 6 months after the scan, suggesting that brain imaging may also provide valuable prognostic information. Although further evidence is required before consensus statements can be made regarding the use of brain imaging in clinical decision making for disorders of consciousness, the results from this study clearly highlight the potential of imaging to inform the diagnostic decision-making process for persons with disorders of consciousness.

Structural changes in lysosomes from cultured human fibroblasts in Duchenne's muscular dystrophy.

We have previously reported a decreased activity of the lysosomal enzyme dipeptidyl aminopeptidase-I (DAP-I) in cultured fibroblasts from patients with Duchenne's muscular dystrophy (DMD). Here we report that electron microscope examination of these cells reveals the presence of abundant lamellar bodies, a morphologic abnormalities commonly associated with impaired lysosomal function. Morphometric analysis of these cytoplasmic figures in dystrophic cells shows a sevenfold increase relative to normal controls (P less than 0.01). Analysis of lysosomal density profiles by density gradient centrifugation reveals similar patterns in normal and DMD cells. Treatment of lysosomes wit the nonionic detergent Triton X-100 causes an activation of DAP-I. This activation, attributable to structure-linked latency, is markedly diminished in DMD cells which show an optimal activation of only 180% compared to 255% for control fibroblasts (P less than 0.01). These data suggest an alteration in the properties of the lysosomal membrane in DMD fibroblasts. This suggestion is also supported by studies on the release of DAP-I from lysosomes by osmotic shock which show it to be a membrane-associated enzyme with membrane-binding characteristics intermediate between those of tightly bound beta-glucosidase and those of unbound N-acetylgalactosaminidase. The latency characteristics of these other lysosomal enzymes are not altered in the DMD cells, indicating that the effect is specific for DAP-I.

Consultants in Scotland: survey of educational qualifications, experience and needs of Scottish consultants.

AIMS: To survey Scotland's NHS consultants regarding their teaching roles; educational qualifications/training; attitudes to educational qualifications; perceptions of health boards' attitudes to educational activities; usefulness of various educational courses and preferred delivery methods. METHODS: Postal questionnaire (n=3615). RESULTS: Sixty two percent response rate (n=2246). 98% had one or more roles in education/training. 54% spent more time in educational roles than job-plan allocations. 6% had educational qualifications. 30% rated educational qualifications valuable to their educational role; 21% to their career. 48% had not attended any educational training. 19% of respondents rated their health board as supportive of their educational activities. Respondents rated dealing with underperforming students (74%), dealing with challenging behaviour (63%), appraising students (63%), trainee assessment (61%) and feedback (58%) as the most useful topics. CONCLUSIONS: Scottish consultant involvement in educational activities is virtually universal but consultants perceive they need more time than allocated in job plans. Most consultants had no teaching qualifications. Nearly half had no formal training for educational activities. Educational qualifications were valued by a minority regarding both career development and educational activities. Increased access to staff development for teaching is required as NHS sources are not meeting the need for teacher training of consultant staff.

Decreased lysosomal dipeptidyl aminopeptidase I activity in cultured human skin fibroblasts in Duchenne's muscular dystrophy.

Several lysosomal enzymes were assayed in cultured human skin fibroblasts from patients with Duchenne's muscular dystrophy (DMD) and age- and sex-matched control patients (N). The activity of four glycosidases, cathepsin B(1), and total autoproteolysis at pH 4.0 were unchanged between the groups, but dipeptidyl aminopeptidase I (DAP-I, or cathepsin C) in the DMD cells was found to be only 30% as active as in the control cells (P < 0.003). This difference is not the result of a redistribution or loss of enzyme during homogenization because the difference occurs in all homogenate fractions. DAP-I activity existing in N and DMD fibroblasts behaves identically with respect to activation by chloride ion, activation by the sulfhydryl reducing agent dithiothreitol, changes in hydrogen ion concentration (pH), changes in substrate concentration (i.e., apparent K(m) values), and changes in temperature (i.e., apparent activation energies). Mixtures of N and DMD cell sonicates display an additivity in DAP-I activity. These results support the conclusion that the catalytic function of the DAP-I molecule is equivalent between N and DMD fibroblasts, and that the decrease in tissue-specific DAP-I activity probably results from the fact that fewer enzyme molecules are present in the DMD cells. These results are also an indication that these nonmuscle cells are expressing some of the phenotypic aspects of the genetic defect in DMD. Cultured human skin fibroblasts may therefore be a useful cellular model in DMD research.

Decreased structure-linked latency of lysosomal dipeptidyl aminopeptidase-I activity in Duchenne muscular dystrophy fibroblasts.

Crude lysosomal pellets were prepared from skin fibroblasts grown from patients having Duchenne muscular dystrophy, and from normal controls. Disruption of the lysosomes by nonionic detergents resulted in the expression of latent activity of the enzyme dipeptidyl aminopeptidase-I(DAP-I). Duchenne lysosomes showed less structure-linked latency than those from normal controls, and sedimentation studies demonstrated that the difference was not caused by increased leakage of the enzyme from lysosomes. Permeability properties of the lysosomes for an artificial substrate revealed no difference of the apparent Km. However, in intact lysosomes the apparent K, for Cl- of this chloride-requiring enzyme was found to be lower in DMD lysosomes. The apparent increase in entry for Cl- was closely related with the decreased amount of the DAP-I latency. High concentrations of extra-lysosomal Cl- corrected the abnormality.

Identification of a biochemical difference between male and female human fibroblasts: implications for the expression of Duchenne muscular dystrophy.

The lysosomal enzyme dipeptidyl aminopeptidase-I (DAP-I) was reduced in Duchenne muscular dystrophy (DMD) fibroblasts to 30% of the level found in age- and sex-matched controls (p less than 0.005). Structure-linked latency, defined as the increase in DAP-I activity caused by disruption of the lysosomal membrane, was also reduced in Duchenne fibroblasts to 70% of normal levels (p less than 0.001). Duchenne carriers and age- and sex-matched control fibroblasts had similar DAP-I activities and latency. However, the similarity of normal and carrier female DAP-I activities was not due to elevation of the carrier female activities to levels similar to normal males, but rather to reduction of all female DAP-I activities to 30% of normal male levels (p less than 0.001). This gave them comparable activities to those of the male DMD cells. One explanation for these unexpected results would require a modification of the genetics of DMD to that of a Y-influenced X-linked model.

Intrinsic left ventricular contractility in normal subjects.

The influence of autonomic tone on left ventricular (LV) contractility, along with the range of normal values and the effects of exercise on contractile state, were studied in 12 normal volunteers. Serial reproducibility was examined in a subgroup of 6. LV contractility was estimated by the LV peak-systolic pressure to end-systolic volume relation (pressure-volume relation), and the ratio of peak-systolic pressure to end-systolic volume (pressure/volume ratio). The cuff blood pressure and radionuclide ventriculogram were recorded at rest, during exercise and during pharmacologic pressure-afterloading with phenylephrine, before and after vagal and beta-adrenergic "blockade." Both the pressure/volume ratio and ejection fraction increased during the stimulus of exercise (both p less than or equal to 0.008). After blockade, the pressure-volume relations were highly linear (r = 0.95 +/- 0.05 [standard deviation], n = 12), and there was no systematic difference in their slopes induced by blockade. The serial studies of pressure-volume relations showed no significant differences. The results demonstrated that vagal and sympathetic tone were not important in the support of LV contractility in normal subjects at rest, and that the pressure-volume relation and pressure/volume ratio are reproducible between studies. Also, the findings confirmed that both the pressure/volume ratio and the ejection fraction were sensitive to exercise-induced changes in contractility. This demonstration of intrinsic LV contractility in normal subjects, plus the reproducibility of the measurements, supports the feasibility of serial study of LV contractility.

Precordial auscultatory findings in pneumoperitoneum.

A case is reported of a patient in whom a loud precordial click developed postoperatively. The new sound was attributed to pneumoperitoneum. A series of 17 patients is presented who underwent elective surgical procedures that produce pneumoperitoneum. Postoperative precordial auscultation revealed abnormalities in nine which included sounds mimicking clicks or gallops and changes in intensity of previously normal heart sounds. Thus, pneumoperitoneum can produce abnormal precordial auscultatory findings.

Three decades of Medicare: what the numbers tell us.

The Medicare program was first implemented to meet a critical need in American society, and over its thirty-year history it has evolved into an integral part of the U.S. health care system. This DataWatch provides a broad overview of the program, outlining both historical and current trends in coverage, financing, payment mechanisms, beneficiary status, benefits, and spending.

Utilizing cognitive therapy on the short-term psychiatric inpatient unit.

Cognitive therapy as applied to the short-term psychiatric inpatient unit is explored. The authors provide an overview of the cognitive model and the utilization of cognitive-behavioral therapies for a variety of diagnostic categories. Adaptations of cognitive techniques to the inpatient unit are described and illustrated through case presentations.

Electroconvulsive therapy in the very old.

At least one study has questioned the safety of electroconvulsive therapy (ECT) in the very old. In this study, the authors reviewed a 5-year experience with ECT at two university psychiatric services for patients 75 years of age or older. Both outcomes and complications were reviewed. Nineteen of 22 patients (86.3%) were ECT responders. Five patients (22.7%) suffered complications which varied from minor to substantial. ECT was found to be an effective and reasonably safe treatment for depression in the very old.

Emotional adjustment to cardiac transplantation.

Emotional adjustment to cardiac transplantation is a phasic process. Each step is associated with a milestone in the transplantation protocol. The adjustment process is divided into seven distinct stages: 1) transplant proposal, 2) evaluation, 3) awaiting a donor organ, 4) perioperative period, 5) inhospital convalescence, 6) discharge, and 7) post-discharge adaptation. Patient adjustment to transplantation is influenced by the adaptive task of each stage in the procedure, personality factors, previous experience with illness, and social support. Patients need time to adjust to each stage. Do not pressure them into premature acceptance of transplantation. Verbalization of feelings should be encouraged, and adequate support ensured. Contact with already transplanted patients is helpful to surgical candidates. Psychiatric assistance can greatly aid in patient management and emotional adjustment.

Assessment of left ventricular ejection fraction from technetium-99m-methoxy isobutyl isonitrile multiple-gated radionuclide angiocardiography.

Abnormal left ventricular function is a diagnostic indication of cardiac disease. Left ventricular function is commonly quantified by ejection fraction measurements. A novel approach for the determination of left ventricular ejection fraction from technetium-99m-methoxy isobutyl isonitrile multiple-gated radionuclide angiocardiography is presented. Data from 23 patients, symptomatic of cardiac disease, indicate that ejection fractions determined using the radionuclide technique correlate well with contrast X-ray single-plane cineangiography (r=0.83, p<10(-6)). Data from 14 of the patients indicate favorable correlation with technetium-99m-pertechnetate gated blood pool radionuclide angiocardiography (r=0.87, p<10(-4)).

A physics-based coordinate transformation for 3-D image matching.

Many image matching schemes are based on mapping coordinate locations, such as the locations of landmarks, in one image to corresponding locations in a second image. A new approach to this mapping (coordinate transformation), called the elastic body spline (EBS), is described. The spline is based on a physical model of a homogeneous, isotropic three-dimensional (3-D) elastic body. The model can approximate the way that some physical objects deform. The EBS as well as the affine transformation, the thin plate spline [1], [2] and the volume spline [3] are used to match 3-D magnetic resonance images (MRI's) of the breast that are used in the diagnosis and evaluation of breast cancer. These coordinate transformations are evaluated with different types of deformations and different numbers of corresponding (paired) coordinate locations. In all but one of the cases considered, using the EBS yields more similar images than the other methods.

Adolescent self-disclosure and loneliness: private self-consciousness and parental influences.

Using structural equation techniques, we tested a theoretical model designed to describe the causal relations existing among loneliness, self-disclosure to peers and parents, and specific antecedent variables. Participants were 350 high-school students who answered questions concerning themselves and their interpersonal relationships. Results generally indicated a good fit between the theoretical model and the observed relations. In addition to replicating the findings of previous studies concerning the relation between self-disclosure and loneliness, results also indicated an indirect relation between private self-consciousness and loneliness via peer self-disclosure; that is, high private self-conscious adolescents' greater willingness to self-disclose to peers resulted in their feeling less lonely. Results are discussed in terms of current theory in related fields.

Adolescent loneliness, self-disclosure, and private self-consciousness: a longitudinal investigation.

This study builds on an earlier investigation of the causal relations that exist among loneliness, self-disclosure, and private self-consciousness (Franzoi & Davis, 1985). Using structural equation techniques and a longitudinal (Year 1-Year 2) design, the present investigation tested a theoretical model that links these variables. Participants were 406 high school students. As in the previous study, results generally indicated a good fit between the theoretical model and the observed relations. In particular, however, this investigation provided new evidence concerning two alternative interpretations of the original Franzoi and Davis study. First, this study supports the original hypothesis that private self-consciousness leads to greater self-disclosure to peers, but it offers no support for the alternative view that such disclosure in turn increases private self-consciousness. Second, this investigation is somewhat equivocal with respect to the original hypothesis that greater self-disclosure reduces loneliness. Both this hypothesis and the alternative view that greater loneliness reduces self-disclosure, receive some support from the data in this study. Finally, the difficulty in obtaining significant longitudinal paths (from Year 1 to Year 2) suggests that the time lags in the variables' effects on one another are relatively short rather than long.

The effects of private self-consciousness and perspective taking on satisfaction in close relationships.

We extended the scope of recent studies in which self-awareness and perspective taking have been used as predictors of social competence or adjustment: We analyzed their influence on the satisfaction experienced in monogamous, heterosexual relationships. Members of 131 couples answered questions concerning themselves and their relationships. We predicted that individual differences in private self-consciousness would be positively related to relationship satisfaction because of the greater self-disclosure resulting from that heightened self-attention. Second, we predicted that individual differences in perspective taking would foster relationship satisfaction, independent of any influence of self-disclosure. Both expectations were confirmed. Scores on the private self-consciousness scale were predictive of reported self-disclosure, and self-disclosure was predictive of satisfaction in the relationship. Furthermore, once the influence of self-disclosure was removed, no effect of self-consciousness on satisfaction remained. In contrast, after disclosure was controlled, perspective-taking scores were significantly related to satisfaction and were in fact unrelated to disclosure at all. These findings indicate that two personality characteristics having to do with habitual attention to behavioral tendencies, to emotions, and to motivations significantly enhance the quality of close heterosexual relationships in different ways. Results are discussed in terms of current theory in the related fields.

Two social worlds: social correlates and stability of adolescent status groups.

Adolescents' peer group status in high school was examined using self-report, peer nominations, and archival data collected during 2 consecutive school years. Higher status students (popular and controversial) had more close friends, engaged more frequently in peer activities, and self-disclosed more than lower status students (rejected and neglected). They were also more involved in extracurricular school activities and received more social honors from their schoolmates. Although the higher status students were more alike than different, controversial adolescents did report more self-disclosure and dating behavior than popular students. Lower status students were also highly similar, although rejected students reported lower grades. Regarding the temporal stability of these status groups, the adolescent sample exhibited slightly higher overall stability than that found in previous investigations of younger children.

Effect of perspective taking on the cognitive representation of persons: a merging of self and other.

Two experiments examined the possibility that perspective taking leads observers to create cognitive representation of others that substantially overlap with the observers' own self-representations. In Experiment 1 observers receiving role-taking instructions were more likely to ascribe traits to a novel target that they (observers) had earlier indicated were self-descriptive. This pattern was most pronounced, however for positively valenced traits. In Experiment 2 some participants received role-taking instructions but were also given a distracting memory task. In the absence of this task, role taking again produced greater overlap--primarily for positive traits--between self- and target representations. In the presence of the memory task, the degree of self-target overlap was significantly reduced for all traits, regardless of valence. Possible explanations for these findings are discussed.

Relationship-specific and global perceptions of social support: associations with well-being and attachment.

Is one's global sense of social support largely a summation of the support perceived to exist within current social relationships, or is it a trait-like construct independent of current support levels? To address this issue, 183 college students completed measures of global support, support from four different social domains, attachment style, and several measures of well-being. Hierarchical regression analyses revealed that for two well-being measures (global and social loneliness), both global and domain support displayed significant unique associations; for emotional loneliness, only domain support had a significant unique influence. For the well-being measure reflecting generalized negative affect, only global support displayed such a unique association. Thus, global and domain support appear to be, to a considerable degree, independent constructs, each with its own sphere of influence in affecting well-being.