Essential role for Atox1 in the copper-mediated intracellular trafficking of the Menkes ATPase

The metallochaperone Atox1 directly interacts with the copper-transporting ATPases and plays a critical role in perinatal copper homeostasis. To determine the cell biological mechanisms of Atox1 function, intracellular copper metabolism, and Menkes ATPase abundance, localization and trafficking were examined in immortalized fibroblast cell lines derived from Atox1(+/+) and Atox1(-/-) embryos. Consistent with the proposed role for Atox1 in copper delivery to the secretory pathway, a marked increase in intracellular copper content secondary to impaired copper efflux was observed in Atox1-deficient cells. Although the localization of the Menkes ATPase was identical in Atox1(+/+) and Atox1(-/-) cells under conditions of equivalent intracellular copper content, a significant impairment in copper-mediated Menkes ATPase trafficking was observed in the absence of Atox1. When quantitative confocal immunofluorescence was used, significant differences in the time and dose-dependent trafficking of the Menkes ATPase from the Golgi compartment in response to copper were observed between Atox1(+/+) and Atox1(-/-) cells. These data reveal an essential role for Atox1 in establishing the threshold for copper-dependent movement of the copper-transporting ATPases within the secretory compartment and that, in the absence of Atox1, this movement alone is not sufficient to restore normal copper efflux. Taken together, these findings provide a cell biological model for the role of this metallochaperone under the physiological conditions of copper limitation in mammalian cells.     

Peripheral thyroid hormones and response to selective serotonin reuptake inhibitors

OBJECTIVE: To examine the relation between baseline measurements of thyroid function and response to selective serotonin reuptake inhibitors (SSRIs) and to consider the effect of these antidepressants on thyroid hormone levels. METHODS: Nineteen subjects with major depression, but without a history of thyroid treatment or lithium treatment, were treated openly with either sertraline or fluoxetine in a university- affiliated tertiary care hospital. Hamilton Depression Rating Scale (Ham-D) scores were measured before and after treatment. Clinical Global Impressions (CGI) scores were measured at study end. Thyroid data, consisting of values for thyroid-stimulating hormone (TSH), triiodothyronine (T(3), measured by radioimmunoassay [RIA]), thyroxine (T(4), measured by RIA) and free T(4), were collected before and after treatment. Complete thyroid data were available for 17 subjects. Data were collected during 1997-1999. RESULTS: Baseline TSH correlated strongly with response to treatment as measured by change in Ham-D scores (r = 0.64, p = 0.003). Low TSH values correlated with greater improvement in depressive symptoms. Thyroid hormone levels decreased with treatment, but these decreases did not correlate with clinical improvement. CONCLUSION: Baseline thyroid function, as measured by serum TSH, may predict a patient's response to antidepressant treatment with SSRIs. Optimal thyroid function, beyond simply being within the normal laboratory values, may be necessary for an optimal response to antidepressants.     

Well-being, appraisal, and coping in African-American and Caucasian dementia caregivers: findings from the REACH study

Although there has been considerable interest in racial differences in family caregiving for persons with dementia, most research to date has either ignored racial diversity or based conclusions on small numbers of caregivers drawn primarily from single site studies. The current study utilized participants from four sites of the REACH (Resources for Enhancing Alzheimer's Caregiver Health) multi-site study to compare well-being, appraisal, and religious coping by race. African-American (n = 295) and Caucasian (n = 425) dementia caregivers from four cities (Birmingham, Memphis, Boston, and Philadelphia) were compared in their demographics, care recipient characteristics, mental and physical health, and psychosocial coping resources including appraisal and religious coping. African-American caregivers reported lower anxiety, better well-being, less use of psychotropic medications, more benign appraisals of stress and perceived benefits of caregiving, and greater religious coping and participation, than Caucasian caregivers. Self-rated health did not differ by race, but African-American caregivers reported more unhealthy behaviors than Caucasian caregivers. Some results were specific to site, possibly due to differences in recruitment strategies, inclusion/exclusion criteria, and regional differences. Adjustment for covariates, including caregiver relationship to the care recipient, gender, age, socioeconomic status, and care recipient behavioral problems, altered few of these differences. Results are discussed in terms of their relevance to psychosocial intervention programs for ethnically diverse caregivers.     

The Caregiver Vigilance Scale: application and validation in the Resources for Enhancing Alzheimer's Caregiver Health (REACH) project

This article reports on the measurement properties of Caregiver Vigilance, a four-item caregiver self-report of perceived oversight demand for Alzheimer's disease and related disorders family caregiving. The self-report uses data from the Resources for Enhancing Alzheimer's Caregiver Health (REACH) project, a multisite National Institutes of Health (NIH) sponsored study of over 1,200 family caregivers. Results indicate that the items were clearly understood by the racially/ethnically diverse respondents; and, when responses were transformed into a summary scale and analyzed, unidimensionality was evident and internal consistency reliability favorably demonstrated. We suggest using the Caregiver Vigilance Scale in conjunction with traditional burden measures to systematically include the caregiving time associated with protectively watching over care recipients and the daily duration of this responsibility. We also highlight the practical utility of selected items for potential use in the caregiver assessment process.     

The role of acute decompression and restoration of spinal alignment in the prevention of post-traumatic syringomyelia: case report and review of recent literature

STUDY DESIGN: Case report. INTRODUCTION: Acute post-traumatic syringomyelia formation after spinal cord injury has been considered a rare complication. At this writing, most recent reports have surfaced in neurosurgical journals. As an entity, post-traumatic syringomyelia has not been widely appreciated. It has been confused with conditions such as Hansen's disease or ulnar nerve compression at the cubital tunnel. One study also demonstrated that the occurrence of syrinx is significantly correlated with spinal stenosis after treatment, and that an inadequate reduction of the spine may lead to the formation of syrinx. This reported case describes a patient in whom post-traumatic syringomyelia began to develop 3 weeks after injury, which improved neurologically after adequate decompression. SUMMARY OF BACKGROUND DATA: A 30-year-old man sustained a 20-foot fall at work. He presented with a complete spinal cord injury below T4 secondary to a T4 fracture dislocation. The patient underwent open reduction and internal fixation of T1-T8. After 3 weeks, the patient was noted to have ascending weakness in his bilateral upper extremities and some clawing of both hands. METHODS: A computed tomography myelogram demonstrated inability of contrast to pass through the T4-T5 region from a lumbar puncture. An incomplete reduction was noted. The canal showed significant stenosis. A magnetic resonance image of the patient's C-spine showed increased signal in the substance of the cord extending into the C1-C2 area. The patient returned to the operating room for T3-T5 decompressive laminectomy and posterolateral decompression including the pedicles, disc, and posterior aspect of the body. Intraoperative ultrasound monitoring showed a good flow of cerebrospinal fluid past the injured segment. RESULTS: On postoperative day 1, the clawing posture of the patient's hands was significantly diminished, and the patient noted an immediate improvement in his hand and arm strength. Over the next few days, the patient's strength in the bilateral upper extremities increased to motor Grade 4/5 on manual testing. A magnetic resonance image 4 weeks after decompression showed significant improvement in the cord diameter and signal. CONCLUSIONS: Post-traumatic syringomyelia has not been reported at so early a stage after injury. This disorder is an important clinical entity that must be recognized to prevent potentially fatal or devastating complications. As evidenced by the reported patient and the literature, if this disorder is discovered and treated early, permanent deficit can be avoided. The prevention of post-traumatic syringomyelia requires anatomic realignment and stabilization of the spine without stenosis, even in the case of complete injuries, to maintain the proper dynamics of cerebrospinal fluid flow.     

Interpretation of Emergency Department radiographs: a comparison of emergency medicine physicians with radiologists, residents with faculty, and film with digital display

OBJECTIVE: We determined the relative value of teleradiology and radiology resident coverage of the emergency department by measuring and comparing the effects of physician specialty, training level, and image display method on accuracy of radiograph interpretation. MATERIALS AND METHODS: A sample of four faculty emergency medicine physicians, four emergency medicine residents, four faculty radiologists, and four radiology residents participated in our study. Each physician interpreted 120 radiographs, approximately half containing a clinically important index finding. Radiographs were interpreted using the original films and high-resolution digital monitors. Accuracy of radiograph interpretation was measured as the area under the physicians' receiver operating characteristic (ROC) curves. RESULTS: The area under the ROC curve was 0.15 (95% confidence interval [CI], 0.10-0.20) greater for radiologists than for emergency medicine physicians, 0.07 (95% CI, 0.02-0.12) greater for faculty than for residents, and 0.07 (95% CI, 0.02-0.12) greater for films than for video monitors. Using these results, we estimated that teleradiology coverage by faculty radiologists would add 0.09 (95% CI, 0.03-0.15) to the area under the ROC curve for radiograph interpretation by emergency medicine faculty alone, and radiology resident coverage would add 0.08 (95% CI, 0.02-0.14) to this area. CONCLUSION: We observed significant differences between the interpretation of radiographs on film and on digital monitors. However, we observed differences of equal or greater magnitude associated with the training level and physician specialty of each observer. In evaluating teleradiology services, observer characteristics must be considered in addition to the quality of image display.     

Subsyndromal depression is associated with functional impairment in patients with bipolar disorder

BACKGROUND: The purpose of this study was to assess whether a relationship exists between mild depressive symptoms and overall functioning in subjects with bipolar disorder. METHOD: Twenty-five male subjects with bipolar I disorder (DSM-III-R criteria), who had not experienced a DSM-III-R episode of mania, hypomania, or major depression for 3 months as determined using the Structured Clinical Interview for DSM-III-R, were evaluated for degree of depressive symptoms using the Hamilton Rating Scale for Depression (HAM-D) and for overall functional status using the Global Assessment of Functioning (GAF, DSM-IV Axis V). RESULTS: GAF scores were significantly negatively correlated with HAM-D scores (r = -0.61, df = 23, p = .001), despite the fact that no patient had a HAM-D score high enough to be considered clinically depressed. CONCLUSION: The results of this study support a relationship between subsyndromal depressive symptoms and functional impairment in bipolar subjects, despite their not meeting threshold criteria for a major depressive episode. These findings raise the possibility that in some patients with bipolar disorder subsyndromal depressive symptoms might contribute to ongoing functional impairment.