Discriminating Between Individuals with and without Musculoskeletal Disorders of the Upper Extremity by Means of Items Related to Computer Keyboard Use

INTRODUCTION: Identifying postures and behaviors during keyboard use that can discriminate between individuals with and without musculoskeletal disorders of the upper extremity (MSD-UE) is important for developing intervention strategies. This study explores the ability of models built from items of the Keyboard-Personal Computer Style instrument (K-PeCS) to discriminate between subjects who have MSD-UE and those who do not. METHODS: Forty-two subjects, 21 with diagnosed MSD-UE (cases) and 21 without MSD-UE (controls), were videotaped while using their keyboards at their onsite computer workstations. These video clips were rated using the K-PeCS. The K-PeCS items were used to generate models to discriminate between cases and controls using Classification and Regression Tree (CART) methods. RESULTS: Two CART models were generated; one that could accurately discriminate between cases and controls when the cases had any diagnosis of MSD-UE (69% accuracy) and one that could accurately discriminate between cases and controls when the cases had neck-related MSD-UE (93% accuracy). Both models had the same single item, "neck flexion angle greater than 20 degrees ". In both models, subjects who did not have a neck flexion angle of greater than 20 degrees were accurately identified as controls. CONCLUSIONS: The K-PeCS item "neck flexion greater than 20 degrees " can discriminate between subjects with and without MSD-UE. Further research with a larger sample is needed to develop models that have greater accuracy.     

Association between esophageal dysmotility and gastroesophaeal reflux on barium studies

OBJECTIVE: To determine whether there is an association between abnormal primary peristalsis in the esophagus and gastroesophageal reflux (GER) on barium studies. METHODS: A computerized search of radiologic reports revealed 151 patients with esophageal dysmotility (characterized by intermittently decreased or absent peristalsis in the esophagus on upper gastrointestinal tract examinations) who fulfilled our study's entry criteria. These 151 patients were stratified into two groups depending on whether this dysmotility was associated with nonperistaltic contractions (NPCs): 92 patients had no NPCs (Dysmotility and No NPCs Group) and 59 had NPCs (Dysmotility and NPCs Group). An age-matched control group of 92 patients with normal motility was also generated from the radiologic reports. The reports were also reviewed for the presence and degree of GER and other complications of GER. The frequency and degree of GER were tabulated for each group, and the data were analyzed using a Pearson chi square test to determine if significant differences were present in the frequency and degree of GER or other findings among the groups. RESULTS: The frequency of GER was significantly higher in patients with abnormal peristalsis and no NPCs than in controls (p = 0.02). When GER was stratified based on the degree of reflux, the frequency of moderate-to-marked GER was significantly higher in patients with abnormal peristalsis and no NPCs than in patients with abnormal peristalsis and NPCs (p = 0.01) or in controls (p = 0.0031). The frequency of reflux esophagitis also was significantly higher in patients with abnormal peristalsis and no NPCs than in controls (p = 0.04). CONCLUSION: Our findings suggest that patients with esophageal dysmotility characterized by intermittently decreased or absent peristalsis without NPCs have a significantly higher frequency and degree of GER than patients with normal motility. The presence of this specific form of esophageal dysmotility on barium studies therefore should suggest underlying reflux disease.     

Reciprocal influence of concurrent walking and cognitive testing on performance in older adults

This study investigated how cognitive and walking performance are influenced when performed concurrently in older adults and what factors are associated with poorer dual-task responses. Using a dual-task study design, 217 subjects aged 74-85 years completed three information processing test conditions--(1) no test; (2) push-button simple reaction-time; and (3) visual-spatial decision reaction-time; and three walking test conditions--(1) seated; (2) walking over a 20m straight course; and (3) walking over 20m with a turn. Push-button and visual-spatial reaction-times increased approximately 21% and 6%, respectively, while walking compared to sitting (p<0.008). Reaction-time tests had a relatively weak impact on walking-time. Poorer dual-task walking-time responses correlated with slower walking velocity and weaker muscle strength (p< or =.062). Findings suggest that walking requires significant cognitive resources among older adults and slower-walking adults and weaker adults may require higher cognitive loading while walking.     

Gastroesophageal reflux: comparison of barium studies with 24-h pH monitoring

OBJECTIVE: To determine the correlation between massive gastroesophageal reflux (GER) on barium studies and pathologic acid reflux on 24-h pH monitoring. METHODS: A search of hospital records from January 1997 to January 2001 revealed 28 patients who underwent both barium studies and 24-h pH monitoring. The radiologic reports were reviewed to determine the presence and degree of GER. Patients with reflux to or above the thoracic inlet either spontaneously or with provocative maneuvers in the recumbent position were classified as having massive reflux, whereas the remaining patients with reflux below the thoracic inlet or no reflux comprised the control group. The pH monitoring reports were also reviewed to determine if pathologic acid reflux was present in the recumbent position. The findings on these studies were then compared to determine the frequency of pathologic acid reflux in the recumbent position on pH monitoring in patients with massive reflux on barium studies compared with the control group. RESULTS: Massive GER was observed on barium studies in 11 (39%) of the 28 patients and reflux below the thoracic inlet or no reflux in the remaining 17 patients (61%) who comprised the control group. All 11 patients (100%) with massive reflux on barium studies had pathologic acid reflux on pH monitoring in the recumbent position compared with six (35%) of 17 patients in the control group (P = 0.0009). The pH in the distal esophagus on pH monitoring was less than 4.0 for 13.1% of the recumbent period for patients with massive GER on barium studies compared with 6.2% of the recumbent period for the control group (P = 0.0076). CONCLUSION: Although 24-h pH monitoring remains the gold standard for the detection of GER, our experience suggests that patients with massive reflux on barium studies are so likely to have pathologic acid reflux in the recumbent position that these individuals can be further evaluated and treated for their gastroesophageal reflux disease (GERD) without need for pH monitoring.     

Influence of isomerisation on the growth inhibitory effects and cellular activity of 13-cis and all-trans retinoic acid in neuroblastoma cells

Treatment with 13-cis retinoic acid (13-cis RA) has been shown to significantly improve the clinical outcome of children with high-risk neuroblastoma. Despite the large number of studies investigating the cellular effects of retinoids in neuroblastoma cells, the influence of RA isomerisation and the factors that determine the extent of RA isomerisation and uptake are unknown. The aim of this study was to establish the extent of extra- and intracellular isomerisation of 13-cis RA and all-trans retinoic acid (ATRA) in neuroblastoma cell lines, and to investigate the influence of isomerisation on their growth inhibitory effects and on the regulation of expression of cellular retinoic acid binding protein II (CRABP II) and RAR-beta. Limited extracellular isomerisation was observed up to 72 hr after incubation of four neuroblastoma cell lines with 10 microM 13-cis RA or ATRA. The retinoic acid isomer present initially in the medium accounted for >75% of extracellular retinoid exposure. By contrast, incubation with 13-cis RA resulted in intracellular levels of ATRA comparable to those of 13-cis RA. This degree of intracellular isomerisation was not observed after ATRA incubations, with 13-cis RA accounting for <10% of total intracellular retinoids. No differences were observed in the sensitivity of three N-type neuroblastoma cell lines to either 13-cis RA (IC(50): 11.2-13.9 microM) or ATRA (IC(50): 12.9-14.4 microM), despite 10-fold differences in intracellular retinoid levels. A decrease in sensitivity to 13-cis RA (IC(50)=137 microM), as compared to ATRA (IC(50)=41 microM), was observed in the S-type cell line SH S EP. RAR-beta was induced in a dose-dependent manner in SH SY 5Y cells following incubation with ATRA, whereas a weaker and delayed induction was observed with 13-cis RA. Similarly, incubation with ATRA resulted in a greater induction of CRABP II in these cells. In summary, these results indicate either an intracellular conversion of 13-cis RA to ATRA or a selective uptake of ATRA and suggest that this may mediate the differential activity of 13-cis RA in neuroblastoma cell subtypes.     

Biomechanics of trailing leg response to slipping - Evidence of interlimb and intralimb coordination

This gait study characterizes the trailing leg's biomechanical response to slips. Twenty-eight healthy participants divided into two age groups (20–33 years and 55–67 years) were asked to walk in two conditions: a known dry floor and a glycerol-contaminated floor expected to be dry, inducing an unexpected slip of the leading foot at heel contact. Four slip-related trailing leg response strategies were identified, ranging from a minimal disruption of the swing phase to a premature (50 ms after toe off) interruption of the swing phase. Aging effects were minimal. The response of the leading/slipping leg preceded that of the trailing limb. The magnitude of the trailing leg's response was associated with that of the knee in the leading/slipping leg, suggesting interlimb coordination. The corrective moment at the knee of the trailing leg was also correlated with that measured at the hip in the same leg, suggesting intralimb coordination. The specific trailing leg's strategy used in a slip is partially determined by pre-slip walking patterns and early stance slip dynamics.     

Increasing melanoma cell death using inhibitors of protein disulfide isomerases to abrogate survival responses to endoplasmic reticulum stress

Exploiting vulnerabilities in the intracellular signaling pathways of tumor cells is a key strategy for the development of new drugs. The activation of cellular stress responses mediated by the endoplasmic reticulum (ER) allows cancer cells to survive outside their normal environment. Many proteins that protect cells against ER stress are active as protein disulfide isomerases (PDI) and the aim of this study was to test the hypothesis that apoptosis in response to ER stress can be increased by inhibiting PDI activity. We show that the novel chemotherapeutic drugs fenretinide and velcade induce ER stress-mediated apoptosis in melanoma cells. Both stress response and apoptosis were enhanced by the PDI inhibitor bacitracin. Overexpression of the main cellular PDI, procollagen-proline, 2-oxoglutarate-4-dioxygenase beta subunit (P4HB), resulted in increased PDI activity and abrogated the apoptosis-enhancing effect of bacitracin. In contrast, overexpression of a mutant P4HB lacking PDI activity did not increase cellular PDI activity or block the effects of bacitracin. These results show that inhibition of PDI activity increases apoptosis in response to agents which induce ER stress and suggest that the development of potent, small-molecule PDI inhibitors has significant potential as a powerful tool for enhancing the efficacy of chemotherapy in melanoma.     

Vestibulo-ocular function in anxiety disorders

Previous studies of vestibulo-ocular function in patients with anxiety disorders have suggested a higher prevalence of peripheral vestibular dysfunction compared to control populations, especially in panic disorder with agoraphobia. Also, our recent companion studies have indicated abnormalities in postural control in patients with anxiety disorders who report a high degree of space and motion discomfort. The aim of the present study was to assess the VOR, including the semicircular canal-ocular reflex, the otolith-ocular reflex, and semicircular canal-otolith interaction, in a well-defined group of patients with anxiety disorders. The study included 72 patients with anxiety disorders (age 30.6 +/- 10.6 yrs; 60 (83.3% F) and 29 psychiatrically normal controls (age 35.0 +/minus; 11.6 yrs; 24 (82.8% F). 25 patients had panic disorder; 47 patients had non-panic anxiety. Patients were further categorized based on the presence (45 of 72) or absence (27 of 72) of height phobia and the presence (27 of 72) or absence (45 of 72) of excessive space and motion discomfort (SMD). Sinusoidal and constant velocity earth-vertical axis rotation (EVAR) was used to assess the semicircular canal-ocular reflex. Constant velocity off-vertical axis rotation (OVAR) was used to assess both the otolith-ocular reflex and static semicircular canal-otolith interaction. Sinusoidal OVAR was used to assess dynamic semicircular canal-otolith interaction. The eye movement response to rotation was measured using bitemporal electro-oculography. Results showed a significantly higher VOR gain and a significantly shorter VOR time constant in anxiety patients. The effect of anxiety on VOR gain was significantly greater in patients without SMD as compared to those with SMD. Anxiety patients without height phobia had a larger OVAR modulation. We postulate that in patients with anxiety, there is increased vestibular sensitivity and impaired velocity storage. Excessive SMD and height phobia seem to have a mitigating effect on abnormal vestibular sensitivity, possibly via a down-weighting of central vestibular pathways.