Independent risk factors of carpal tunnel syndrome: Assessment of body mass index, hand, wrist and finger anthropometric measurements.

BACKGROUND: The most prevalent neuropathy in the upper extremity is carpal tunnel syndrome (CTS). A variety of related risk factors such as biomechanical exposures, body mass index (BMI), sex and hand shape are reported to be related to CTS. OBJECTIVE: We aimed to identify the role of BMI, hand, wrist and finger anthropometric dimensions in the development of CTS, and to compare these measured variables between control and CTS participants. METHODS: A cross-sectional, case control study (n = 240, CTS = 120, controls = 120) with participants recruited from a convenience sample diagnosed with CTS and referred for anthropometric measurements. The control participants were matched by age and sex. The body height, weight, hand width, hand length, wrist depth, wrist width, wrist circumference, and finger length were measured. Hand, wrist and finger indices, hand to height ratio, and BMI were calculated. Mean values of all dimensions were compared between cases and controls, and the role of independent risk factors were determined by logistic regression analysis. RESULTS: The mean BMI, age, weight, sex and height were not significant between the two groups. Among the measured dimensions and calculated indices the significantly different variables between two groups were the wrist width, wrist depth, wrist circumference, hand index, hand to height index, and wrist index. Regression analysis showed that the wrist index (ß=-1.7, p = 0.0001), wrist depth (ß=0.25, p = 0.0001) and wrist width (ß=0.21, p = 0.0001) were the strongest factors in CTS development in the sample. CONCLUSION: Wrist parameters have a strong role in predicting the development of CTS, while BMI was not confirmed as an independent risk factor.

Theoretical and conceptual frameworks across local evaluation efforts in a nationwide consortium.

This paper describes the theoretical and conceptual frameworks used to guide the site-level evaluations of Building Infrastructure Leading to Diversity (BUILD) programs, part of the Diversity Program Consortium (DPC), funded by the National Institutes of Health. We aim to provide an understanding of which theories informed the evaluation work of the DPC and how the frameworks guiding BUILD site-level evaluations are conceptually aligned with one another and with the consortium-level evaluation.

Face Selective Neural Activity: Comparisons Between Fixed and Free Viewing.

Event Related Potentials (ERPs) are widely used to study category-selective EEG responses to visual stimuli, such as the face-selective N170 component. Typically, this is done by flashing stimuli at the point of static gaze fixation. While allowing for good experimental control, these paradigms ignore the dynamic role of eye-movements in natural vision. Fixation-related potentials (FRPs), obtained using simultaneous EEG and eye-tracking, overcome this limitation. Various studies have used FRPs to study processes such as lexical processing, target detection and attention allocation. The goal of this study was to carefully compare face-sensitive activity time-locked to an abrupt stimulus onset at fixation, with that time-locked to a self-generated fixation on a stimulus. Twelve participants participated in three experimental conditions: Free-viewing (FRPs), Cued-viewing (FRPs) and Control (ERPs). We used a multiple regression approach to disentangle overlapping activity components. Our results show that the N170 face-effect is evident for the first fixation on a stimulus, whether it follows a self-generated saccade or stimulus appearance at fixation point. The N170 face-effect has similar topography across viewing conditions, but there were major differences within each stimulus category. We ascribe these differences to an overlap of the fixation-related lambda response and the N170. We tested the plausibility of this account using dipole simulations. Finally, the N170 exhibits category-specific adaptation in free viewing. This study establishes the comparability of the free-viewing N170 face-effect with the classic event-related effect, while highlighting the importance of accounting for eye-movement related effects.

Independently together: subthalamic theta and beta opposite roles in predicting Parkinson's tremor.

Tremor is a core feature of Parkinson's disease and the most easily recognized Parkinsonian sign. Nonetheless, its pathophysiology remains poorly understood. Here, we show that multispectral spiking activity in the posterior-dorso-lateral oscillatory (motor) region of the subthalamic nucleus distinguishes resting tremor from the other Parkinsonian motor signs and strongly correlates with its severity. We evaluated microelectrode-spiking activity from the subthalamic dorsolateral oscillatory region of 70 Parkinson's disease patients who underwent deep brain stimulation surgery (114 subthalamic nuclei, 166 electrode trajectories). We then investigated the relationship between patients' clinical Unified Parkinson's Disease Rating Scale score and their peak theta (4-7 Hz) and beta (13-30 Hz) powers. We found a positive correlation between resting tremor and theta activity (r = 0.41, P < 0.01) and a non-significant negative correlation with beta activity (r = -0.2, P = 0.5). Hypothesizing that the two neuronal frequencies mask each other's relationship with resting tremor, we created a non-linear model of their proportional spectral powers and investigated its relationship with resting tremor. As hypothesized, patients' proportional scores correlated better than either theta or beta alone (r = 0.54, P < 0.001). However, theta and beta oscillations were frequently temporally correlated (38/70 patients manifested significant positive temporal correlations and 1/70 exhibited significant negative correlation between the two frequency bands). When comparing theta and beta temporal relationship (r θ ß) to patients' resting tremor scores, we found a significant negative correlation between the two (r = -0.38, P < 0.01). Patients manifesting a positive correlation between the two bands (i.e. theta and beta were likely to appear simultaneously) were found to have lower resting tremor scores than those with near-zero correlation values (i.e. theta and beta were likely to appear separately). We therefore created a new model incorporating patients' proportional theta-beta power and r θ ßscores to obtain an improved neural correlate of resting tremor (r = 0.62, P < 0.001). We then used the Akaike and Bayesian information criteria for model selection and found the multispectral model, incorporating theta-beta proportional power and their correlation, to be the best fitting model, with 0.96 and 0.89 probabilities, respectively. Here we found that as theta increases, beta decreases and the two appear separately-resting tremor is worsened. Our results therefore show that theta and beta convey information about resting tremor in opposite ways. Furthermore, the finding that theta and beta coactivity is negatively correlated with resting tremor suggests that theta-beta non-linear scale may be a valuable biomarker for Parkinson's resting tremor in future adaptive deep brain stimulation techniques.

Production of ectopic gastric intrinsic factor in gastric mucosa of humans with chronic gastritis.

BACKGROUND: Ectopic expression of gastric intrinsic factor (IF) has been described in rodent models of chronic gastritis. AIMS: The current study undertook to determine if ectopic IF was also present in chronic gastritis in humans and might identify the process of ectopic protein expression as part of the response to chronic injury. METHODS: Archived biopsies from mid-body, angularis and prepylorus of 9 patients with and without chronic gastritis and food-cobalamin malabsorption were examined in a blinded fashion by immunocytochemistry as were biopsies from 5 normal subjects. Cells with ectopic IF were further examined with antibodies against pepsin or with Griffonia simplicifolia II (GSII) to identity cells in the mucous neck cell compartment. RESULTS: Ectopic IF production in non-parietal cells was identified in cells that were H(+),K(+)-ATPase-negative but IF-positive in 7 of the 9 patients (6/9 in the angularis and/or prepylorus biopsies and 1/9 only in the mid-body). These included 5 of the 6 H. pylori-infected patients and all 5 patients with severe food-cobalamin malabsorption. No normal control subjects demonstrated ectopic IF. The cells with ectopic IF were pepsinogen-positive peptic cells and were not GSII-positive. Expression was most extensive in patients and gastric regions with inflammation. In all but one sample, ectopic IF was observed near anatomical mucosal junctions, such as antral/body and prepylorus/duodenum junctions. CONCLUSIONS: These data in humans with and without gastritis are consistent with the hypothesis that local factors influence ectopic gastric IF expression, arising from either the anatomical location, the focal inflammation, or both.

Plasma total transcobalamin I. Ethnic/racial patterns and comparison with lactoferrin.

Plasma total transcobalamin (TC) I levels were measured in 434 healthy volunteers by radioimmunoassay (RIA). The results were analyzed for demographic patterns and were compared with lactoferrin, cobalamin, homocysteine, and chemistry panel results. Plasma TC I was higher in blacks than in other ethnic/racial groups and higher in women than in men. TC I levels did not correlate with lactoferrin levels. Lactoferrin showed significant ethnic differences also, but, unlike TC I, its levels were highest in whites. TC I levels correlated with cobalamin but not homocysteine levels. Neither TC I nor lactoferrin correlated with chemistry panel results, including creatinine, total protein, albumin, lactate dehydrogenase, and alkaline phosphatase levels. The demonstration with an RIA that directly measures total TC I that plasma levels are significantly higher in blacks than in other groups may explain the well-known higher cobalamin levels in blacks. Surprisingly, plasma lactoferrin, which has the same cellular sources as TC I, does not correlate with plasma TC I levels and shows dissimilar demographic patterns; lactoferrin levels are highest in whites. These findings suggest that regulation and/or secretion of these 2 proteins differ even though their localization and expression patterns in myeloid precursors are similar.

Anemia and aging: an overview of clinical, diagnostic and biological issues.

Anemia, usually mild, is one of the more common problems of the aged, especially in men. Although the anemia is often multifactorial, the specific entities can be grouped into three broad categories: (a) anemias due to causes more common in the elderly; (b) anemias without special predilection for the elderly; (c) anemias of unknown cause. The major biological questions concern the third category, which accounts for 14-17% of the anemias, and whether senescence itself contributes to anemia. Current opinion favors a diminished erythropoietic reserve with aging, but the data are inconsistent and the mechanism has not been established. It may be that cytokine modulation of erythropoiesis is abnormal. Some findings in unexplained anemia bear partial resemblance to the changes of anemia of chronic disease, suggesting the possibility that subtle unidentified inflammatory responses of unknown origin may be operative in many elderly people. Of the anemias of known cause that are especially common in the elderly, anemia of chronic disease is an important entity but is sometimes obscured or overlooked and its diagnosis rests on crude tests. Cobalamin deficiency is very common also, although most cases are mild and not accompanied by anemia. Because the basic diagnostic approach to anemia is neither complex nor very invasive and anemia may be a marker of poor prognosis, attribution of anemia to senescence is not advisable until other causes have been ruled out.

Deficiency of the specific granule proteins, R-binder/transcobalamin I and lactoferrin, in plasma and saliva: a new disorder.

The mechanisms of hereditary deficiency of R binder, which originates in neutrophils and exocrine gland epithelium, are unknown and may be multiple. This led us to examine if defective R binder synthesis also involves proteins that colocalize with it in neutrophil-specific granules and exocrine epithelial cells and may be under common regulatory control. Stored plasma and saliva samples from five unrelated R binder-deficient patients and control subjects were assayed for R binder, lactoferrin, cationic antimicrobial protein-18, neutrophil gelatinase-associated lipocalin, gelatinase, lysozyme, and myeloperoxidase. One patient, patient A, had lactoferrin levels below the limits of detection in both plasma and saliva in addition to his R binder deficiency. Although his deficiency involved lactoferrin as well, he had no history of predisposition to infection. PCR amplification of his R binder gene promoter region and the beginning of the first exon revealed no DNA abnormalities. His son and the son of his equally deficient brother, both presumptive heterozygotes, had mild deficiency of both R binder and lactoferrin. The results show that R binder deficiency exists in at least two forms. One, presumably the less common of the two forms, is the new hereditary entity described here, which is characterized by deficiency of more than one specific granule protein in both plasma and saliva. Despite this more widely distributed absence of the proteins than is found in congenital specific granule deficiency, infection posed no clinical problem in the affected patient.

Associations of food-cobalamin malabsorption with ethnic origin, age, Helicobacter pylori infection, and serum markers of gastritis.

OBJECTIVES: Food-cobalamin malabsorption is common in patients with low cobalamin levels. However, characterization of affected subjects has been limited. The aim of this study was to analyze demographic and gastric data in a large study population. METHODS: Data were collected prospectively in 202 subjects (43 volunteers and 159 patients) who underwent the egg yolk-cobalamin absorption test (EYCAT). H. pylori status was determined in 167 of the subjects, serum gastrin and antiparietal cell antibody in 158 and pepsinogen (PG) I and PG II levels in 133. RESULTS: Latin American and black patients had lower EYCAT results than did white or Asian-American ones (p = 0.0001) and had severe food-cobalamin malabsorption (EYCAT < 1%) more often (p = 0.0001). Age correlated inversely with EYCAT results (p = 0.02). H. pylori infection was associated with food-cobalamin malabsorption (p = 0.0001), especially with severe malabsorption where 29/37 subjects (78.4%) were infected. Malabsorption was also associated with higher gastrin levels (p = 0.0001) and lower PG I levels (p = 0.01) and PG I:PG II ratios (p = 0.0001). Multivariate analysis showed that ethnic origin, gastrin levels, H. pylori infection and, to a lesser extent, age were independently associated with the EYCAT results. CONCLUSIONS: Latin American and black patients have food-cobalamin malabsorption more often than do white and Asian-American patients. This association is independent of the malabsorption's association with H. pylori infection, markers of gastritis, such as gastrin, and older age. The patterns of gastric tests suggest that malabsorption may be due to diverse mechanisms, not just atrophic gastritis. The possible role of H. pylori infection in many cases of severe food-cobalamin malabsorption also suggests avenues of treatment and prevention.

High serum cobalamin levels in the clinical setting--clinical associations and holo-transcobalamin changes.

Whereas low cobalamin levels have been studied intensively, systematic information about high levels, especially in the clinical setting, is scarce. Therefore, a prospective comparison was done of 60 patients with high cobalamin levels and 75 with normal levels obtained by a hospital laboratory over a 2.5 month period. Associations with clinical disorders and laboratory test results were examined. Transcobalamin (TC) I and II were measured, especially the holoproteins (TC carrying circulating endogenous cobalamin) which were fractionated with microfine silica powder. High cobalamin levels (> 664 pmol/l; > 900 ng/l) occurred in 94 of 670 consecutive clinically requested assays (14%). The only independently significant associations with a high cobalamin level were renal failure among the clinical disorders (P=0.01), elevated serum creatinine (P=0.0001) and diminished albumin (P=0.0002) levels among laboratory tests. Both holo-TC I and holo-TC II levels were increased in renal failure (P=0.0001) but the increase was relatively greater in holo-TC II. The results indicate that high cobalamin levels are more frequent than low ones in clinical practice and appear to be associated often with renal failure. The elevation of both holo-TC II and holo-TC I suggests that several mechanisms are operative. The accumulation of holo-TC II suggests that cellular uptake of cobalamin by the abundant TC II receptors in the kidney may be impaired. The much better known association of high cobalamin levels with leucocytic disorders is rare, and no association was seen with liver disease.

Heterogeneity of gastric histology and function in food cobalamin malabsorption: absence of atrophic gastritis and achlorhydria in some patients with severe malabsorption.

BACKGROUND: The common but incompletely understood entity of malabsorption of food bound cobalamin is generally presumed to arise from gastritis and/or achlorhydria. AIM: To conduct a systematic comparative examination of gastric histology and function. SUBJECTS: Nineteen volunteers, either healthy or with low cobalamin levels, were prospectively studied without prior knowledge of their absorption or gastric status. METHODS: All subjects underwent prospective assessment of food cobalamin absorption by the egg yolk cobalamin absorption test, endoscopy, histological grading of biopsies from six gastric sites, measurement of gastric secretory function, assay for serum gastrin and antiparietal cell antibodies, and direct tests for Helicobacter pylori infection. RESULTS: The six subjects with severe malabsorption (group I) had worse histological scores overall and lower acid and pepsin secretion than the eight subjects with normal absorption (group III) or the five subjects with mild malabsorption (group II). However, histological findings, and acid and pepsin secretion overlapped considerably between individual subjects in group I and group III. Two distinct subgroups of three subjects each emerged within group I. One subgroup (IA) had severe gastric atrophy and achlorhydria. The other subgroup (IB) had little atrophy and only mild hypochlorhydria; the gastric findings were indistinguishable from those in many subjects with normal absorption. Absorption improved in the two subjects in subgroup IB and in one subject in group II who received antibiotics, along with evidence of clearing of H pylori. None of the subjects in group IA responded to antibiotics. CONCLUSIONS: Food cobalamin malabsorption arises in at least two different gastric settings, one of which involves neither gastric atrophy nor achlorhydria. Malabsorption can respond to antibiotics, but only in some patients. Food cobalamin malabsorption is not always synonymous with atrophic gastritis and achlorhydria, and hypochlorhydria does not always guarantee food cobalamin malabsorption.

Current concepts in cobalamin deficiency.

The application of sensitive metabolic tests, such as the deoxyuridine suppression test and measurement of homocysteine and methylmalonic acid, to cobalamin status has identified the entity of mild, preclinical cobalamin deficiency. This state, common in the elderly, responds to cobalamin therapy. Preclinical deficiency may exist within the nervous system as well, although this requires further study. Nevertheless, it is well to remember that not all low cobalamin levels and not all abnormal metabolite results reflect cobalamin deficiency. Interpretation of metabolic results still requires caution, as do proposals to raise the cut-off point for low cobalamin levels to capture some normal levels that are associated with metabolic abnormality. The recognition of mild, preclinical deficiency has opened up many important issues. These include identifying its causes, what should be done about it, and what the clinical impact of the hyperhomocysteinemia itself is. Although malabsorptive disorders, especially food-cobalamin malabsorption, underlie about half of all cases of preclinical deficiency, no cause can be found in the remainder of these cases; poor dietary intake appears to be uncommon. In addition, unusual states of neurologically symptomatic cobalamin deficiency are being recognized, such as nitrous oxide exposure in patients with unrecognized deficiency and severe deficiency in children of mildly deficient mothers. All of these have broadened and complicated the picture of cobalamin deficiency while providing greater opportunities for prevention.

Serum cobalamin, homocysteine, and methylmalonic acid concentrations in a multiethnic elderly population: ethnic and sex differences in cobalamin and metabolite abnormalities.

BACKGROUND: Low cobalamin concentrations and mild hyperhomocysteinemia are common in the elderly but ethnic differences have not been defined. OBJECTIVE: Our objective was to determine the demographic characteristics of cobalamin deficiency in the elderly and its role in their hyperhomocysteinemia. DESIGN: We measured serum cobalamin, total homocysteine (Hcys), and methylmalonic acid (MMA) concentrations in 725 subjects >60 y old, and folate concentrations in 520 subjects. RESULTS: After exclusion of subjects taking cobalamin supplements or with renal insufficiency, high prevalences of low cobalamin (11.8%), high MMA (16.6%), and high Hcys (26.1%) concentrations were seen. Most cobalamin concentrations <140 pmol/L appeared to reflect deficiency because 78. 3% of them were accompanied by abnormal metabolites. Subjects with cobalamin concentrations of 140-258 pmol/L had significantly fewer metabolic abnormalities. A low cobalamin concentration and renal insufficiency were the strongest predictors of abnormal Hcys concentrations. Elderly men had higher Hcys concentrations than did women (P = 0.0001). Whites and Latin Americans had lower cobalamin concentrations than did blacks and Asian Americans (P < 0.005). Whites also had higher Hcys concentrations than all the other groups (P < 0.05). When included in the analysis, renal insufficiency in subjects was associated with 23.8% of all high Hcys and 25.5% of all high MMA concentrations; most with renal insufficiency were Asian American and black men. CONCLUSIONS: Mild cobalamin deficiency is most common in elderly white men and least common in black and Asian American women. Hyperhomocysteinemia, which is most strongly associated with low cobalamin concentrations, is also most common in elderly whites, whereas that associated with renal insufficiency is more common in blacks and Asian Americans. Ethnic differences in cobalamin deficiency and the Hcys patterns associated with it or with renal insufficiency warrant consideration in supplementation strategies. Extending suspicion of deficiency to persons with cobalamin concentrations of 140-258 pmol/L appears to provide more disadvantages than advantages.

A focused approach to anemia.

If all the elements of the complete blood cell count are considered in clinical context, they can provide an invaluable guide to the possible causes of a patient's anemia and the tests needed for definitive diagnosis. Unnecessary tests not only add to the expense of treatment but may result in delayed diagnosis and inappropriate treatment in some cases.

Ethnic and racial factors in cobalamin metabolism and its disorders.

A growing body of data indicates the importance of ethnic and racial factors to many clinical and scientific considerations of cobalamin metabolism and its disorders. Blacks have significantly higher cobalamin and transcobalamin (especially transcobalamin II) levels than whites. Because serum cobalamin levels are often influenced by factors unrelated to cobalamin intake, stores, or deficiency, it is unclear whether the differences in levels reflect cobalamin status or not. The ethnic differences, which are present in cord blood, childhood, and pregnancy as well, probably arise from combinations of hereditary and acquired causes. It also appears that blacks have lower homocysteine levels than whites, metabolize homocysteine more efficiently, and do not show the same benefit from vitamin therapy. Modern surveys indicate that pernicious anemia is as common in blacks and, perhaps, Asian Indians as in whites. Moreover, the disease appears to be accelerated in blacks and, to a lesser extent, Latin Americans. Yet, for various reasons, such as the blunting or absence of hyperbilirubinemia and the frequent coexistence of microcytic disorders, cobalamin deficiency may be more difficult to recognize in blacks. Many of these observations of differences and new-found similarities raise important clinical and public health issues. Does the standard reference range for serum cobalamin, derived largely from white subjects, promote underrecognition of deficiency in blacks with their higher cobalamin levels? Or does it promote overdiagnosis of cobalamin deficiency in many whites with their lower levels? Given their lower rate of neural tube defects, possibly lower homocysteine levels, more efficient homocysteine metabolism and lesser impact of vitamin therapy on it, does the untargeted promotion of high folate intake provide less benefit to blacks than to whites while exposing them to an equal risk for adverse effects because of unrecognized pernicious anemia?

Dietary intake of cobalamin in elderly people who have abnormal serum cobalamin, methylmalonic acid and homocysteine levels.

OBJECTIVE: To determine if poor dietary intake can explain the cobalamin-related abnormalities often seen in the elderly. DESIGN: Prospective laboratory survey with a follow-up dietary assessment. SETTING: Social centers for the elderly and an outpatient clinic. SUBJECTS: Ninety-five free-living subjects >60y old with abnormal or suspicious findings in cobalamin-related tests and 78 subjects >60y old with normal results. INTERVENTIONS: Serum cobalamin, methylmalonic acid and homocysteine determinations to assess cobalamin status and a one year food-frequency questionnaire to assess cobalamin intake. RESULTS: Only three of the 173 subjects (1.7%), one of whom had normal cobalamin status, ingested <2 microg cobalamin/d, the Recommended Daily Allowance. Sixty-nine subjects (39.9%) ingested <6 microg/d, but they did not have more abnormal serum cobalamin or metabolite values than those ingesting >6 microg. Ordering all subjects by quintiles according to cobalamin intake revealed no significant trends or differences in any of the serum values either. Moreover, arranging subjects by results of tests of cobalamin status showed that the subjects with abnormal cobalamin status did not differ in cobalamin intake from those with normal cobalamin status, although they did differ in use of supplements. Finally, cobalamin intake, with or without supplements, did not correlate with serum cobalamin or metabolite levels. The absence of any association between cobalamin status and intake contrasts sharply with the significant correlation between folate intake and folate status (P = 0.0001). CONCLUSIONS: The high frequency of mildly abnormal cobalamin status in the elderly cannot be attributed to poor intake of cobalamin. Nondietary explanations, such as malabsorption and other phenomena, must always be sought to explain mild cobalamin deficiency in the elderly.

Cobalamin, the stomach, and aging.

Low cobalamin concentrations are common in the elderly. Although only a minority of such persons display clinically obvious symptoms or signs, metabolic data clearly show cellular deficiency of cobalamin in most cases. The evidence suggests that this is not a normal physiologic expression of the aging process. Rather, the elderly seem at increased risk for mild, preclinical cobalamin deficiency. Classical disorders such as pernicious anemia are the cause of this deficiency in only a small proportion of the elderly. A more frequent problem is food-cobalamin malabsorption, which usually arises from atrophic gastritis and hypochlorhydria but other mechanisms seem to be involved in some patients. The diminished absorption should not be viewed as a natural consequence of aging. The partial nature of this form of malabsorption produces a more slowly progressive depletion of cobalamin than does the more complete malabsorption engendered by disruption of intrinsic factor-mediated absorption. The slower progression of depletion probably explains why mild, preclinical deficiency is associated with food-cobalamin malabsorption more often than with pernicious anemia. Decisions about the optimal management of the very common problem of mild, preclinical cobalamin deficiency in the elderly await further clarification of the processes and the complex issues involved, including the possibility that routine nitrous oxide use during surgery, proposed dietary changes, and other practices may further stress the marginal cobalamin status of many elderly people.