B-vitamins and bone in health and disease: the current evidence.

Osteoporosis, a metabolic skeletal disease characterised by decreased bone mass and increased fracture risk, is a growing public health problem. Among the various risk factors for osteoporosis, calcium and vitamin D have well-established protective roles, but it is likely that other nutritional factors are also implicated. This review will explore the emerging evidence supporting a role for certain B-vitamins, homocysteine and the 677 C → T polymorphism in the gene encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase, in bone health and disease. The evidence, however, is not entirely consistent and as yet no clear mechanism has been defined to explain the potential link between B-vitamins and bone health. Coeliac disease, a common condition of malabsorption, induced by gluten ingestion in genetically susceptible individuals, is associated with an increased risk both of osteoporosis and inadequate B-vitamin status. Given the growing body of evidence linking low bone mineral density and/or increased fracture risk with low B-vitamin status and elevated homocysteine, optimal B-vitamin status may play an important protective role against osteoporosis in coeliac disease; to date, no trial has addressed this possible link.

Increasing numbers at a specialist coeliac clinic: contribution of serological testing in primary care.

BACKGROUND: Serological testing, using IgA class endomysial and tissue transglutaminase antibodies has high sensitivity and specificity for coeliac disease and allows case finding by clinicians other than gastroenterologists. We reviewed new coeliac patients seen over a 9-year period to determine how the availability of serology, particularly to primary care physicians, has changed rates and sources of diagnosis. METHODS: Files of patients attending a specialist coeliac clinic who were diagnosed from 1996 through 2004 were reviewed. Patients with villous atrophy consistent with gluten sensitive enteropathy (Marsh III) on duodenal biopsy were selected. Data analysed included clinical characteristics, endomysial and tissue transglutaminase antibodies status and source of request for serology. RESULTS: Over the study period 347 new coeliac patients, comprising adults and children aged 10 years and over, were identified, of whom 163 (47%) were identified by serological testing in primary care, 152 (44%) at the hospital gastroenterology department and 32 (9%) by other physicians in secondary care. Over three consecutive 3-year periods, the percentage of patients identified in primary care rose from 28% through 47% to 60%, with a rise in total numbers diagnosed from 93 through 118 to 136. There was no change in patient clinical characteristics over the study period. Though tissue transglutaminase antibodies were less sensitive than endomysial antibodies, combined testing obtained a sensitivity of over 90%. Patients identified in primary care were significantly younger and more likely to present with diarrhoea as a primary symptom. CONCLUSION: Currently over half of our coeliac patients are identified by serological testing in primary care, which has resulted in an overall rise in diagnosis rates. Primary care practitioners have an important role in the diagnosis of coeliac disease, particularly of patients who present with non-gastrointestinal symptoms. The contribution of specialists other than gastroenterologists in secondary care is disappointing and may improve with directed education.

Histology of the terminal ileum in coeliac disease.

BACKGROUND: The histological lesion of gluten sensitivity primarily affects the proximal small bowel. The purpose of this study was to assess whether there were features of gluten-sensitive enteropathy in biopsies taken from the terminal ileum during colonoscopy/ileoscopy. Specific and sensitive abnormalities might facilitate diagnosis of coeliac disease in patients undergoing colonoscopy as their initial procedure or help select those who should proceed to upper gastrointestinal endoscopy and duodenal biopsy. METHODS: Terminal ileal biopsies, taken from 30 patients with duodenal villous atrophy consistent with coeliac disease and from 60 control patients with no evidence of coeliac or inflammatory bowel disease, were reviewed blindly and compared. Biopsies were assessed for the presence or absence of villous atrophy and crypt hyperplasia, and counts were made of intraepithelial lymphocytes (IELs). RESULTS: One patient only, in the coeliac group, had partial villous atrophy with crypt hyperplasia in the terminal ileum. IEL counts were significantly higher (P< 0.005) in the coeliac group than among controls (mean per 100 enterocytes 26 versus 10). An ileal IEL count > or =25 had a sensitivity for duodenal villous atrophy (VA) of 60% and specificity of 100%. CONCLUSIONS: Coeliac disease may affect the entire small bowel. Increased IEL density in the terminal ileum is associated with duodenal VA and should prompt a search for coeliac disease by serology and duodenal biopsy. Conversely, a normal IEL count does not allow the exclusion of coeliac disease with confidence.

Colon neoplasia co-existing with coeliac disease in older patients: coincidental, probably; important, certainly.

BACKGROUND: Coeliac disease and colorectal neoplasia are both common, present most often in patients over 40 and cause similar symptoms. Greater awareness and early use of serological tests have improved the diagnosis of coeliac disease, but raise the concern that co-existing colorectal neoplasia may be missed. This study assessed the prevalence of colorectal neoplasia among patients with coeliac disease diagnosed after the age of 40 who presented with altered bowel habit or iron deficiency. METHODS: All patients meeting the above criteria underwent colonoscopy unless this or barium enema had been performed shortly before. RESULTS: Of 69 patients with coeliac disease undergoing colonoscopy, 7 (10%) had colon neoplasia: 5 had tubulovillous polyps, and 2 had carcinoma. The prevalence figures for coeliac patients undergoing colonoscopy with iron deficiency and altered bowel habit alone were 11% (5 of 47) and 10% (2 of 22), respectively None of a further 13 who had undergone previous colon investigation (all by barium enema) had neoplasia, although these were probably a selected population. The seven patients with colorectal neoplasia had not reported rectal bleeding. The prevalence of colorectal neoplasia was not significantly higher than in two series of non-coeliac patients undergoing colonoscopy for investigation of iron deficiency (12%) or altered bowel habit (8%). CONCLUSIONS: There is a high prevalence of colorectal neoplasia among older patients with coeliac disease who present with iron deficiency or altered bowel habit, though this is no higher than for non-coeliac patients with these presentations. The possibility of dual pathology should be considered and excluded by colon investigation.

Transthyretin values correlate with mucosal recovery in patients with coeliac disease taking a gluten free diet.

AIMS: To assess changes in indicators of nutrition and iron deficiency as possible non-invasive markers of mucosal recovery in patients with coeliac disease on a gluten free diet. METHODS: Concentrations of transthyretin, retinol binding protein, soluble transferrin receptor, IgA anti-gliadin, and IgA anti-transglutaminase, and titres of IgA anti-endomysial antibody were measured in 36 newly diagnosed adult patients with coeliac disease and duodenal villous atrophy before (T0) and after one year (T1) on a gluten free diet. Duodenal biopsies taken at T0 and T1 were compared and graded as no improvement (no change in initial grade of villous atrophy) or improvement. RESULTS: Twenty two patients showed histological improvement and 14 showed no improvement. Transthyretin values increased in all patients with mucosal improvement and decreased in all patients showing no improvement. However, transthyretin values did not correlate with the degree of villous atrophy at T0 and T1 when assessed separately. Changes in retinol binding protein and soluble transferrin receptor values did not correlate with mucosal improvement. Coeliac disease associated antibodies (to gliadin, endomysium, and transglutaminase) decreased in most patients between T0 and T1, irrespective of mucosal recovery. CONCLUSIONS: Serial but not single measurements of transthyretin may be used as a non-invasive test to monitor mucosal recovery and therefore reduce the need for, or frequency of, follow up biopsies in treated patients with coeliac disease.

Disappointing sensitivity of endoscopic markers for villous atrophy in a high-risk population: implications for celiac disease diagnosis during routine endoscopy.

OBJECTIVE: Endoscopic markers of duodenal villous atrophy (VA) can facilitate diagnosis of celiac disease during routine upper GI endoscopy. We studied their sensitivity for VA in a large series of patients undergoing GI endoscopy specifically for duodenal biopsy. Poor sensitivity in this setting would have significant and adverse implications for their performance during routine endoscopy. METHODS: All patients with VA on duodenal biopsy performed for positive serum endomysial antibody (EmA) and/or clinical features suggestive of celiac disease were included. The second part of duodenum was inspected carefully for endoscopic markers using videogastroscopes. RESULTS: Of 129 patients studied, 99 (77%) had at least one endoscopic markers. The most commonly seen marker were a mosaic pattern mucosa (68 patients, 53%) and scalloping of duodenal folds (74 patients, 57%). The prevalence of markers was significantly lower for partial VA (15 of 26 patients, 58%) than for subtotal or total VA (84 of 103 patients, 82%) (p < 0.02). CONCLUSIONS: Endoscopic markers have disappointing sensitivity even in a population at high risk of celiac disease, particularly for partial VA. Their performance may be even poorer in an unselected dyspeptic population. Although they may help improve diagnosis rates among patients with nonspecific dyspeptic symptoms, many patients, particularly those with milder enteropathy, will be missed. As celiac disease is an important cause of dyspepsia, consideration should be given to serological screening to further improve diagnosis rates, as few centers will have the resources to routinely biopsy all patients.

Sensitivity of serum tissue transglutaminase antibodies for endomysial antibody positive and negative coeliac disease.

BACKGROUND: Serum antibodies to tissue transglutaminase (tTGA) are reported to have high sensitivity and specificity for coeliac disease and to correlate closely with endomysial antibodies (EmA). We assessed their performance in a coeliac population with a high proportion of EmA-negative patients, who have been under-represented in previous studies. METHODS: We used a commercial ELISA kit to test for IgA class tTGA in sera from a population of 73 untreated coeliac patients with normal serum IgA and a high percentage (19%) EmA-negative, taking 58 patients with normal duodenal biopsies as controls. EmA was measured using indirect immunofluorescence. RESULTS: Forty-six (63%) patients with villous atrophy (VA) had both tTGA and EmA. However, when considered separately, sensitivities of tTGA and EmA for VA were similar (75% versus 81%) and both had high specificity (98% versus 97%). As 9 patients were tTGA-positive only and 13 had EmA only, selection of patients for biopsy on the presence of either antibody would have had a sensitivity of 93% (68 of 73), with 5 (7%) patients seronegative for both. CONCLUSION: Although the ELISA tTGA assay is more convenient than EmA testing, it offers no advantages in sensitivity or specificity if used in isolation. However, incomplete concordance between EmA and tTGA positivity means that combination screening with both assays offers higher sensitivity, as almost a third of patients have only one antibody. As some coeliac patients with normal serum IgA are negative for both antibodies, biopsies should still be performed in seronegative individuals deemed at high risk for coeliac disease.

Proliferative activity in craniopharyngiomas: clinicopathological correlations in adults and children.

BACKGROUND: Craniopharyngiomas are slow-growing, locally invasive intracranial tumors that can generate considerable morbidity, and recurrences are often difficult to manage. Because reliable morphologic criteria for accurately predicting the clinical outcome of these tumors are lacking, we evaluated the growth potential of craniopharyngiomas by measuring their proliferative activity based on MIB-1 immunostaining for the Ki-67 antigen, which is expressed during all phases of the cell cycle except G(0.) METHODS: Paraffin sections from 37 cases of craniopharyngiomas were immunostained with the monoclonal antibody MIB-1, and a labeling index was derived in each case from an the with the highest labeling. RESULTS: MIB-1 immunoreactivity was mainly confined to the peripheral palisaded epithelium of craniopharyngiomas. In adult craniopharyngiomas, MIB-1 labeling indices (MIB-LI) varied from 0.1% to 34.6% (mean 8.9%; SD 9. 8), and in pediatric tumors the indices ranged from 1.8% to 15.0% (mean 6.3%; SD 3.7). MIB-LI was not found to be an independent predictor of recurrence, although in all the pediatric cases that recurred, MIB-LI in the second specimen was greater. CONCLUSIONS: The actively proliferating compartment in craniopharyngiomas seems to be the peripheral palisaded epithelium. Low MIB-LI observed in the majority of tumors is in concordance with the slow growth and low-grade invasiveness associated with craniopharyngiomas. However, unlike other intracranial neoplasms, where Ki-67 labeling indices have been useful in predicting tumor behavior, a clear relationship could not be demonstrated between MIB-1 immunoreactivity, morphological features and clinical outcomes in adults or children with craniopharyngiomas.

Hemorrhoid banding using videoendoscopic anoscopy and a single-handed ligator: an effective, inexpensive alternative to endoscopic band ligation.

OBJECTIVE: We evaluated a technique of hemorrhoid banding using videoscopic anoscopy and a single-handed ligator that offers substantial cost savings over endoscope-mounted devices. METHODS: Patients with rectal bleeding from grade II/III hemorrhoids had videoscopic anoscopy, which provided a magnified view, allowing accurate localization of the hemorrhoids and the dentate line before banding, and a photographic record, if required. Banding was performed using a suction ligator that could be operated by one hand, allowing the other to control the anoscope. RESULTS: Of 39 patients with second- and third-degree hemorrhoids, 34 (87%) had no further bleeding after a single banding session and a further three had no recurrence after a second session. The only complications were pain (one patient) and infection (one patient). CONCLUSIONS: This method is convenient and effective, costing per procedure less than one-tenth of endoscope-mounted band ligators. We recommend its use in preference if magnified views and a photographic record are required. However, its cost and complexity, compared with traditional hemorrhoid banding, may mean that the latter is preferred in the office setting.

Disappearance of endomysial antibodies in treated celiac disease does not indicate histological recovery.

OBJECTIVE: Although serum IgA-class endomysial antibody (EmA) has high sensitivity for villous atrophy (VA) in patients with untreated celiac disease, few studies have attempted to correlate EmA seroconversion with histological recovery after starting a gluten-free diet. We prospectively studied changes in EmA status and in duodenal histology of seropositive patients after dietary treatment. METHODS: Patients with VA and EmA had repeat EmA testing at 3, 6, and 12 months after starting gluten-free diet, plus assessment of dietary compliance by dietitians and follow-up duodenal biopsy at 12 months. VA before and after treatment was classified as partial (P), subtotal (ST), and total (T). RESULTS: Of 77 patients with newly diagnosed VA and without IgA deficiency, 62 (81%) had EmA: 46 of 57 (81%) with T or STVA and 16 of 20 (80%) with PVA. Of 53 initially EmA-positive patients who completed study criteria, EmA was undetectable in 31 patients (58%) after 3 months' diet, in 40 (75%) after 6 months, and in 46 (87%) after 12 months. However, only 21 patients (40%), all seronegative by 12 months, had complete villous recovery. Only three (33%) of 10 patients with persisting ST or TVA and two (9%) of 22 with PVA remained EmA positive. Four of the five patients with persisting EmA had poor dietary compliance. CONCLUSIONS: EmA is a poor predictor of persisting VA after patients have started gluten-free diet, although it may be of value in monitoring dietary compliance. Although there are no clear guidelines regarding the need for follow-up biopsy, EmA seroconversion cannot substitute. The apparent association between dietary compliance and seroconversion suggests that gluten intake may determine whether untreated celiac patients are EmA positive or negative for a given degree of small bowel damage.

Reliance on serum endomysial antibody testing underestimates the true prevalence of coeliac disease by one fifth.

BACKGROUND: Although IgA endomysial antibody (EmA) is currently the serologic test of choice in selecting suspected coeliac patients for duodenal biopsies, false-negative cases have been reported and may be more common than previous studies suggest. We assessed the sensitivity of EmA for patients with biopsy-confirmed villous atrophy (VA). METHODS: We studied 89 patients without IgA deficiency for whom biopsy had not been primarily prompted by a positive EmA result. VA was graded as partial, subtotal, or total (PVA, STVA, TVA). Serum EmA was assayed with indirect immunofluorescence. RESULTS: The sensitivity of EmA for VA was 78% (69 of 89) and was similar for PVA (79%) and ST/TVA (77%). Only 4 of the 20 EmA-negative patients had increased serum IgA-class antigliadin antibody levels as measured with enzyme-linked immunosorbent assay. All seronegative patients who complied with dietary gluten exclusion responded clinically, with histologic improvement after 12 months in 8 (67%) of 12 patients who had follow-up biopsies. CONCLUSIONS: EmA-negative coeliac disease is common. Reliance on EmA testing to select patients for biopsy will result in significant underdiagnosis.

Prevalence of celiac disease and its endoscopic markers among patients having routine upper gastrointestinal endoscopy.

OBJECTIVE: The aim of this study was to determine the prevalence of duodenal villous atrophy (VA) among patients undergoing routine upper gastrointestinal (GI) endoscopy and the value of endoscopic markers for VA in selecting patients for duodenal biopsy. METHODS: One hundred and fifty adult patients with upper GI symptoms or iron-deficiency anemia had inspection and biopsy of the second part of the duodenum during endoscopy. Endoscopic markers for VA sought were mosaic or nodular mucosa, scalloping of duodenal folds, and reduction in number or absence of duodenal folds. RESULTS: Endoscopic markers were seen in seven patients (5%): scalloped folds with mosaic pattern mucosa (three patients), scalloped folds, reduced in number with mosaic pattern mucosa (three patients), and nodular mucosa with reduction in fold numbers (one patient). All seven patients had partial, subtotal, or total VA. One of 143 patients with no endoscopic abnormality had patchy VA. The prevalence of VA was thus 1:19 (8 of 150). Endoscopic markers had a sensitivity of 87.5% (7 of 8), specificity of 100% (142 of 142), positive predictive value of 100% (7 of 7), and negative predictive value of 99% (142 of 143). Of the eight patients with VA, the indications for endoscopy were upper GI symptoms in seven patients (two with anemia) and anemia without GI symptoms in one. After 6 months of dietary gluten exclusion, improvement by at least one criterion was documented in all eight patients. CONCLUSIONS: Careful inspection of the duodenum during routine upper GI endoscopy allows accurate selection of patients for biopsy but may not detect patchy VA or milder enteropathy. Celiac disease should be considered as a cause of dyspeptic and reflux symptoms, as well as of iron-deficiency anemia.

Quantification of lymph nodes in selective neck dissection.

OBJECTIVES: Provide reference for surgeon and pathologist regarding expected yield from selective neck dissections. Quantify lymph nodes obtained from cadaver dissection based on current nodal classification and compare with clinical series. STUDY DESIGN: 1. Quantification of lymph nodes at levels I-V harvested from human cadavers and correlation with nodal grouping for supraomohyoid (I-III) and lateral (II-IV) neck dissections. 2. Retrospective review of operative specimens from clinical neck dissections for lymph node quantity. METHODS: 1. Twenty radical neck dissection specimens, harvested from 10 fresh human cadavers without evidence of head and neck cancer, were separated by nodal level for gross and microscopic examination by a pathologist. The quantity of nodes obtained per level for each specimen was tabulated. 2. Charts of patients treated with neck dissection for squamous cell carcinoma were reviewed and tabulated for type of dissection and number of lymph nodes reported. RESULTS: In the 20 cadaver neck dissections, the average number of lymph nodes removed for levels I-V was 24, with 13 for levels I-III and 19 for levels II-IV. In the clinical review, 98 total neck dissections were included. In the six supraomohyoid dissections, an average of 20 lymph nodes (range, 14-26) were found, with an average of 30 (range, 15-43) in the 11 lateral compartment specimens. In 81 radical or modified radical dissections, an average of 31 nodes (range, 19-63) was reported. CONCLUSIONS: The number of lymph nodes removed in selective neck dissection should be comparable to that of the corresponding levels in radical neck dissection, provided that strict adherence to surgical boundaries is maintained. Dissection of normal cadavers provides a reference for the surgeon and the pathologist but may under-represent lymph node quantity in the diseased state.

Combined effects of HIV-infection status and psychosocial vulnerability on mental health in homosexual men.

The present study examines psychiatric symptomatology and syndromal depression among 174 HIV+ and 760 HIV- homosexual men enrolled in the Pittsburgh site of the Multicenter AIDS Cohort Study (MACS). A central study goal was to determine whether men's psychosocial status in the areas of demographics, social supports, and coping, in combination with their HIV-infection status, was associated with mental health. Cross-sectional analyses indicated that HIV+ men had significantly higher levels of psychiatric symptomatology and syndromal depression than HIV- men. However, multivariate analyses showed that these associations only appeared among HIV+ men with certain psychosocial characteristics. HIV+ men who were younger, lacked full-time employment, claimed relatively high support from their relatives, and demonstrated high use of active behavioral coping strategies were at greater risk for psychiatric symptomatology and/or syndromal depression. Further, sense of mastery and frequent use of avoidant coping strategies were highly predictive of psychiatric outcomes irrespective of HIV status. The findings suggest that knowledge of an individual's HIV status per se will be inadequate for valid assessment of psychological risks. Rather, any association of HIV status and mental health will depend largely on other psychosocial characteristics that foster vulnerability or resistance to distress in these men.

Celiac disease presenting as the Paterson-Brown Kelly (Plummer-Vinson) syndrome.

We describe two patients with Paterson-Brown Kelly (Plummer-Vinson) syndrome whose iron deficiency anemia was due to celiac disease. They presented with dysphagia 13 and 9 yr, respectively, before celiac disease was diagnosed. Neither had gastrointestinal symptoms suggestive of malabsorption. Celiac disease is a recognized cause of chronic iron deficiency and should be considered as an etiological factor for sideropenic dysphagia.