A case series to describe the clinical characteristics of foot ulceration in patients with rheumatoid arthritis

The aim of this study was to describe the clinical characteristics of foot ulceration in patients with rheumatoid arthritis (RA). Adults with RA and current foot ulceration but without diabetes were recruited. Clinical examination included assessment of RA disease activity, foot deformity, peripheral vascular disease, neuropathy and plantar pressures. Location, wound characteristics and time to healing were recorded for each ulcer. Participants completed the Health Assessment Questionnaire and Leeds Foot Impact Scale. Thirty-two cases with 52 current ulcers were recruited. Thirteen patients (41%) experienced more than one current ulcer: 5 (16%) had bilateral ulceration, 15 (47%) had previous ulceration at a current ulcer site. The majority (n = 33) of open ulcers were located over the dorsal aspect of the interphalangeal joints (n = 12), plantar aspect of the metatarsophalangeal joints (MTPJs) (n = 12) and medial aspect of first MTPJs (n = 9). In ulcerated limbs (n = 37), ankle brachial pressure index (ABPI) was <0.8 in 2 (5%); protective sensation was reduced in 25 (68%) and peak plantar pressures were >6 kg/cm² in 6 (16%). Mean ulcer size was 4.84 by 3.29 mm. Most ulcers (n = 42, 81%) were superficial; five (9.6%) were infected. Time to healing was available for 41 ulcers: mean duration was 28 weeks. Three ulcers remained open. In conclusion, foot ulceration in RA is recurrent and multiple ulcers are common. Whilst ulcers are small and shallow, time to achieve healing is slow, posing infection risk. Reduced protective sensation is common in affected patients. The prevalence of arterial disease is low but may be under estimated due to high intolerance of ABPI.     

HLA class 1 associations in Henoch Schonlein purpura: increased and decreased frequencies

Henoch Schonlein purpura (HSP) is the most common vasculitis of childhood. Susceptibility to HSP and associated clinical heterogeneity in HSP may be conferred by a number of genetic loci, including the major histocompatibility complex. We aimed to investigate the implications of the human leukocyte antigen (HLA) class 1 alleles in susceptibility to HSP and determine the possible associations with renal, gastrointestinal (GI), and joint manifestations of the disease. 110 children with HSP (66 boys, 44 girls) and 250 unrelated healthy controls were enrolled in the study. The mean age was 8.65 ± 3.59 years. HSP was diagnosed on the basis of clinical and laboratory data according to the American College of Rheumatology classification. The diagnosis was supported with skin and/or kidney in most of the patients. Clinical and laboratory findings revealed: skin involvement in 110 (100%), joint manifestations in 82 (74.5%), GI symptoms in 58 (52.7%), and hematuria and/or proteinuria in 36 (32.7%) patients. HLA class 1 alleles were identified by DNA amplification, hybridized with specific primer sequences. Comparison of frequencies between patients and controls were made by using the Fisher’s exact test. Odds ratio (OR) was used as the measure of association. HLA A2, A11, and B35 antigens showed an increased risk for predisposition to HSP (OR = 1.714, 95%CI = 1.088–2.700, p = 0.020; OR = 2.185, 95%CI = 1.289–3.703, p = 0.003; and OR = 2.292, 95%CI = 1.451–3.619, p = 0.000, respectively), while HLA A1, B49, and B50 antigens revealed decreased risk for predisposition to HSP (OR = 4.739, 95%CI = 1.828–12.345, p = 0.001; OR = 3.268, 95%CI = 0.955–11.236, p = 0.047; and OR = 7.462, 95%CI = 0.975–55.555, p = 0.024, respectively). Considering the renal involvement and severity of proteinuria, there was no association with HLA class 1 alleles. Our results suggest that the increased frequency of HLA A2, A11, and B35 alleles in unselected pediatric HSP patient population and miscarrying of HLA A1, B49, and B50 could be considered as a risk factor for susceptibility to HSP.     

Lipoprotein receptor associated protein (LRPAP1) insertion/deletion polymorphism: association with gallbladder cancer susceptibility

Background Low-density lipoprotein receptor-related protein associated protein (LRPAP1) insertion/deletion polymorphism influences cholesterol homeostasis and may confer risk for gallstone disease and gallbladder carcinoma (GBC) incidence usually parallels with the prevalence of cholelithiosis. Aim We aimed to examine the role of LRPAP1 polymorphism in susceptibility to GBC. Methods Present case control study included 129 proven GBC patients, 183 gallstone patients, and 208 healthy controls. Genotyping was done by polymerase chain reaction–restriction fragment length polymorphism method. Results The D allele of LRPAP1 was significantly higher in GBC patients as compared to gallstone patients (p = 0.013; OR = 1.6, 95% CI = 1.1–2.4). However, II genotype and I allele was associated with reduced risk of GBC as compared to gallstone patients (p = 0.002; OR = 0.1, 95% CI = 0.1–0.6; p = 0.013; OR = 0.6, 95% CI = 0.4–0.8) The increased risk due to D allele was limited to female GBC patients (p = 0.021; OR = 1.8, 95% CI = 1.1–3.0). However, reduced risk due to II genotype and I allele was observed which was also confined to female GBC patients (p = 0.005; OR = 0.1, 95% CI = 0.1–0.6; p = 0.021; OR = 0.5, 95% CI = 0.3–0.8). On comparing GBC patients having gallstone with gallstone patients, high risk was observed in the GBC patients having gallstone due to the presence of D allele (p = 0.032; OR = 1.7, 95% CI = 1.0–2.8). However, low risk was observed because of I allele in GBC patients with gallstone in comparison to gallstone patients (p = 0.032, OR = 0.6, 95% CI = 0.4–0.9). Conclusion It appears that ‘D’ allele may modulate the susceptibility of GBC, and the risk is independent to genetic risk of gallstone.     

The effect of smoking after surgery for Crohn’s disease: a meta-analysis of observational studies

Objective  The aim of the study was to quantify the risk of disease recurrence associated with cigarette smoking for individuals with Crohn’s disease after disease-modifying surgery. Design  Meta-analysis of observational studies. Data sources  Medline, Embase, Ovid and the Cochrane database. Materials and methods  A literature search was performed to identify studies published between 1966 and 2007 comparing outcomes of smokers, ex-smokers and non-smokers with Crohn’s disease. Random-effect meta-analytical techniques were employed to assess the risk of medical or surgical recurrence. Results  Sixteen studies encompassing 2,962 patients including 1,425 non-smokers (48.1%), 1,393 smokers (47.0%) and 137 ex-smokers (4.6%) were included. Smokers had significantly higher clinical post-operative recurrence than non-smokers (odds ratio [OR] = 2.15; 95%CI = 1.42, 3.27; p < 0.001). Smokers were also more likely to experience surgical recurrence by 5 (OR = 1.06; 95%CI = 0.32; 3.53, p = 0.04) and 10 years of follow-up (OR = 2.56; 95%CI = 1.79, 3.67; p < 0.001) compared to non-smokers, although the crude re-operation rate was not statistically significant. When matched for operation and disease site, smokers had significantly higher re-operation rates to non-smokers (OR = 2.3; 95%CI = 1.29, 4.08; p = 0.005). There was no significant difference between ex-smokers and non-smokers in re-operation rate at 10 years (OR = 0.30; 95%CI = 0.09, 1.07; p = 0.10) or in post-operative acute relapses (OR = 1.54; 95%CI = 0.78, 3.02; p = 0.21). Conclusions  Patients with Crohn’s disease who smoke have a 2.5-fold increased risk of surgical recurrence and a twofold risk of clinical recurrence compared to non-smokers. Patients with Crohn’s disease should be encouraged to stop smoking since the risk of disease relapse is minimised upon its cessation. George E. Reese and Theodore Nanidis with equal contribution.     

The predictors of foot ulceration in patients with rheumatoid arthritis

This study was conducted to determine the predictors of foot ulceration occurring in patients with rheumatoid arthritis (RA) without diabetes. A multi-centre case control study was undertaken; participants were recruited from eight sites (UK). Cases were adults diagnosed with RA (without diabetes) and the presence of a validated foot ulcer, defined as a full thickness skin defect occurring in isolation on / below the midline of the malleoli and requiring > 14 days to heal. Controls met the same criteria but were ulcer naive. Clinical examination included loss of sensation (10g monofilament); ankle-brachial pressure index (ABPI); forefoot deformity (Platto); plantar pressures (PressureStat); RA disease activity (36 swollen/tender joint counts) and the presence of vasculitis. History taking included past ulceration/foot surgery; current medication and smoking status. Participants completed the Health Assessment Questionnaire (HAQ) and Foot Impact Scale. A total of 83 cases with 112 current ulcers and 190 ulcer naïve controls participated. Cases were significantly older (mean age 71 years; 95 % confidence interval [CI], 69–73 vs. 62 years, 60–64) and had longer RA disease duration (mean 22 years; 19–25 vs. 15, 13–17). Univariate analysis showed that risk of ulceration increases with loss of sensation; abnormality of ABPI and foot deformity. Plantar pressures and joint counts were not significant predictors. HAQ score and history of foot surgery were strongly associated with ulceration (odds ratio [OR]?=?1.704, 95 % CI 1.274–2.280 and OR?=?2.256, 95 % CI 1.294–3.932). Three cases and two controls presented with suspected cutaneous vasculitis. In logistic regression modelling, ABPI (OR?=?0.04; 95 % CI, 0.01–0.28) forefoot deformity (OR?=?1.14; 95 % CI, 1.08–1.21) and loss of sensation (OR?=?1.22; 95 % CI, 1.10–1.36) predicted risk of ulceration. In patients with RA, ABPI, forefoot deformity and loss of sensation predict risk of ulceration but, in contrast with diabetes, raised plantar pressures do not predict risk.     

Study of 18 functional hemostatic polymorphisms in mucocutaneous bleeding disorders

Hereditary disorders of primary hemostasis, characterized by mucocutaneous bleeding (MCB), are highly prevalent in children. Few cases are clearly monogenic, but the overwhelming majority are classified as mild bleeding disorders, with wide clinical and laboratory heterogeneity suggestive of complex polygenic diseases. In this framework, and by homology with venous thrombosis, some functional polymorphisms affecting the hemostatic system should be considered. We evaluated the role of 18 common hemostatic polymorphisms on the occurrence and severity of MCB in a case–control study including 269 patients and 286 matched controls consecutively recruited. FV Leiden was associated with milder bleeding severity, assessed by a standardized bleeding score (p = 0.013). Multivariate analysis revealed that three additional polymorphisms protected against MCB (F13 Leu34, OR = 0.66; 95% CI, 0.47–0.94; p = 0.024; VKORC1 1173T, OR = 0.59; 95% CI, 0.40–0.87; p = 0.009; and non-O blood group alleles, OR = 0.59; 95% CI, 0.41–0.86; p = 0.006). When combined, these polymorphisms showed an additive protection (OR = 0.24; 95% CI, 0.11–0.52), supporting the polygenic nature of MCB. Our data suggest that some common polymorphisms affecting hemostasis-related genes could protect from bleeding.     

Cytotoxic T lymphocyte antigen-4 promoter ?658CT gene polymorphism is associated with ulcerative colitis in Chinese patients

Background and aim  Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a role in the downregulation of T cell activation. The present study aimed to examine an association between the CTLA-4 gene polymorphisms and ulcerative colitis (UC) in the Han Chinese in central China. Materials and methods  One hundred seventeen patients with UC and 246 healthy controls were genotyped for CTLA-4 gene −658CT in the promoter and CT61 at the 3′ untranslated region using a method of polymerase chain reaction-based restriction fragment length polymorphism and single-strand conformation polymorphism, respectively. The distributions of the genotypes and the allele frequencies of the CTLA-4 gene in UC patients and healthy controls were compared by chi-square test. Results  The frequency of the T/T+C/T genotype at the CTLA-4 gene −658CT in the promoter was significantly higher in UC patients than in healthy controls (26.5% vs 15.4%, χ ² = 6.287, P = 0.015, OR = 1.973, 95%CI = 1.153–3.375). The frequency of the T allele at the CTLA-4 −658CT was also significantly higher in UC patients than in the controls (13.2% vs 8.1%, χ ² = 4.707, P = 0.033, OR = 1.726, 95%CI = 1.049–2.838). The frequency of the T/T genotype at the −658 locus was highly associated with extensive colitis in UC patients (P = 0.037, OR = 3.955, 95%CI = 1.068–14.647). The frequency of the T allele at the −658 locus was highly associated with extensive colitis in UC patients (P = 0.0067, OR = 3.05, 95%CI = 1.320–7.048). Conclusion  The T allele of CTLA-4 −658 polymorphism in the promoter of CTLA-4 gene was highly associated with UC in the Han Chinese in central China.     

Caregiver Time and Cost of Home Care for Alzheimer’s Disease: A Clinic-based Observational Study in Beijing,China

This cross-sectional study was conducted to estimate the caregiver time and calculate the cost of informal care for AD, and to explore the potential predictors of caregiver time. Seventy-one community-dwelling AD patient-caregiver dyads completed the assessment and questionnaire. AD patients were assessed with Mini-mental status examination (MMSE), activities of daily living (ADL), and Neuropsychiatric Inventory (NPI). Caregiver time was recorded using the Resource Utilization in Dementia (RUD). According to the MMSE score, subjects were classified as mild (n = 18), moderate (n = 43), and severe (n = 10) groups. The PADL care time was significantly different among three groups, with highest in severe group (172.5 ± 208.0 h/month), and least in mild group (24.9 ± 70.5 h/month) (F = 5.215, df = 2, P = 0.008). The supervision time was higher in severe group compared to mild group (F = 3.330, df = 2, P = 0.042), while there were no differences between mild and moderate groups, and between moderate and severe groups. There was no difference in IADL caregiver time among three groups. The estimated annual cost of PADL care ranged from 903 USD (mild) to 6,259 USD (severe), IADL care from 4042USD to 7645USD, and supervision from 871 USD to 6,172 USD. Stepwise logistic regression analysis showed that MMSE score was significant predictor of PADL care time. For every one unit increase in MMSE, the odds of PADL care time decrease by a factor of 0.791 (χ2 = 13.628, P = 0.000). Spouse caregivers significantly predict greater IADL care time (OR = 4.469, 95%CI = 1.248–15.999, P = 0.021), and male caregiver was a protector for IADL care time (OR = 0.157, 95%CI = 0.040–0.609, P = 0.007). The ADL score was a significant predictor of supervision time. For every one unit increase in ADL, the odds of supervision time increase by a factor of 1.132 (95%CI = 1.055–1.215, P = 0.001). Higher educational level of the patient predicted decrease in supervision time (OR = 0.888, 95%CI = 0.794–0.994, P = 0.038). Caregiver time and cost of home care for AD was substantial in China. Care time of PADL increased with the progression of cognitive decline. The IADL care time was strongly influenced by the biographical characteristics of caregivers. Supervision was mostly predicted by the functional status of the patient.     

Incidence,consequences, and risk factors for anastomotic dehiscence after colorectal surgery: a prospective monocentric study

Background Anastomotic dehiscence is the most severe surgical complication after large bowel resection. This study was designed to assess the incidence, to observe the consequences, and to identify the risk factors associated with anastomotic leakage after colorectal surgery. Materials and methods All procedures involving anastomoses of the colon or the rectum, which were performed between November 2002 and February 2006 in a single institution, were prospectively entered into a computerized database. Results One thousand eighteen colorectal resections and 811 anastomoses were performed over this 40-month period. The most frequent procedures were sigmoid (276) and right colectomies (217). The overall anastomotic leak rate was 3.8%. The mortality rate associated with anastomotic leak was 12.9%. In univariate analysis, the following parameters were associated with an increased risk for anastomotic dehiscence: (1) ASA score ≥ 3 (p = 0.004), (2) prolonged (>3 h) operative time (p = 0.02), (3) rectal location of the disease (p < 0.001), (4) and a body mass index > 25 (p = 0.04). In multivariate analysis, ASA score ≥ 3 (OR = 2.5; 95% CI 1.5–4.3, p < 0.001), operative time > 3 h [OR = 3.0; 95% CI 1.1–8.0, p = 0.02), and rectal location of the disease (OR = 3.75; 95% CI 1.5–9.0 (vs left colon), p = 0.003; OR = 7.69; 95% CI 2.2–27.3 (vs right colon), p = 0.001] were factors significantly associated with a higher risk of anastomotic dehiscence. Conclusions Three risk factors for anastomotic leak have been identified, one is patient-related (ASA score), one is disease-related (rectal location), the third being surgery-related (prolonged operative time). These factors should be considered in perioperative decision-making regarding defunctioning stoma formation.     

An association analysis of the HLA gene region in latent autoimmune diabetes in adults

Aims/hypothesis Pathophysiological similarities between latent autoimmune diabetes in adults (LADA) and type 1 diabetes indicate an overlap in genetic susceptibility. HLA-DRB1 and HLA-DQB1 are major susceptibility genes for type 1 diabetes but studies of these genes in LADA have been limited. Our aim was to define patterns of HLA-encoded susceptibility/protection in a large, well characterised LADA cohort, and to establish association with disease and age at diagnosis. Materials and methods Patients with LADA (n = 387, including 211 patients from the UK Prospective Diabetes Study) and non-diabetic control subjects (n = 327) were of British/Irish European origin. The HLA-DRB1 and -DQB1 genes were genotyped by sequence-specific PCR. Results As in type 1 diabetes mellitus, DRB1*0301_DQB1*0201 (odds ratio [OR] = 3.08, 95% CI 2.32–4.12, p = 1.2 × 10⁻¹⁶) and DRB1*0401_DQB1*0302 (OR = 2.57, 95% CI 1.80–3.73, p = 4.5 × 10⁻⁸) were the main susceptibility haplotypes in LADA, and DRB1*1501_DQB1*0602 was protective (OR = 0.21, 95% CI 0.13–0.34, p = 4.2 × 10⁻¹³). Differential susceptibility was conferred by DR4 subtypes: DRB1*0401 was predisposing (OR = 1.79, 95% CI 1.35–2.38, p = 2.7 × 10⁻⁵) whereas DRB1*0403 was protective (OR = 0.37, 95% CI 0.13–0.97, p = 0.033). The highest-risk genotypes were DRB1*0301/DRB1*0401 and DQB1*0201/DQB1*0302 (OR = 5.14, 95% CI 2.68–10.69, p = 1.3 × 10⁻⁸; and OR = 6.88, 95% CI 3.54–14.68, p = 1.2 × 10⁻¹¹, respectively). These genotypes and those containing DRB1*0401 and DQB1*0302 associated with a younger age at diagnosis in LADA, whereas genotypes containing DRB1*1501 and DQB1*0602 associated with an older age at diagnosis. Conclusions/interpretation Patterns of susceptibility at the HLA-DRB1 and HLA-DQB1 loci in LADA are similar to those reported for type 1 diabetes, supporting the hypothesis that autoimmune diabetes occurring in adults is an age-related extension of the pathophysiological process presenting as childhood-onset type 1 diabetes. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible to authorised users.     

Risk factors for mortality–morbidity after emergency–urgent colorectal surgery

Background  The aim of this study was to assess the risk factors associated with mortality and morbidity following emergency or urgent colorectal surgery. Materials and methods  All data regarding the 462 patients who underwent emergency colonic resection in our institution between November 2002 and December 2007 were prospectively entered into a computerized database. Results  The median age of patients was 73 (range 17–98) years. The most common indications for surgery were: 171 adenocarcinomas (37%), 129 complicated diverticulitis (28%), and 35 colonic ischemia (7.5%). Overall mortality and morbidity rates were 14% and 36%, respectively. In multivariate analysis, the only parameter significantly associated with postoperative mortality was blood loss >500 cm³ (odds ratio (OR) = 3.33, 95% confidence interval (CI) 1.63–6.82, p = 0.001). There were three parameters which correlated with postoperative morbidity: ASA score ≥3 (OR = 2.9, 95% CI 1.9–4.5, p < 0.001), colonic ischemia (OR = 3.4, 95% CI 1.4–7.7, p = 0.006), and stoma creation (OR = 2.2, 95% CI 1.4–3.4, p = 0.0003). Conclusions  The main risk factors for postoperative morbidity and mortality following emergency colorectal surgery are related to: (1) patients’ ASA score, (2) colonic ischemia, and (3) perioperative bleeding. These variables should be considered in the elaboration of future scoring systems to predict outcome of emergency colorectal surgery.     

CTLA4 exon1 A49G polymorphism in Slovak patients with rheumatoid arthritis and Hashimoto thyroiditis—results and the review of the literature

Autoimmune thyroid diseases frequently overlaps with rheumatoid arthritis (RA). Among genetic factors, the role of the HLA antigens and CTLA4 gene polymorphisms in the overlapping has been suggested. The aim of this study was to investigate the alleles and genotypes frequency of the CTLA4 exon1 A49G polymorphism in Slovak patients with RA, Hashimoto thyroiditis (HT), both (RA + HT) and in healthy controls. Fifty-seven unrelated adults with RA, 57 patients with HT, 34 patients with both (RA + HT), and 51 normal subjects were studied. All were ethnic Slovaks living in the same geographical area. The CTLA4 exon1 A49G polymorphism was genotyped by using small amplicon melting analysis after real-time PCR. The CTLA4 49GG genotype and G allele frequency in the group with RA was not significantly higher in comparison with controls (10.53% vs. 9.8%, p = 0.62, OR 1.39, 95% CI 0.35–5.74 and 39.47% vs. 34.31%, p = 0.43, OR 1.25, 95% CI 0.72–2.18). The frequency of GG genotype was slightly but not significantly higher in patients with HT as compared with control group (19.3% vs. 9.8%, p = 0.17, OR 2.27, 95% CI 0.67–8.45). However, the frequency of GG genotype and G allele in patients with both RA and HT was significantly higher than that in controls (29.41% vs. 9.8%, p = 0.02, OR 4.49, 95% CI 1.20–18.54 and 51.47% vs. 34.31%, p = 0.03, OR 2.02, 95% CI 1.08–3.81). The frequency of GG genotype of CTLA4 A49G gene polymorphism in Slovak patients with RA is not significantly higher in comparison to control group. However, carriers of GG genotype with RA may be susceptible to develop HT.     

Community Volunteerism of US Physicians

Background  Many physicians and professional leaders agree that community participation is an important professional role for physicians. Volunteerism has also received increasing attention in the national agenda for social change. Yet little is known about physicians’ community volunteer activities. Objective  To measure levels of community volunteerism among US physicians. Design and Participants  Analysis of the 2003 Current Population Survey (CPS) Volunteer Supplement, a cross-sectional, nationally-representative, in-person and telephone survey of 84,077 adult citizens, including 316 physicians. Measurements  The primary outcome was whether the respondent had volunteered in the prior 12 months and if so the total number of hours. The level of community volunteer activity was compared between physicians, lawyers and the general public. In addition, predictors of physician volunteerism were identified. Results  According to the survey, 39% of physicians had volunteered in their community in the past 12 months compared to 30% of the general public (p = 0.002) and 57% of lawyers (p < 0.001). After multivariate adjustment, physicians were half as likely as the general public (OR = 0.52, p < 0.001) or lawyers (OR = 0.44, p < 0.001) to have volunteered. Physicians were more likely to have volunteered if they worked part-time (OR = 3.35, p = 0.03), variable hours (OR = 3.16, p = 0.03), or between 45–54 hours per week (OR = 3.15, p = 0.02) compared to a 35–44 hour work week. Conclusions  Despite highly favorable physician attitudes toward volunteerism in prior surveys, less than half of US physicians have volunteered with community organizations in the past year. Renewed attention to understanding and increasing physician engagement in community volunteer work is needed.     

Accelerated atrophy of lower leg and foot muscles—a follow-up study of long-term diabetic polyneuropathy using magnetic resonance imaging (MRI)

Aims/hypothesis  The aim of the study was to determine the loss of muscle volume in the lower leg and foot in long-term diabetic patients in relation to the presence of neuropathy. Methods  We re-examined 26 type 1 diabetic patients who had participated in magnetic resonance imaging (MRI) studies on muscle volume in the lower leg and foot 9 to 12 years earlier. Re-examination involved MRI, isokinetic dynamometry, clinical examination, electrophysiological studies and quantitative sensory examinations. Results  Annual loss of muscle volume of ankle dorsal and plantar flexors was 4.5 (5.5–3.9)% (median [range]) and 5.0 (7.0–4.2)% in neuropathic patients, 1.9 (3.2–1.0)% and 1.8 (2.6–1.3)% in non-neuropathic patients, and 1.7 (2.8–0.8)% and 1.8 (2.4–0.8)% in controls, respectively (p < 0.01). Annual change of volume and strength correlated for ankle dorsal flexors (r _s = 0.73, p < 0.01) and for ankle plantar flexors (r _s = 0.63, p < 0.05) in diabetic patients. In addition, annual change of muscle volume for dorsal and plantar flexors was related to the combined score of all measures of neuropathy (r _s = −0.68, p < 0.02 and r _s = −0.73, p < 0.01, respectively). Foot muscle volume declined annually by 3.0 (3.4–1.0)% in neuropathic patients and by 1.1 (4.0–0.2)% in non-neuropathic patients, both values being significantly different from controls (0.2 [−2.5 to 2.4]%). Loss of foot muscle volume was related to severity of neuropathy assessed at clinical evaluation (r _s = −0.6, p < 0.05). Conclusions/interpretation  Muscular atrophy in long-term diabetic neuropathy occurs early in the feet, progresses steadily in the lower legs, relates to severity of neuropathy and leads to weakness at the ankle. An erratum to this article can be found at     

Caspase-3 activity, response to chemotherapy and clinical outcome in patients with colon cancer

Background and aims The prognostic value of the degree of apoptosis in colorectal cancer is controversial. This study evaluates the putative clinical usefulness of measuring caspase-3 activity as a prognostic factor in colonic cancer patients receiving 5-fluoracil adjuvant chemotherapy. Materials and methods We evaluated caspase-3-like protease activity in tumours and in normal colon tissue. Specimens were studied from 54 patients. These patients had either stage III cancer (Dukes stage C) or high-risk stage II cancer (Dukes stage B2 with invasion of adjacent organs, lymphatic or vascular infiltration or carcinoembryonic antigen [CEA] > 5). Median follow-up was 73 months. Univariate analysis was performed previously to explore the relation of different variables (age, sex, preoperative CEA, tumour size, Dukes stage, vascular invasion, lymphatic invasion, caspase-3 activity in tumour and caspase-3 activity in normal mucosa) as prognostic factors of tumour recurrence after chemotherapy treatment. Subsequently, a multivariate Cox regression model was performed. Results Median values of caspase-3 activity in tumours were more than twice those in normal mucosa (88.1 vs 40.6 U, p = 0.001), showing a statistically significant correlation (r = 0.34). Significant prognostic factors of recurrence in multivariate analysis were: male sex (odds ratio, OR = 3.53 [1.13–10.90], p = 0.02), age (OR = 1.09 [1.01–1.18], p = 0.03), Dukes stage (OR = 1.93 [1.01–3.70]), caspase-3 activity in normal mucosa (OR = 1.02 [1.01–1.04], p = 0.017) and caspase-3 activity in tumour (OR = 1.02 [1.01–1.03], p = 0.013). Conclusion Low caspase-3 activity in the normal mucosa and tumour are independent prognostic factors of tumour recurrence in patients receiving adjuvant 5-fluoracil-based treatment in colon cancer, correlating with poor disease-free survival and higher recurrence rate.     

Midlife muscle strength and human longevity up to age 100 years: a 44-year prospective study among a decedent cohort

We studied prospectively the midlife handgrip strength, living habits, and parents’ longevity as predictors of length of life up to becoming a centenarian. The participants were 2,239 men from the Honolulu Heart Program/Honolulu–Asia Aging Study who were born before the end of June 1909 and who took part in baseline physical assessment in 1965–1968, when they were 56–68 years old. Deaths were followed until the end of June 2009 for 44 years with complete ascertainment. Longevity was categorized as centenarian (≥100 years, n = 47), nonagenarian (90–99 years, n = 545), octogenarian (80–89 years, n = 847), and ≤79 years (n = 801, reference). The average survival after baseline was 20.8 years (SD = 9.62). Compared with people who died at the age of ≤79 years, centenarians belonged 2.5 times (odds ratio (OR) = 2.52, 95% confidence interval (CI) = 1.23–5.10) more often to the highest third of grip strength in midlife, were never smokers (OR = 5.75 95% CI = 3.06–10.80), had participated in physical activity outside work (OR = 1.13 per daily hour, 95% CI = 1.02–1.25), and had a long-lived mother (≥80 vs. ≤60 years, OR = 2.3, 95% CI = 1.06–5.01). Associations for nonagenarians and octogenarians were parallel, but weaker. Multivariate modeling showed that mother’s longevity and offspring’s grip strength operated through the same or overlapping pathway to longevity. High midlife grip strength and long-lived mother may indicate resilience to aging, which, combined with healthy lifestyle, increases the probability of extreme longevity.     

Overcoming Poor Attendance to First Scheduled Colonoscopy: A Randomized Trial of Peer Coach or Brochure Support

OBJECTIVES Among patients unlikely to attend a scheduled colonoscopy, we examined the impact of peer coach versus educational brochure support and compared these with concurrent patients who did not receive support. METHODS From health system data, we identified 275 consecutive patients aged >50 who kept <75% of visits to 4 primary care practices and scheduled for a first colonoscopy from February 1, 2005 to August 31, 2006. Using block randomization, we assigned consenting patients to a phone call by a peer coach trained to address barriers to attendance or to a mailed colonoscopy brochure. Study data came from electronic medical records. Odds ratios of colonoscopy attendance were adjusted for demographic, clinical, and health care factors. RESULTS Colonoscopy attendance by the peer coach group (N = 70) and brochure group (N = 66) differed by 11% (68.6% vs 57.6%, respectively). Compared with the brochure group, the peer coach group had over twofold greater adjusted odds ratio (AOR) of attendance (2.14, 95% confidence interval [CI] = 0.99–4.63) as did 49 patients who met the prespecified criteria for needing no support (2.68, 95%CI = 1.05–6.82) but the AORs did not differ significantly for 41 patients who declined support (0.61, 95%CI = 0.25–1.45) and 49 patients who could not be contacted (0.85, 95%CI = 0.36–2.02). Attendance was less likely for black versus white race (AOR = 0.37, 95%CI = 0.19–0.72) but more likely for patients with high versus low primary care visit adherence (AOR = 2.30, 95%CI = 1.04–5.07). CONCLUSION For patients who often fail to keep appointments, peer coach support appears to promote colonoscopy attendance more than an educational brochure. Presented at the 30th Annual Meeting of the Society of General Internal Medicine, Toronto, Ontario, April 26, 2007.     

Endothelial nitric oxide synthase T-786C polymorphism in rheumatoid arthritis: association with extraarticular manifestations

Several genetic factors were implicated in the pathogenesis of rheumatoid arthritis (RA). A case–control study was carried out to verify the associations of T-786C polymorphism in the promoter region of the endothelial nitric oxide synthase (eNOS) gene with RA. One hundred and five consecutive RA patients and 100 healthy controls were genotyped. The distribution of the T-786C genotype and alleles did not differ significantly between RA patients and controls. Nevertheless, the frequency of extraarticular manifestations was significantly greater among the carriers of the C/C genotype than among carriers of the T/C and T/T genotypes (P = 0.022). The C/C genotype was significantly associated with extraarticular manifestations compared with the T/T and T/C genotypes taken together (OR = 4.9, 95% CI = 1.3–18.9). The C allele was significantly associated with extraarticular manifestations of RA (P _corr = 0.032). The results suggested the existence of an association between the T-786C polymorphism of the eNOS gene and extraarticular manifestations of RA.     

The diagnostic utility of the anti-CCP antibody test is no better than rheumatoid factor in South Africans with early rheumatoid arthritis

To establish the diagnostic utility of the anti-cyclic-citrullinated peptide antibody (aCCP) test in Black South Africans with early rheumatoid arthritis (RA). A cross-sectional study comparing the rheumatoid factor (RF) and aCCP status in RA patients and a control group consisting of healthy subjects, and patients with systemic lupus erythematosus (SLE) and scleroderma. The sensitivity, specificity, positive (PPV) and negative predictive values of the aCCP test alone were 82.5%, 84.9%, 87.6% and 79% versus 81.7%, 90.7%, 92.5% and 78% for RF alone. The best specificity (95.3) and PPV (95.8%) was observed when both aCCP and RF tests were positive. Patients with erosive disease had a significantly higher mean RF titre compared with those with non-erosive disease (p = 0.007). There was a trend towards an association of smoking (OR = 4.1, 95% CI = 0.9–18.6) and functional disability (p = 0.07) with RF-positive status. No similar clinical associations were observed with aCCP. Almost a third of SLE patients were aCCP positive. Despite the best specificity and PPV observed when both the aCCP and RF tests were positive, our findings suggest that testing for aCCP is only cost-effective in the RF-negative patient in whom there is a strong clinical suspicion of RA.     

Association of IL-18 gene polymorphism (?137C) with arthritis manifestations in SLE: combined effect with IFN gamma gene polymorphism (+874A)

We analyzed the association between single nucleotide polymorphisms in IL-12 and IL-18 genes in disease susceptibility and severity of SLE in Thais. A weak association was observed between A allele of the IL-12 gene at the 3′ untranslated region in SLE patients with proteinuria (OR = 1.89, 95% CI = 1.05–3.40, P = 0.02, Pc = 0.06). In addition, we found a significant association between C allele of IL-18 (−137) with arthritis (OR = 6.88, 95% CI = 1.54–42.93, P = 0.003, Pc = 0.009). The presence of one C allele (C/C+C/G) was associated with significant OR of 8.72 (95% CI = 1.83–56.71, P = 0.001, Pc = 0.003). Interestingly, we found the combined effect between the G/C genotype of IL-18 (−137) and the A/A genotype of IFNG (+874) gene causing susceptibility of arthritis in SLE patients (OR = 13.22, 95% CI = 1.56–291.66, P = 0.004).