Anti-inflammatory effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: potential benefits for the prevention of atrial fibrillation: reply

We thank Drs Liu and Li for their interest in our randomizedtrial investigating the anti-arrhythmic effect of perindopriland losartan in the setting of lone paroxysmal atrial fibrillation(AF). While agreeing on modification of atrial remodelling asthe     

Carpal tunnel syndrome presenting as a non-healing ulcer.

Skin ulceration in carpal tunnel syndrome is rare. A case report of a non-healing ulcer due to carpal tunnel with severe sensorimotor denervation is presented and discussed.     

Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal.

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD.     

A Comparison of Depressive Symptoms in Stroke and Primary Care: Applying Rasch Models to Evaluate the Center for Epidemiologic Studies-Depression Scale

OBJECTIVES: Clinical trials and community-based studies often include the Center for Epidemiologic Studies-Depression scale (CES-D) as a measure of depression outcome. We compared responses to symptom-related items on the CES-D by depressed stroke and primary-care patients for several purposes: 1) to illustrate the use of Item Response Theory (IRT)-based (Rasch) models for comparing scale functioning across different patient subgroups; and 2) to inform clinicians and outcome researchers about scale functioning and depressive symptomatology in stroke- compared with primary care-based depression. METHODS: Two data sources were analyzed, including 32 depressed patients who were 3 months poststroke, and 366 depressed primary-care patients. Presence of depression was based on a CES-D score 16 or higher. Rasch models were used to assess item fit and compare item hierarchies between depressed primary-care and stroke patients. RESULTS: Item hierarchies were similar for poststroke depression and primary care-based depression. Interpersonal disruption items were the most difficult to endorse for both groups. No items misfit the scale in primary-care depression. Items relating to restless sleep, unfriendliness, and crying slightly misfit the scale in stroke patients, that is, may measure a different trait. Differential item functioning (DIF) between the groups was identified for items relating to appetite, restless sleep, crying, and feeling disliked. CONCLUSIONS: Results generally supported the use of the CES-D as measure of depression outcome, particularly in primary care-based depression. DIF may imply that slightly different clusters of depressive symptoms are reported by depressed stroke patients compared with primary care, but this is conjectural given the small stroke sample size and the same items have been previously associated with bias in studies of large nonstroke samples. This study found Rasch models to be useful tools to investigate scale performance for different clinical applications.     

Identification and characterization of linear B-cell epitopes of beta-globulin, a major allergen of sesame seeds

BACKGROUND: The increased consumption of foods containing sesame seeds is paralleled by an increase in reported sesame-induced allergic reactions. OBJECTIVE: This study aimed at identifying and characterizing the linear B-cell epitopes of the 14-kd beta-globulin, the major allergen of sesame seed. METHODS: A peptide containing 71 amino acids (peptide B) was previously identified by us as the IgE-binding region on beta-globulin. To determine the amino acid sequence of the IgE-binding sites on peptide B, we synthesized overlapping peptides 20 and 10 amino acid residues long that span the entire length of peptide B, which were offset from each other by 10 and 2 amino acid residues, respectively. Sera from 20 subjects given diagnoses of allergy to sesame beta-globulin served to identify the epitopes by using the dot-blot test. RESULTS: At least 9 different IgE-recognition sites were identified on peptide B. Three of them, numbers 2, 3, and 13 (corresponding to amino acids 46-55, 48-57, and 76-86, respectively, in the beta-globulin sequence), appeared to be immunodominant IgE-binding epitopes. Also, these peptides were best recognized in terms of intensity of response. There was no obvious sequence motif shared by the 9 different IgE-binding epitopes of beta-globulin. However, approximately 60% of the amino acids represented in the epitopes are hydrophobic residues. CONCLUSION: Identification of the IgE-binding epitopes might provide a better understanding of the functional role the allergens play in the disease and might have implications for immunodiagnosis and probably immunotherapy.     

Conceptual and methodologic challenges of assessing the short-term efficacy of Guggulu in obesity: data emergent from a naturalistic clinical trial

An open comparative trial was conducted in 58 adult obese patients (Body Mass Index > or = 25 kg/square metre). Group I (n = 27), non-drug, was advised diet (1200-1600 cals) and a brisk walk for 30 minutes. Group II, in addition, received Guggulu (Medohar) 1.5-3 gms/day for 30 days. Mean difference in weight loss between Guggulu and non-drug group was 0.32 kg (ns) on day 15 and 0.58 kg on day 30 (ns). The mean weight reduction in patients (> 90 kgs) was 1.92 kg (ns) and 2.25 kg (ns) higher in Guggulu group. All patients weighing > 90 kg lost weight in Guggulu group whilst 3 in non-drug group did not lose weight. Guggulu was tolerated well. The data from this pilot study suggest a synergistic diet-Guggulu interaction over 30 days in patients weighing > 90 kgs which needs to be confirmed in a large placebo controlled study.     

Serum beta2-microglobulin and immunoglobulin levels in young hemodialysis patients

 Amyloidosis is a complication of long-term hemodialysis treatment. The major histological feature of hemodialysis-associated amyloidosis (HAA) is the deposition of amyloid fibrils in the affected lesions, due, in part, to elevated serum β₂-microglobulin (β2M) levels. In vitro studies reveal that serum immunoglobulin light and heavy chains co-deposit with β2M in tissues affected by HAA. Only one study of HAA has been performed in young dialysis patients. We therefore assessed risk factors for HAA in a group (n=30) of young (18.7±0.9 years) patients receiving chronic, uninterrupted hemodialysis using cellulose acetate membranes. All patients initiated dialysis before reaching 18 years of age. The pre-dialysis serum β2M level was 49.7±3.9 mg/l (normal 0–2.4 mg/l). Since serum albumin was normal (4.3±0.1 mg/dl) and serum protein/albumin was elevated (1.7±0.0, normal 1.2–1.5), indicating increased circulating protein, we assayed immunoglobulins in the same patients. The serum immunoglobulin levels (expressed as a percentage of the total level of serum proteins) were elevated (21.3±0.9%, normal 11.1%–21.0%). The Kt/v was 1.37±0.03, suggesting that the high levels of serum β2M and immunoglobulins were not due to inadequate dialysis in these patients. Patients with residual renal function (Kr) did display significantly lower serum levels of β2M (33.2±2.3, P=0.03). Furthermore, improved clearance of β2M correlated with higher values of Kr (r=0.914). In contrast, serum levels of immunoglobulin (22.6±3.7, P=0.5) were unaffected by Kr. In addition, there was no correlation between older age at onset of dialysis and serum levels of either β2M (r=0.107) or immunoglobulins (r=0.321). Finally, the length of time on dialysis had no effect on serum levels of either β2M (r=0.105) or immunoglobulins (r=0.092). Taken together, these results indicate that young hemodialysis patients may be at risk for HAA. Received: 13 January 1998 / Revised: 1 June 1998 / Accepted: 2 June 1998     

Estriol ameliorates autoimmune demyelinating disease: implications for multiple sclerosis

OBJECTIVE: To evaluate the use of estriol in the treatment of experimental autoimmune encephalomyelitis (EAE) and other cell mediated autoimmune diseases. BACKGROUND: Experimental autoimmune encephalomyelitis is a T helper 1 (Th1)-mediated autoimmune demyelinating disease that is a useful model for the study of immune responses in MS. Interestingly, both EAE and MS have been shown to be ameliorated during late pregnancy. METHODS: Estriol, progesterone, and placebo pellets were implanted in mice during the effector phase of adoptive EAE. Disease scores were compared between treatment groups, and autoantigen-specific humoral and cellular responses were examined. RESULTS: Estriol treatment reduced the severity of EAE significantly compared with placebo treatment whereas progesterone treatment had no effect. Estriol doses that induced serum estriol levels that approximated estriol levels during late pregnancy were capable of ameliorating disease. Estriol-treated EAE mice had significantly higher levels of serum antibodies of the immunoglobulin (Ig) G1 isotype specific for the autoantigen myelin basic protein (MBP). Further, MBP-specific T-lymphocyte responses from estriol-treated EAE mice were characterized by significantly increased production of the Th2 cytokine interleukin 10 (IL-10). T lymphocytes were shown to be the primary source of IL-10 within antigen-stimulated splenocyte populations. CONCLUSIONS: Estriol as a hormone involved in immune changes during pregnancy may provide a basis for the novel therapeutic use of estriol for MS and other putative Th1-mediated autoimmune diseases that improve during late pregnancy.