Charlson Co‐morbidity Index and albumin significantly associated with fracture risk in peritoneal dialysis patients

Published literature on fracture in dialysis patients seldom addressed the effect of co‐morbidity and malnutrition. In this study, we reported the incidence and risk factors for fracture in peritoneal dialysis patients. Peritoneal dialysis patients who had fractures between 2006 and 2011 were recruited. Demographic data, details of fracture, Charlson Co‐morbidity Index (CCI) and biochemical parameters were also collected. Non‐fracture controls, matched for age, gender and duration of dialysis, were also recruited at ratio 1:1 for fracture risk analysis. The incidence of fracture was 1 in 37 patient‐years. The commonest site of fracture was neck of femur (n = 16, 55.2%). Twenty‐four patients (82.8%) developed fracture after slip and fall injury. Eight out of 17 self‐ambulatory patients (47.1%) became non‐ambulatory after fracture. Infection was the commonest complication during hospitalization. Univariant analysis demonstrated high CCI (P = 0.001), hypoalbuminaemia (P < 0.001), loss of self autonomy (P = 0.006) and non‐ambulatory state (P = 0.011) significantly associated with increased fracture risk. However, only CCI (odds ratio (OR) 1.373, P = 0.028) and albumin (OR 0.893, P = 0.025) increased fracture risk significantly on multivariant analysis. Bone profile and parathyroid hormone were not significant risk factors. To conclude, fracture associated with adverse outcome in peritoneal dialysis patients. High CCI score and hypoalbuminaemia significantly increase risk of fracture.     

A case of crossed aphasia with apraxia of speech

Apraxia of speech (AOS) is a rare, but well-defined motor speech disorder. It is characterized by irregular articulatory errors, attempts of self-correction and persistent prosodic abnormalities. Similar to aphasia, AOS is also localized to the dominant cerebral hemisphere. We report a case of Crossed Aphasia with AOS in a 48-year-old right-handed man due to an ischemic infarct in right cerebral hemisphere.     

Clinical profile of psychogenic non-epileptic seizures in adults: A study of 63 cases

Aims:

To evaluate clinical profile and short-term outcome of psychogenic non-epileptic seizures (PNES) in Indian adult population.

Setting and Design:

A prospective observational study, conducted at tertiary teaching institute at New Delhi.

Materials and Methods:

Sixty-three patients with confirmed PNES were enrolled. The diagnosis was based on witnessing the event during video-electroencephalography (Video-EEG) monitoring. A detailed clinical evaluation was done including evaluation for coexistent anxiety or depressive disorders. Patients were divided into two groups on the basis of excessive or paucity of movements during PNES attacks. Patients were followed-up to 12 months for their PNES frequency.

Statistical Analysis:

Means and standard deviations were calculated for continuous variables. Chi-square and Students t-test were used to compare categorical and continuous variables respectively.

Results:

The mean age at onset of PNES was 25.44 years; with F:M ratio of 9.5:1. Coexistent epilepsy was present in 13 (20.63%) cases. Twenty-two patients (44%) with only PNES (n = 50) had received antiepileptic drugs. Out of 63 patients of PNES 24 (38.1%) had predominant motor phenomenon, whereas 39 (61.9%) had limp attacks. The common features observed were pre-ictal headache, ictal eye closure, jaw clenching, resistant behavior, ictal weeping, ictal vocalization, and unresponsiveness during episodes. Comorbid anxiety and depressive disorders was seen in 62.3% and 90.16% patients, respectively. Short-term (6-12 months) outcome of 45 patients was good (seizure freedom in 46.66% and >50% improvement in 24.44% cases).

Conclusion:

PNES is common, but frequently misdiagnosed and treated as epileptic seizures. A high index of suspicion is required for an early diagnosis. Proper disclosure of diagnosis and management of the psychiatric comorbidities can improve their outcome.

Limitation:

Limited sample size and change in seizures frequency as the only parameter for the assessment of the outcome are the two major limitations of our study.     

A hexanucleotide repeat upstream of eotaxin gene promoter is associated with asthma, serum total IgE and plasma eotaxin levels

Background

Eotaxin (CCL11) is a small protein produced in the lungs of patients with asthma, and is a potent chemoattractant for eosinophils.

Aim

To elucidate the role of eotaxin in asthma by an association study of functional and novel eotaxin polymorphisms in case–control and family‐based study designs.

Methods

Eotaxin +67G/A, –384A/G and –426C/T single‐nucleotide polymorphisms and a hexanucleotide (GAAGGA)_n repeat 10.9 kb upstream of the gene were genotyped in a cohort of age, sex and ethnically matched patients with asthma (n = 235) and healthy controls (n = 239), and also in a study population of 230 families with asthma recruited from north/northwest India. Total serum IgE (TsIgE) and plasma eotaxin levels were measured using ELISA.

Results

+67G/A polymorphism was found to be significantly associated with asthma in case–control (p = 0.009) and family‐based studies (p = 0.006). Its functional role, as it was correlated with plasma eotaxin levels (p = 0.006), was also demonstrated. Further, –384C/T single‐nucleotide polymorphism was found to be significantly associated with log₁₀ TsIgE (p = 0.016 in case–control and p = 0.018 in families) and eotaxin levels (p = 0.007). Most interestingly, for the first time, a highly significant association of the newly studied (GAAGGA)_n hexanucleotide repeat with asthma (p = 3×10⁻⁶), log₁₀TsIgE (p = 0.006) and eotaxin levels (p = 0.004) was observed. G_A_C_8 was also identified as an important risk haplotype associated with high TsIgE and plasma eotaxin levels.

Conclusions

This study provides further evidence that eotaxin polymorphisms are associated with the development of asthma by regulating eotaxin levels and reinforces towards the scanning of other chemokine genes present at 17q21 locus for their association with asthma and related phenotypes.Eosinophils play a major role in the pathogenesis of allergic diseases including asthma by releasing various granular proteins, reactive NO, cytokines and chemokines at the site of inflammation, thus causing tissue damage.¹ Interplay between chemokines and their receptors are considered to be crucial for the trafficking of eosinophil and other lymphocytes from the circulation to the bronchoalveolar spaces of the patients with asthma.² Eotaxin (chemokine, CC motif, ligand; CCL11) is a predominant eosinophil chemoattractant, which binds to chemokine receptor 3.^3,4 Chemokine receptor 3 is also present on the Th2 CD4⁺ lymphocytes, basophils, dendritic cells and mast cells.^5,6 Thus, the role of eotaxin in asthma is not confined to eosinophil migration and activation only, but extended to many other effector cells involved in disease pathogenesis. It has also been observed that along with interleukin 5, eotaxin prolongs the viability of eosinophils.⁷ Eotaxin mRNA and protein are found to be elevated in the induced sputum, bronchial epithelium and airways of the patients with moderate to severe asthma.^8,9,10 Bronchoalveolar lavage fluid of the patients with asthma also showed increased levels of eotaxin after allergen inhalation.¹¹ In addition, higher plasma eotaxin levels have been observed in subjects with symptoms of acute asthma and airflow obstruction than subjects with stable asthma. Plasma eotaxin levels have been correlated with severity of asthma even in the presence of steroid treatment.^12,13Eotaxin gene is present on chromosome 17q21.1, where linkage with asthma and related phenotypes has been previously reported in various ethnic populations.^14,15 Previous studies on eotaxin gene polymorphisms and asthma remain inconclusive as most of them failed to establish a strong association.^{16,17,18,19,20} However, in few other studies, eotaxin single‐nucleotide polymorphisms (SNPs) have been correlated significantly with asthma‐associated phenotypes including lung function, serum IgE, circulating blood eosinophils, eosinophil migration and activation, and plasma eotaxin levels.^{16,17,18,21,22} Studies have also been undertaken to demonstrate the functional implication of various promoter and exonic variants of the eotaxin.^20,22 Notably, the variant and the direction of association are inconsistent across different ethnic populations owing to some inherent reasons. However, no such studies have yet been undertaken in an ethnically divergent Indian population.Importantly, the 17q11–17q21 chromosomal region harbours many other important chemokines including RANTES, MCP1, MCP3 and so on, and also the gene for inducible nitric oxide synthase. Recently, we have reported the association of the gene for inducible nitric oxide synthase microsatellite repeats with asthma and related phenotypes in an Indian population, demonstrating the importance of 17q region in asthma predisposition.²³ The results of our previous study and the well‐documented role of eotaxin in asthma prompted us to undertake an association study of eotaxin gene with asthma and associated phenotypes in case–control and family‐based study designs. We have also measured the plasma eotaxin level and attempted to correlate it with eotaxin gene variants.     

Pancreatic islets engineered with a FasL protein induce systemic tolerance at the induction phase that evolves into long‐term graft‐localized immune privilege

We have previously shown that pancreatic islets engineered to transiently display a modified form of FasL protein (SA‐FasL) on their surface survive indefinitely in allogeneic recipients without a need for chronic immunosuppression. Mechanisms that confer long‐term protection to allograft are yet to be elucidated. We herein demonstrated that immune protection evolves in two distinct phases; induction and maintenance. SA‐FasL‐engineered allogeneic islets survived indefinitely and conferred protection to a second set of donor‐matched, but not third‐party, unmanipulated islet grafts simultaneously transplanted under the contralateral kidney capsule. Protection at the induction phase involved a reduction in the frequency of proliferating alloreactive T cells in the graft‐draining lymph nodes, and required phagocytes and TGF‐β. At the maintenance phase, immune protection evolved into graft site‐restricted immune privilege as the destruction of long‐surviving SA‐FasL‐islet grafts by streptozotocin followed by the transplantation of a second set of unmanipulated islet grafts into the same site from the donor, but not third party, resulted in indefinite survival. The induced immune privilege required both CD4⁺CD25⁺Foxp3⁺ Treg cells and persistent presence of donor antigens. Engineering cell and tissue surfaces with SA‐FasL protein provides a practical, efficient, and safe means of localized immunomodulation with important implications for autoimmunity and transplantation.     

Sevoflurane for trans-sternal thymectomy in myasthenia gravis

Myasthenic gravis (MG) is an autoimmune disease associated with acetylcholine receptor deficiency. Patients with MG exhibit increased sensitivity to non-depolarising muscle relaxants. In an attempt to avoid neuromuscular blockers, we used sevoflurane in two myasthenic patients undergoing trans-sternal thymectomy. Inhalation of 8% sevoflurane in oxygen using vital capacity technique produced rapid, pleasant and smooth induction and provided good tracheal intubating conditions. In both patients anaesthesia was maintained with 1.5-2% end-tidal concentration of sevoflurane and nitrous oxide in oxygen without adjunctive neuromuscular blocking agents. There were minimal changes in cardiovascular variables and recovery was faster. It is suggested that sevoflurane may be the main anaesthetic for both induction and maintenance in myasthenic patients undergoing trans-sternal thymectomy.