Multi-minicore disease: a rare form of myopathy

BACKGROUND: Multi-minicore disease is a rare form of myopathy characterized by slowly progressive or nonprogressive muscle weakness and characteristic multiple cores within the muscle fibers. To the best of our knowledge, this is first documentation of the clinicopathological features of this rare entity from India. MATERIALS AND METHODS: A ll cases of multi-minicore disease diagnosed in our laboratory were retrieved. Clinical and pathological features were reviewed. RESULT: During a period of two years (January 2004 to December 2005), we received 985 muscle biopsies for various reasons. Of which, 15 were diagnosed as myopathies and four of which were of multi-minicore disease. Thus, multi-minicore disease comprises 0.40% of all muscle diseases and 26.6% of all myopathies. All were male and presented in early childhood (first decade of life) with generalized hypotonia and muscle weakness. All of them had dysmorphic facies and three had high arched palate. CPK levels were normal and EMG was myopathic except in one patient. Microscopic examination revealed minimal changes with Type I fibers' predominance but characteristic multiple cores in the myofibers. Ultrastructural examination showed both structured and unstructured cores. CONCLUSIONS: Multi-minicore disease, although a rare form of myopathies, should be suspected in children who present with generalized hypotonia and slowly progressive muscle weakness along with dysmorphic facies.     

Occipitocervical contoured rod stabilization: does it still have a role amidst the modern stabilization techniques?

Background: The occipitocervical contoured rod (CR) stabilization for use in craniovertebral junction (CVJ) pathologies is an effective and economical technique of posterior fusion (PF). Aims: The various indications for CR in CVJ pathologies are discussed. Settings and Design: Retrospective analysis. Materials and Methods: Fifty-four patients (mean age: 31.02 +/- 13.44 years; male: female ratio=5.75:1) who underwent CR stabilization are included. The majority had congenital atlantoaxial dislocation (AAD; n=50); two had CVJ tuberculosis; one each had rheumatoid arthritis and C2-3 listhesis, respectively. The indications for CR fusion in congenital AAD were associated Chiari 1 malformation (C1M) (n=29); occipitalized C1 arch and/or malformed or deficient C1 or C2 posterior elements (n=9); hypermobile AAD (n=2); and, rotatory AAD (n=3). Contoured rod as a revision procedure was also performed in seven patients. Most patients were in poor grade (18 in Grade III [partial dependence for daily needs] and 15 in Grade IV [total dependence]); 15 patients were in Grade II [independent except for minor deficits] and six in Grade I [no weakness except hyperreflexia or neck pain]. Results: Twenty-four patients improved, 18 stabilized and six deteriorated at a mean follow-up (FU) of 17.78 +/- 19.75 (2-84) months. Six patients were lost to FU. In 37 patients with a FU of at least three months, stability and bony union could be assessed. Thirty-one of them achieved a bony fusion/ stable construct. Conclusions: Contoured rod is especially useful for PF in cases of congenital AAD with coexisting CIM, cervical scoliosis, sub-axial instability and/or asymmetrical facet joints. In acquired pathologies with three-column instability, inclusion of joints one level above the affected one by using CR, especially enhances stability.     

PapA1 and PapA2 are acyltransferases essential for the biosynthesis of the Mycobacterium tuberculosis virulence factor sulfolipid-1

Mycobacterium tuberculosis produces numerous exotic lipids that have been implicated as virulence determinants. One such glycolipid, Sulfolipid-1 (SL-1), consists of a trehalose-2-sulfate (T2S) core acylated with four lipid moieties. A diacylated intermediate in SL-1 biosynthesis, SL(1278), has been shown to activate the adaptive immune response in human patients. Although several proteins involved in SL-1 biosynthesis have been identified, the enzymes that acylate the T2S core to form SL(1278) and SL-1, and the biosynthetic order of these acylation reactions, are unknown. Here we demonstrate that PapA2 and PapA1 are responsible for the sequential acylation of T2S to form SL(1278) and are essential for SL-1 biosynthesis. In vitro, recombinant PapA2 converts T2S to 2'-palmitoyl T2S, and PapA1 further elaborates this newly identified SL-1 intermediate to an analog of SL(1278). Disruption of papA2 and papA1 in M. tuberculosis confirmed their essential role in SL-1 biosynthesis and their order of action. Finally, the Delta papA2 and Delta papA1 mutants were screened for virulence defects in a mouse model of infection. The loss of SL-1 (and SL(1278)) did not appear to affect bacterial replication or trafficking, suggesting that the functions of SL-1 are specific to human infection.     

Metabolic syndrome: an evolving threat in the genesis of coronary artery disease

Cardiovascular disease is an escalating worldwide health problem. Effective tools to predict and prevent its development and progression are needed. Correctly diagnosing the metabolic syndrome, which identifies people at higher risk for developing diabetes mellitus and cardiovascular disease, may be valuable in guiding treatment and prevention of these major disorders. Several important definitions of the metabolic syndrome have been proposed. The authors discuss these definitions and how they vary in terms of their relationship to incident cardiovascular disease, type 2 diabetes mellitus, and surrogate markers of atherosclerosis. Establishing clarity on what is meant by the metabolic syndrome and agreement as to its underlying basis is needed to reach consensus between the many different definitions that have been proposed. This is particularly the case if it is to become a useful adjunct in clinical practice to identify those who may benefit from more intensive lifestyle interventions and more detailed short-term risk assessments.     

Comorbidities play a larger role in predicting health-related quality of life compared to having an ostomy

BACKGROUND: Previous research suggests an ostomy worsens health-related quality of life (HR-QOL), but comorbidities also can affect HR-QOL. METHODS: Eligible patients had abdominal operation with ostomy (cases) or similar procedure without ostomy (controls). Patients were recruited for this case-control study from 3 Veterans Affairs hospital medical and pharmacy records. Comorbidities were assessed with Charlson-Deyo Comorbidity Index. Multinomial logistic regression evaluated the impact of comorbidities and having an ostomy on HR-QOL, measured using the Medical Outcomes Study Short Form 36 for Veterans. RESULTS: A total of 237 ostomates (cases) and 268 controls were studied. Average age was 69 years; 64% of cases had colostomy, 36% ileostomy. Twenty-nine percent of patients had a high level of comorbidities. Cases and controls were similar except for reasons for undergoing surgery. High comorbidity was a significant predictor of low HR-QOL in 6 domains of the Short Form 36 for Veterans; having an ostomy was a significant predictor in 4. CONCLUSIONS: High comorbidity significantly influences low HR-QOL and impacted more domains than having an ostomy.     

Localized pericardial constriction resulting in a "dumbbell" heart

We describe an unusual case of a young man presenting with calcific constrictive pericarditis. The patient had a history of restrictive cardiomyopathy and pericardial effusion during infancy and received antituberculous treatment. Investigations revealed the presence of thickened pericardium and a thickened calcific constrictive band around the atrioventricular groove posteriorly and over the infundibulum anteriorly. Intraoperatively, the band caused the heart to have a "dumbbell" appearance. A pericardiectomy was performed along with excision of the constricting band. The patient had an uneventful recovery.     

Downregulation of Inflammatory Responses by Novel Caffeic Acid Ester Derivative by Inhibiting NF-kappa B

Introduction  Considering anti-tumorigenic activity of caffeic acid phenyl ester, synthesis of several esterified form of caffeic acid is a novel approach in designing for potent drugs. Results  Our study demonstrates that esterified caffeic acid with methyl vanillate, termed as caffeic acid methyl vanillate ester (CAMVE), blocked inflammatory stimuli-induced inflammatory responses. It decreased amounts of iNOS, Cox-2, and ICAM1 by inhibiting NF-κB through inhibition of IKK activity, IκBα degradation, and p65 nuclear translocation. Conclusion  Overall, our data suggest that novel caffeic acid ester down-regulates inflammatory responses through inhibition of NF-κB and dependent several gene expressions, further suggesting its efficacy as a promising therapeutic agent.