Acute flaccid paralysis due to West nile virus infection in adults: A paradigm shift entity

Three cases of acute flaccid paralysis (AFP) with preceding fever are described. One patient had a quadriparesis with a florid meningoencephalitic picture and the other two had asymmetric flaccid paralysis with fasciculations at the onset of illness. Magnetic resonance imaging in two cases showed prominent hyperintensitities in the spinal cord and brainstem with prominent involvement of the grey horn (polio-myelitis). Cerebrospinal fluid (CSF) polymerase chain reaction was positive for West Nile virus (WNV) in the index patient. All three cases had a positive WNV immunoglobulin M antibody in serum/CSF and significantly high titer of WNV neutralizing antibody in serum, clearly distinguishing the infection from other Flaviviridae such as Japanese encephalitis. WNV has been recognized in India for many decades; however, AFP has not been adequately described. WNV is a flavivirus that is spread by Culex mosquitoes while they take blood meals from humans and lineage 1 is capable of causing a devastating neuro-invasive disease with fatal consequences or severe morbidity. We describe the first three laboratory confirmed cases of WNV induced AFP from Kerala and briefly enumerate the salient features of this emerging threat.     

Evaluation of capsular and acapsular strains of S. aureus in an experimental brain abscess model

Brain abscesses are mainly caused by either direct or indirect inoculation of gram positive bacteria including Stapylococcus aureus (S. aureus) or Streptococcus species into the central nervous system. In the present study, we aimed to compare potential changes in brain abscess pathogenesis induced by two different strains of S. aureus, namely the laboratory strain RN6390 and the clinical isolate Reynolds. Although the Reynolds strain was expected to be more resistant to eradication by the host, due to the existence of a polysaccharide capsule, and subsequently to be more virulent, instead we found parenchymal damage and mortality rates to be more prominent following RN6390 infection. In contrast, the Reynolds strain proliferated faster and induced early expression of the chemokine CXCL2, matrix metalloproteinase-9 (MMP-9), and complement 3a and C5. Furthermore, there were early and more abundant infiltration of PMNs, T cells and erythrocyte extravasation in brain abscesses induced by the Reynolds strain. However, several immune parameters were not different between the two strains during the later stages of the disease. These results suggest that capsular S. aureus can modulate innate immunity and complement system activation differently than the acapsular strain RN6390, and the early changes induced by Reynolds strain may have an important impact on survival.     

Auditory steady-state responses in normal hearing adults: a test-retest reliability study

The test-retest reliability of the auditory steady-state response (ASSR) has received limited attention. Therefore, the aim was to assess the test-retest reliability of an 80-Hz multiple-ASSR system in normal-hearing subjects by a comprehensive set of statistical methods. Twenty-nine participants (15 females) aged between 18 and 30 years contributed to two sessions (test-retest), and the ASSR thresholds were determined with a descending search protocol using a 10-dB precision. The test-retest reliability was assessed by a three-layered approach which consisted of Pearson product-moment correlation, analysis of variance (ANOVA), and standard error of measurement (SEM). The correlations for ASSR thresholds ranged from poor (0.34) for 500 Hz CF to moderate (0.55) for 1000, 2000, and 4000 Hz CF. A two-way ANOVA of the difference scores (ASSR threshold minus behavioral threshold) demonstrated no significant difference between test and retest. The SEM determined the normal tolerance for clinical error of repeated thresholds and the ASSR SEM values fell well within +/-10 dB HL. This investigation shows that the multiple ASSR-technique produces a clinically acceptable test-retest reliability for normal-hearing adults.     

Genome-wide copy number imbalances identified in familial and sporadic medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) is a malignant tumor of the calcitonin-secreting parafollicular C cells of the thyroid occurring sporadically and as a component of the multiple endocrine neoplasia type 2/familial medullary thyroid carcinoma syndrome. The primary genetic cause of multiple endocrine neoplasia type 2 is germline mutation of the RET protooncogene. Somatic point mutations in RET also occur in sporadic MTC. Although RET mutation is likely sufficient to cause C-cell hyperplasia, the precursor lesion to MTC, tumor progression is thought to be due to clonal expansion caused by the accumulation of somatic events. Using the genome-scanning technique comparative genomic hybridization, we identified chromosomal imbalances that occur in MTC including deletions of chromosomes 1p, 3q26.3-q27, 4, 9q13-q22, 13q, and 22q and amplifications of chromosome 19. These regions house known tumor suppressor genes as well as genes encoding subunits of the multicomponent complex of glycosylphosphatidylinositol-linked proteins (glial cell line-derived neurotrophic factor family receptors alpha-2-4) and their ligands glial cell line-derived neurotrophic factor, neurturin, persephin, and artemin that facilitate RET dimerization and downstream signaling. Chromosomal imbalances in the MTC cell line TT were largely identical to those identified in primary MTC tumors, consolidating its use as a model for studying MTC.     

Bone marrow engraftment analysis after granulocyte transfusion

We present the case of a 6-year-old male who received an allogeneic bone marrow transplant as part of treatment for acute lymphoblastic leukemia. The patient relapsed 5 months after transplantation and received additional chemotherapy. He acquired an angioinvasive fungal infection that required transfusion of granulocytes. Approximately 5 weeks after relapsing (181 days after transplant), a bone marrow specimen was taken for molecular engraftment analysis and flow cytometry to assess graft loss as well as residual disease. The engraftment results generated by the multiple short tandem repeat loci tested were inconsistent, and alleles were present at several loci that were of neither patient nor donor origin. An error in specimen identification was initially considered. Further investigation into the circumstances surrounding procurement of the patient's bone marrow aspirate revealed that the patient had received a granulocyte transfusion approximately 10 hours before the bone marrow specimen was taken. In addition, morphological and flow cytometric analyses of the same bone marrow aspirate demonstrated a significant degree of peripheral blood contamination. We determined that the unknown alleles in the bone marrow engraftment specimen were derived from the donor of the transfused granulocytes. This case illustrates that white cell transfusion can lead to erroneous bone marrow engraftment results, particularly if only one microsatellite locus is used to monitor engraftment.     

Cholestyramine—a useful adjunct for the treatment of patients with fecal incontinence

Aim/Background Cholestyramine may improve fecal incontinence, but its use has not been assessed. We report our experience with the use of cholestyramine in the treatment of fecal incontinence. Materials and methods Twenty-one patients (19 female, mean age 65 years) with fecal incontinence (≥1 episode/week) received cholestyramine along with biofeedback therapy (group A). Stool frequency, stool consistency (Bristol scale), number of incontinent episodes, satisfaction with bowel function (VAS), and anorectal physiology were assessed at 3 months and at 1 year after treatment. Data were compared with a matched group of 21 incontinent subjects (19 female, mean age 64 years) who received biofeedback alone (group B). Results At 3 months and at 1 year, group A patients showed decreased stool frequency (p < 0.01), stool consistency (p = 0.001), and number of incontinent episodes (p < 0.04). In contrast, stool frequency (p = 0.8) and stool consistency (0.23) were not different from baseline in group B subjects. In both groups, there was improvement in the satisfaction with bowel function (p < 0.05), anal sphincter pressures (p < 0.05) and ability to retain saline infusion (p < 0.05). Mean dose of cholestyramine used was 3.6 g; 13 subjects (62%) required dose titration, and 7 (33%) subjects reported minor side effects. Conclusion Cholestyramine is safe and useful adjunct for the treatment of diarrhea and fecal incontinence. Most patients require small doses, and dose titration is important. The improvement in stool characteristics favors a drug effect, over and above the benefits of biofeedback therapy. Portions of this work were presented at the 2006 American College of Gastroenterology Meeting, Las Vegas, Nevada and published as an abstract in Am J Gastroenterol 2006; 101 (Suppl):S210–S211.     

ESCRT factors restrict mycobacterial growth

Nearly 1.7 billion people are infected with Mycobacterium tuberculosis. Its ability to survive intracellularly is thought to be central to its success as a pathogen, but how it does this is poorly understood. Using a Drosophila model of infection, we identify three host cell activities, Rab7, CG8743, and the ESCRT machinery, that modulate the mycobacterial phagosome. In the absence of these factors the cell no longer restricts growth of the non-pathogen Mycobacterium smegmatis. Hence, we identify factors that represent unique vulnerabilities of the host cell, because manipulation of any one of them alone is sufficient to allow a nonpathogenic mycobacterial species to proliferate. Furthermore, we demonstrate that, in mammalian cells, the ESCRT machinery plays a conserved role in restricting bacterial growth.     

Prognosis following first-time myocardial infarction in patients with psoriasis: a Danish nationwide cohort study

Abstract. Ahlehoff O, Gislason GH, Lindhardsen J, Olesen JB, Charlot M, Skov L, Torp‐Pedersen C, Hansen PR. (Copenhagen University Hospital Gentofte, Hellerup; Copenhagen University Hospital Roskilde, Roskilde, Denmark). Prognosis following first‐time myocardial infarction in patients with psoriasis: a Danish nationwide cohort study. J Intern Med 2011; 270 : 237–244. Objectives. The magnitude of cardiovascular risk associated with psoriasis has been debated and the prognostic impact of psoriasis following myocardial infarction (MI) is unknown. Therefore, we investigated the risk of mortality and adverse cardiovascular events in patients with psoriasis following first‐time MI. Design, setting and participants. Cohort study of the entire Danish population including all individuals who experienced first‐time MI during the period 2002–2006. Multivariable Cox regression models were used to assess the post‐MI prognostic impact of psoriasis. Main outcome measures. All‐cause mortality and a composite cardiovascular end‐point of recurrent MI, stroke and cardiovascular death. Results. A total of 462 patients with psoriasis and 48 935 controls (mean age 69.5 and 70.6 years, respectively) were identified with first‐time MI during the study period. The mean follow‐up was 19.5 months [standard deviation (SD) 16.5] for patients with psoriasis and 22 .0 months (SD 18.7) for those without psoriasis. Incidence rates (IRs) per 1000 patient‐years for all‐cause mortality were 119.4 [95% confidence interval (CI) 117.2–138.3] and 138.3 (95% CI 114.1–167.7) for patients without and with psoriasis, respectively, and the adjusted hazard ratio (HR) associated with psoriasis was 1.18 (95% CI 0.97–1.43). For the composite end‐point, the IRs were 149.7 (95% CI 147.1–152.4) and 185.6 (95% CI 155.8–221.0) for patients without and with psoriasis, respectively, with an HR of 1.26 (95% CI 1.04–1.54) for patients with psoriasis. Conclusion. This first study of the impact of psoriasis on prognosis after first‐time MI indicated a significantly impaired prognosis in patients with psoriasis. Further studies of this novel association are warranted.     

Immunological diseases of the pancreatico-hepatobiliary system: update on etiopathogenesis and cross-sectional imaging findings

Immunological diseases of the hepatobiliary system and the pancreas include a broad spectrum of disorders that manifest characteristic histopathology/serology and variable clinical features and imaging findings. Recent studies have thrown fresh light on the complex role of genetics and autoimmunity in the pathogenesis and natural history of these diverse disorders that include autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, IgG4-related cholangitis, overlap/outlier syndromes, and autoimmune pancreatitis.