Daunorubicin induced Stevens‐Johnson syndrome: A case report

Clinicians should consider the possible association of Daunorubicin with Stevens‐Johnson syndrome (SJS), administer it with caution and promptly evaluate all subsequently developing cutaneous reactions with a high index of suspicion for Stevens‐Johnson syndrome.     

Live/Real Time Three‐Dimensional Transthoracic Echocardiographic Assessment of Pericardial Disease

We studied 19 patients with pericardial disease using two‐dimensional and three‐dimensional transthorathic echocardiography (2DTTE and 3DTTE, respectively) in order to determine whether 3DTTE provides incremental value on top of 2DTTE in the evaluation of these patients. With 3DTTE a more comprehensive assessment of pericardial effusion can be made and both the parietal and visceral layers of the pericardium can be visualized en face and examined for pathologies and fibrin deposits. In our series of patients, 3DTTE was superior to 2DTTE in uncovering mass lesions involving the pericardium such as tuberculous granulomas and metastatic disease. Furthermore, it provided a better assessment of the nature of pericardial lesions, such as pericardial and mediastinal hematomas, pericardial cysts, and metastatic disease to the pericardium by sequential cropping of the 3D data sets and visualizing the interior of the lesions in a manner not possible with 2DTTE. It was also valuable in determining the extent of pericardial calcification in pericardial constriction and in measuring the size of pericardial masses. These preliminary results suggest the superiority of 3DTTE over 2DTTE in the evaluation of pericardial diseases and that it provides incremental knowledge to the echocardiographer. (ECHOCARDIOGRAPHY, Volume 26, November 2009)     

Familial crossed polysyndactyly in four generations of an Indian family

Background  

Polydactyly is the most common malformation of the limbs. “Crossed” polydactyly of hands and feet, i.e., preaxial in one and postaxial in the other, is extremely rare. It has not been included in the standard classification of hand and feet anomalies.     

Optimal methods for the preservation of cartilage samples in MRI and correlative biochemical studies.

MRI studies of cartilage require the prevention of sample degradation before and during scanning and during shipment for correlative studies. Methods to achieve this include immersion in protease inhibitors (PIs), refrigeration, and freezing. In this study, bovine nasal cartilage (BNC) samples were stored in Dulbecco's phosphate-buffered saline (DPBS), DPBS with standard PIs, or PI solution with GM6001, a potent metalloproteinase inhibitor. For each buffer, three samples were scanned at +4 degrees C and stored at +4 degrees C or at -20 degrees C with thawing prior to imaging. T2 and magnetization transfer (MT) rate, km, were measured weekly over 4 months, after which time water and glycosaminoglycan (GAG) contents were compared with those of matching tissue excised pre-storage. Samples in DPBS exhibited increased T2 (+33.6% after 1 month at +4 degrees C, P = 0.040) and decreased km (-20.6%, P = 0.004), while refrigeration in DPBS with PI and GM6001 yielded good stability (T2: +2.7%, P = 0.874; km: -4.2%, P = 0.654 after 108 days at +4 degrees C). Water content increased while GAG content markedly decreased in all samples. Thus, stability in cartilage MRI parameters can be optimized with appropriate storage conditions, but storage time should nonetheless be minimized.     

Evaluation of high‐fat high‐fructose diet treatment in factor VIII (coagulation factor)‐deficient mouse model

Non‐alcoholic fatty liver disease (NAFLD)‐like conditions enhance the production and action of clotting factors in humans. However, studies examining the effect of NAFLD due to high‐fat high‐fructose (HFHF) diet in factor VIII‐deficient (haemophilia A) animals or patients have not been reported previously. In this study, we investigated the individual role of factor VIII in the progression of diet‐induced NAFLD in the factor 8^?/? (F8^?/?) mouse model system and its consequences on the haemophilic status of the mice. The F8^?/? mice were fed with HFHF diet for 14 weeks. Physiological, biochemical, haematological, molecular, pathological, and immune histochemical analyses were performed to evaluate the effect of this diet. The F8^?/? mice developed hepatic steatosis after 14 weeks HFHF diet and displayed lower energy metabolism, higher myeloid cell infiltration in the liver, decreased platelet count, upregulated de novo fatty acid synthesis, lipid accumulation, and collagen deposition. This study helps to understand the role of factor VIII in NAFLD pathogenesis and to analyse the severity and consequences of steatosis in haemophilic patients as compared to normal population. This study suggests that haemophilic animals (F8^?/? mice) are highly prone to hepatic steatosis and thrombocytopenia.     

Excitatory cholecystokinin neurons of the midbrain integrate diverse temporal responses and drive auditory thalamic subdomains

The central nucleus of the inferior colliculus (ICC) integrates information about different features of sound and then distributes this information to thalamocortical circuits. However, the lack of clear definitions of circuit elements in the ICC has limited our understanding of the nature of these circuit transformations. Here, we combine virus-based genetic access with electrophysiological and optogenetic approaches to identify a large family of excitatory, cholecystokinin-expressing thalamic projection neurons in the ICC of the Mongolian gerbil. We show that these neurons form a distinct cell type, displaying uniform morphology and intrinsic firing features, and provide powerful, spatially restricted excitation exclusively to the ventral auditory thalamus. In vivo, these neurons consistently exhibit V-shaped receptive field properties but strikingly diverse temporal responses to sound. Our results indicate that temporal response diversity is maintained within this population of otherwise uniform cells in the ICC and then relayed to cortex through spatially restricted thalamic subdomains.

Before reaching the central nucleus of the inferior colliculus (ICC), auditory information is divided into parallel pathways that extract discrete acoustic features, including loudness, spectral information, and localization cues. Parallel inputs recombine in the ICC, which sends information via the ascending tectothalamic pathway to the primary auditory thalamus (ventral division of the medial geniculate body, vMGB) en route to the cortex. Despite their critical position at the nexus between the brainstem and the forebrain, the role of tectothalamic ICC neurons in integrating input features remains controversial. The lemniscal tectothalamic input is commonly regarded as a single phenotype, failing to account for the anatomical and physiological diversity of ICC neurons. Furthermore, it is unclear if the functional diversity of the ICC is a reflection of input patterns or a reflection of intrinsic properties.Many ICC neurons exhibit responses in vivo that closely resemble inputs from brainstem nuclei carrying spatial information (1–4), suggesting that the ICC collects and reroutes previously processed signals. However, in vivo recordings from guinea pig ICC have shown a continuum in the shape of frequency receptive fields, not the discrete categories that would be expected if responses were merely inherited (5). Although the receptive fields of ICC neurons can resemble those of lower nuclei, intracellular recordings revealed that a complex interplay between inhibitory and excitatory inputs to ICC neurons can also create receptive fields de novo (6, 7). These observations suggest that the ICC does not simply reroute inherited information but instead plays a more transformative role.Morphologically, ICC neurons consist of either cells with disk-shaped dendritic arbors flattened along the plane of the isofrequency laminae, or stellate cells with dendrites running across isofrequency laminae (8–11). However, dendritic morphology appears to correlate little with membrane properties and firing patterns in vitro (12–16) or with in vivo receptive fields (15–17), and it has remained unclear how much intrinsic membrane properties interact with synaptic inputs to shape auditory information.Here we identify an ICC neuron population that forms the major lemniscal excitatory projection to the MGB. These cholecystokinin (CCK) expressing neurons exhibit homogeneous intrinsic firing patterns and synaptic properties in vitro and V-shaped frequency receptive fields in vivo. However, even within this seemingly uniform population, we observed diverse temporal responses to tones in vivo, likely reflecting complexity in both intrinsic and extrinsic connectivity. Our results are consistent with a view of midbrain processing where individual cell types perform diverse processing tasks but mediate the convergence of this information onto specific target areas.     

Multicenter Clinical Evaluation of the Novel Alere i Strep A Isothermal Nucleic Acid Amplification Test

Rapid detection of group A beta-hemolytic streptococcus (GAS) is used routinely to help diagnose and treat pharyngitis. However, available rapid antigen detection tests for GAS have relatively low sensitivity, and backup testing is recommended in children. Newer assays are more sensitive yet require excessive time for practical point-of-care use as well as laboratory personnel. The Alere i strep A test is an isothermal nucleic acid amplification test designed to offer highly sensitive results at the point of care within 8 min when performed by nonlaboratory personnel. The performance of the Alere i strep A test was evaluated in a multicenter prospective trial in a Clinical Laboratory Improvement Amendments (CLIA)-waived setting in comparison to bacterial culture in 481 children and adults. Compared to culture, the Aleri i strep A test had 96.0% sensitivity and 94.6% specificity. Discrepant results were adjudicated by PCR and found the Alere i strep A test to have 98.7% sensitivity and 98.5% specificity. Overall, the Alere i strep A test could provide a one-step, rapid, point-of-care testing method for GAS pharyngitis and obviate backup testing on negative results.     

Detection of Group A Streptococcus in Pharyngeal Swab Specimens by Use of the AmpliVue GAS Isothermal Helicase-Dependent Amplification Assay

We evaluated the clinical performance (sensitivity and specificity) of the AmpliVue group A Streptococcus (GAS) isothermal helicase-dependent amplification assay using 1,192 pharyngeal swab specimens. AmpliVue GAS assay results were compared to the results of routine throat cultures on selective streptococcal blood agar plates. The sensitivity and specificity of the AmpliVue GAS assay were 98.3% (95% confidence interval [CI], 95 to 100%) and 93.2% (95% CI, 91 to 95%), respectively.