Closure of Large Patent Ductus Arteriosus in Renal Failure under Echocardiographic Guidance without Use of Radiographic Contrast Media

Large patent ductus arteriosus with large left‐to‐right shunt results in heart failure, and if untreated, leads to multiorgan dysfunction. Use of radiographic iodinated contrast media for angiogram during transcatheter duct closure may aggravate preexistent renal dysfunction. Aortogram with contrast media was avoided in a patient with renal failure, and echocardiogram guided deployment of duct occluder device in the cardiac catheterization laboratory for closure of a large duct. This article highlights use of a nitinol‐based occluder that employs nonporous polytetrafluoroethylene fabric to aid in instantaneous duct closure.     

Sex-specific control of flurothyl-induced tonic-clonic seizures by the substantia nigra pars reticulata during development

The substantia nigra pars reticulata (SNR) plays an important age- and sex-specific role in control of clonic seizures. Its involvement in control of tonic-clonic seizures is contradictory. We investigated the role of the SNR in the tonic-clonic seizures induced in male, female and neonatally castrated male rats using flurothyl. In adult female rats, vaginal impedance determined the changes in progesterone/estrogen ratio. Rats at various postnatal ages received infusions of muscimol or vehicle in the SNRanterior or SNRposterior. Furthermore, in 15-day-old (P15) and adult male rats, ZAPA (a GABA(A) receptor agonist) or AP7 (an NMDA receptor antagonist) was infused. The developmental profile of tonic-clonic seizure threshold differed between male and female rats possibly due to early postnatal testosterone surge in male rats. On the other hand, changing estrogen/progesterone ratio in cycling adult female rats had no effect on seizure threshold. Intranigral muscimol had proconvulsant effects on tonic-clonic seizures only in immature rats, and this effect was dependent on the perinatal testosterone surge. ZAPA had anticonvulsant effects in P15 rats but was not effective in adult rats. Only AP7 had anticonvulsant effects in both adult and P15 rats. Results indicate that thresholds for flurothyl-induced tonic-clonic seizures develop under the control of postnatal testosterone. Although GABAergic inhibition in the SNR affects tonic-clonic seizures in developing rats, only the NMDA antagonist had consistent anticonvulsant effects throughout development.     

Catheter closure of atrial septal defects with deficient inferior vena cava rim under transesophageal echo guidance

Objectives: To describe the case selection, imaging considerations, technique, and results of catheter closure of atrial septal defects (ASD) with deficient inferior vena cava (IVC) rim. Background: Transcatheter closure with Amplatzer septal occluder (ASO) has become standard treatment for most secundum ASDs. Defects with deficient IVC rim continue to be challenging to image and close in the catheterization laboratory. Methods: Records of 12 patients with deficient IVC rim (<5 mm), who underwent catheter closure (April 2007 to June 2008) were reviewed. General anesthesia and transesophageal echo (TEE) guidance was used in all. The IVC rim was imaged at 70°–90° with retroflexion of the TEE probe, in addition to the conventional views. Devices 1–4 mm > maximal ASD size were selected. Deployment was accomplished either from the left atrium, left upper or from the right pulmonary veins. Results: The median age was 5.5 (2.5–27) years and median weight was 19.5 (9‐65) kg. The defects measured 16–32 mm and 18–36 mm septal occluders were used. The median fluoroscopic time was 13.1 (4.2–32.7) min. Initial device selection was revised in four patients. Two patients had residual flows at IVC margin. The device embolized to right ventricular outflow tract in one patient. This was retrieved, and a larger device was deployed. No other complications were observed immediately or on follow‐up (median 6; range 1–14 months). Conclusions: Transcatheter closure of ASDs with deficient IVC rim is feasible under TEE guidance. The modified retroflexed view allows adequate imaging of IVC rim through TEE. © 2008 Wiley‐Liss, Inc.     

A short overview on the role of alpha-synuclein and proteasome in experimental models of Parkinson's disease

The Ubiquitin Proteasome System is a multi-enzymatic pathway which degrades polyubiquinated soluble cytoplasmic proteins. This biochemical machinery is impaired both in sporadic and inherited forms of Parkinsonism. In the present paper we focus on the role of the pre-synaptic protein alpha-synuclein in altering the proteasom based on the results emerging from experimental models showing a mechanistic chain of events between altered alpha-synuclein, proteasome impairment and formation of neuronal inclusions and catecholamine cell death.     

Gene expression and protein localization of calmodulin-dependent phosphodiesterase in adult rat retina

Calcium calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) was identified in crude extract and immunolabeled sections of rat retina. Both cAMP and cGMP PDE activities were stimulated by calcium-calmodulin (4.7-fold and 2.3-fold, respectively). To characterize PDE1 isoforms in retinal cells further, we used antibodies that specifically recognize PDE1 gene products. PDE1B antibody stained a band at molecular mass of 63 kDa whereas PDE1C antibody recognized two bands at 74- and 70-kDa molecular masses. Two PDE1A antibodies (against N-terminal and C-terminal peptides) detected a band at 79 kDa never described before. Immunohistochemical analysis showed a distribution of PDE1A in the outer retina with a bright fluorescence in the outer segments of photoreceptors. PDE1B is uniformly distributed across the retina. PDE1C is confined mainly to the inner retina, with a precise localization in the inner nuclear layer. Immunostaining with choline acetyltransferase antibody indicates localization in cholinergic amacrine cell. The present data provide evidence of expression of PDE1 isoforms in mammalian retina with a complementary distribution of PDE1A and PDE1C, suggesting different roles in retinal function.     

A hypothesis on prion disorders: are infectious, inherited, and sporadic causes so distinct?

Prion diseases include a group of either sporadic, inherited or infectious disorders characterized by spongiform neurodegeneration and reactive glyosis in several brain regions. Whatever the origin, the neuropathological hallmark of prion diseases is the presence of brain aggregates containing an altered isoform of a cellular protein, named prion protein. Recent findings show the potential toxicity of the normal cellular prion protein, which occurs when its physiological metabolism is altered. In particular, several studies demonstrate that accumulation of the prion protein in the cytosol can be a consequence of an increased amount of misfolded prion proteins, a derangement of the correct protein trafficking or a reduced activity of the ubiquitin-proteasome system. The same effects can be a consequence of a mutation in the gene coding for the prion protein. In all these conditions, one assists to accumulation and self-replication of insoluble prion proteins which leads to a severe disease resembling what observed following typical "prion infections". This article provides an opinion aimed at reconciling the classic Prusiner's theory concerning the "prion concepts" with the present knowledge arising from experimental studies on neurodegenerative disorders, suggesting a few overlapping steps in the pathogenesis of these diseases.     

Do MRI features distinguish Wilson's disease from other early onset extrapyramidal disorders? An analysis of 100 cases

Magnetic resonance imaging (MRI) is frequently used in the evaluation of various extrapyramidal disorders. Among the plethora of MRI features in Wilson's disease (WD), only “face of the giant panda” sign has been recognized to distinguish WD from other early onset extrapyramidal disorders (EOEPD). To ascertain the value of various MRI features in differentiating neuropsychiatric form of WD from other EOEPD. This retrospective analysis included 100 patients (M:F = 56:44) of EOEPD (5–40 years), who had undergone MRI during Jan'03 to Nov'08. Their clinical features were recorded and the following MR sequences were analyzed: T1WI, T2WI, FLAIR. Fifty‐six patients had WD (M:F = 28:30, age at onset: 14 ± 6.8 years) and 44 had other EOEPD (M:F = 27:17, age at onset: 19 ± 9.8 years) that included Huntington's disease‐4, young‐onset Parkinson's disease‐7, mitochondrial disorders‐2, Hallervorden‐Spatz disease‐8, non‐Wilsonian hepatolenticular degeneration‐2, toxic/metabolic disorder‐1, and others‐20. The duration of illness at the time of MRI was comparable (WD: 3.1 ± 4.9 years; Other EOEPD: 2.8 ± 2.4 years). MR signal characteristics varied in topography and severity in both the groups. All the patients of WD had signal abnormalities in MRI, as against 16/44 of the other EOEPD group. The following MR observations were noted exclusively in WD: “Face of giant panda” sign (14.3%), tectal plate hyperintensity (75%), central pontine myelinolysis (CPM)‐like abnormalities (62.5%), and concurrent signal changes in basal ganglia, thalamus, and brainstem (55.3%). Besides “Face of giant panda” sign, hyperintensities in tectal‐plate and central pons (CPM‐like), and simultaneous involvement of basal ganglia, thalamus, and brainstem are virtually pathognomonic of WD. © 2010 Movement Disorder Society     

Amputation and the assessment of limb viability: perceptions of two hundred and thirty two orthopaedic trainees

INTRODUCTION

The management of complex extremity injury, which may require assessment of limb viability and performance of amputation, is a challenge to those involved in its emergent and definitive care. Concern exists regarding the exposure of orthopaedic trainees to such cases due both to changes in training and centralisation of trauma services.

SUBJECTS AND METHODS

This is a web-based observational study by survey, investigating the confidence and perceived adequacy of training of UK orthopaedic specialist trainees in the assessment of limb viability and amputation surgery. 222 responses from 888 trainees were required to achieve a < 5% error rate with 90% confidence; 232 surveys were completed.

RESULTS

Trainee confidence in dealing with the assessment of limb viability is high despite infrequent exposure to cases. The majority of trainees perceive their training in limb viability assessment as adequate. For performance of amputation, exposure is minimal, confidence is lower and 36% of trainees regard their training as inadequate.

CONCLUSIONS

Limb viability assessment is an area in which trainees feel confident and well trained. There is, however, a perceived training inadequacy in amputation surgery and a corresponding lack of confidence for many trainees, irrespective of training year. This is the first study to offer an insight into specific training experiences of junior orthopaedic surgeons at a national level and it should drive the development of opportunities for trainees to develop skills in amputation surgery.