A further critical evaluation of requests for electrodiagnostic examinations

Abstract The aim of this study was to evaluate the impact of electrophysiological (EDX) tests in the clinical management and diagnosis of patients, and the appropriateness of the referral diagnosis. A study was carried out in three electrodiagnostic services in the Torino area, over a 12-month period. In our study 3,900 individuals (2,340 females, 1,560 males) were evaluated. Patients underwent EDX examinations including nerve conduction study, electromyography and repetitive stimulation test. Most patients had been sent for EDX tests by specialists. Specialists suspected mainly polyneuropathy, whilst general practitioners suspected mainly carpal tunnel syndrome. Seventy-two percent of the requests were correctly formulated, 55% by general practitioners and 77% by specialists. There was a concordance between the results of the EDX tests and diagnostic hypothesis 40% of the time. This study confirms the usefulness and diagnostic impact of EDX examinations and evidences the amount of time and resources wasted as a result of incorrect or incomplete requests.     

Phenothiazines induce PP2A-mediated apoptosis in T cell acute lymphoblastic leukemia

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer that is frequently associated with activating mutations in NOTCH1 and dysregulation of MYC. Here, we performed 2 complementary screens to identify FDA-approved drugs and drug-like small molecules with activity against T-ALL. We developed a zebrafish system to screen small molecules for toxic activity toward MYC-overexpressing thymocytes and used a human T-ALL cell line to screen for small molecules that synergize with Notch inhibitors. We identified the antipsychotic drug perphenazine in both screens due to its ability to induce apoptosis in fish, mouse, and human T-ALL cells. Using ligand-affinity chromatography coupled with mass spectrometry, we identified protein phosphatase 2A (PP2A) as a perphenazine target. T-ALL cell lines treated with perphenazine exhibited rapid dephosphorylation of multiple PP2A substrates and subsequent apoptosis. Moreover, shRNA knockdown of specific PP2A subunits attenuated perphenazine activity, indicating that PP2A mediates the drug’s antileukemic activity. Finally, human T-ALLs treated with perphenazine exhibited suppressed cell growth and dephosphorylation of PP2A targets in vitro and in vivo. Our findings provide a mechanistic explanation for the recurring identification of phenothiazines as a class of drugs with anticancer effects. Furthermore, these data suggest that pharmacologic PP2A activation in T-ALL and other cancers driven by hyperphosphorylated PP2A substrates has therapeutic potential.     

High prevalence of neuropathies in patients with end‐stage liver disease

Cocito D, Maule S, Paolasso I, Castelli L, Ciaramitaro P, Poglio F, Ottobrelli A, Grimaldi S. High prevalence of neuropathies in patients with end‐stage liver disease.
Acta Neurol Scand: 2010: 122: 36–40.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – Peripheral neuropathy has been reported in association with end‐stage liver disease, but there is only a limited number of reports on the incidence and features of these neuropathies. Materials and methods – In this study, 83 patients awaiting liver transplantation were evaluated for the presence of peripheral and autonomic neuropathy. Results – Sixty‐five percent of the patients had evidence of neuropathy, in agreement with peripheral NCS or cardiovascular autonomic function test. The neuropathy was more frequent in patients with advanced hepatic failure, evaluated with the MELD score. The most frequent abnormalities in nerve conduction studies were sensory‐motor neuropathies and sensory neuropathies, with a length‐dependent pattern. Conclusion – Peripheral neuropathy and autonomic neuropathy are common in patients with end‐stage liver disease with different etiology and correlate with the severity of the liver disease.     

Differential diagnosis of chronic dysimmune demyelinating polyneuropathies with and without anti-MAG antibodies

The distinction between chronic demyelinating polyneuropathies associated with IgM paraproteinemia and anti-myelin-associated glycoprotein (MAG) antibodies (MAG-PN) and chronic inflammatory demyelinating polyneuropathies (CIDPs) relies on the anti-MAG antibodies assay. The aim of the study was to identify clinical and electrophysiological features suggesting a diagnosis of MAG-PN. Fourteen patients with MAG-PN and 35 with CIDP were included, and a discriminant analysis was performed to identify the clinical and electrophysiological features suggestive of MAG-PN. Pure sensory clinical phenotype, low median and ulnar terminal latency index, and absence of M responses in the lower limbs were significantly associated with the diagnosis of MAG-PN, and indicate a moderate to large increase in probability of this diagnosis in patients with chronic dysimmune demyelinating polyneuropathies.     

Pain affects the quality of life of neuropathic patients

Abstract The aim of this study was to verify the extent to which the presence of pain affects the quality of life (QoL) of neuropathic patients. The patients were selected in our Department of Peripheral Nervous System Diseases. We enrolled 120 consecutive patients with chronic polyneuropathy who had not received continuous pain therapy during the two months preceding study entry, and administered them the Total Neuropathy Score (TNS), the official Italian version of the SF-36 and the Italian Pain Questionnaire (QUID). Our main finding was that the QoL is affected not only by the presence of neuropathy, but also by the presence and intensity of pain: the physical aspect of the QoL correlated only weakly with the TNS, but pain was closely related to a worsening in this parameter; moreover, the mental domains of the SF-36 were only correlated with pain. Pain per se worsens the QoL of neuropathic patients, regardless of disease severity.     

Simultaneous palatal pleomorphic adenoma and mandibular keratocystic odontogenic tumor in a pediatric patient

BACKGROUND: Neoplasms of the salivary gland account for 3% of all head and neck tumors; most of these occur in the parotid gland and are benign; 80% of them are pleomorphic adenomas. Benign neoplasms of the salivary gland are rare in children compared with adults. Keratocystic odontogenic tumor (KCOT) is considered the second most frequent neoplasm of all odontogenic tumors after the ameloblastoma. In the present report, we introduce the unusual presentation of a child with a simultaneous pleomorphic adenoma of the right hard palate and a KCOT of the left mandibular angle. DISCUSSION: The case is significant for 2 reasons; according to the literature, there are few reports of pleomorphic adenoma arising from a minor salivary gland of the palate in a patient younger than 18 years. This is to our knowledge the first recorded instance of simultaneous palatal pleomorphic adenoma and mandibular KCOT occurring in a child.     

Subclinical electrophysiological alterations of phrenic nerve in chronic inflammatory demyelinating polyneuropathy

Alterations of the phrenic nerve (PN) and pulmonary function tests (PFTs) have been described in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). This study was aimed at assessing the relationship between PN and respiratory function in CIDP patients without clinical signs of respiratory failure. Bilateral PN and right median nerve conduction studies were carried out along with blood gas analysis and PFTs: maximal inspiratory pressure; maximal expiratory pressure; forced vital capacity. The amplitude of the compound muscle action potential of the PN was seen to be altered in 19/24 (79%) patients and latency in 22 (92%). Eighteen patients (75%) showed at least one abnormal PFTs or CO₂ partial pressure value. Electrophysiological alterations of the PN were observed in a high percentage of the CIDP patients studied. No statistically significant correlation was observed between PN and PFTs alterations.     

Population data for 15 autosomal STRs loci and 12 Y chromosome STRs loci in a population sample from the Sardinia island (Italy)

One hundred twenty-five unrelated individuals (69 females and 56 males) from Sassari (Northern Sardinia) and Orgosolo (Central Sardinia) were typed for 15 STRs loci. The 56 males were typed for 12 Y chromosome STRs loci too. Frequency distribution is described.