hERG1 channels drive tumour malignancy and may serve as prognostic factor in pancreatic ductal adenocarcinoma.

BACKGROUND: hERG1 channels are aberrantly expressed in human cancers. The expression, functional role and clinical significance of hERG1 channels in pancreatic ductal adenocarcinoma (PDAC) is lacking. METHODS: hERG1 expression was tested in PDAC primary samples assembled as tissue microarray by immunohistochemistry using an anti-hERG1 monoclonal antibody (α-hERG1-MoAb). The functional role of hERG1 was studied in PDAC cell lines and primary cultures. ERG1 expression during PDAC progression was studied in Pdx-1-Cre,LSL-Kras(G12D/+),LSL-Trp53(R175H/+) transgenic (KPC) mice. ERG1 expression in vivo was determined by optical imaging using Alexa-680-labelled α-hERG1-MoAb. RESULTS: (i) hERG1 was expressed at high levels in 59% of primary PDAC; (ii) hERG1 blockade decreased PDAC cell growth and migration; (iii) hERG1 was physically and functionally linked to the Epidermal Growth Factor-Receptor pathway; (iv) in transgenic mice, ERG1 was expressed in PanIN lesions, reaching high expression levels in PDAC; (v) PDAC patients whose primary tumour showed high hERG1 expression had a worse prognosis; (vi) the α-hERG1-MoAb could detect PDAC in vivo. CONCLUSIONS: hERG1 regulates PDAC malignancy and its expression, once validated in a larger cohort also comprising of late-stage, non-surgically resected cases, may be exploited for diagnostic and prognostic purposes in PDAC either ex vivo or in vivo.

The increase of endothelial progenitor cells in the peripheral blood: a new parameter for detecting onset and severity of sepsis.

Sepsis is a clinical syndrome characterized by non-specific inflammatory response with evidence of profound changes in the function and structure of endothelium. Recent evidence suggests that vascular maintenance, repair and angiogenesis are in part mediated by recruitment from bone marrow (BM) of endothelial progenitor cells (EPCs). In this study we were interested in whether EPCs are increasingly mobilized during sepsis and if this mobilization is associated with sepsis severity. Our flow cytometry data demonstrate that in the CD34+ cell gate the number of EPCs in the blood of patients with sepsis had a four-fold increase (45 +/- 4.5% p < 0.001) compared to healthy controls (12 +/- 3.6%) and that this increase was already evident at 6 hours from diagnosis (40.6 +/- 4.2 percent), reaching its maximum at 72 hours. Also the percentage of cEPCs identified in the patients with sepsis (35 +/- 4.6% of the CD34+ cell) was statistically different (p < 0.001) compared to that found in the blood of patients with severe sepsis (75 +/- 4.9%). In addition, we proved that at six hours after sepsis diagnosis, VEGF, CXCL8 and CXCL12 serum levels were significantly higher in septic patients compared to healthy volunteers 559 +/- 82.14 pg/ml vs 2.9 +/- 0.6 (p < 0.0001), 189.8 +/- 67.3 pg/ml 15 vs 11.9 +/- 1.6 (p = 0.014) and 780.5 +/- 106.5 pg/ml; vs 190.2 +/- 71.4 (p < 0.001). Our data suggest that the cEPC evaluation in peripheral blood, even at early times of diagnosis, in patients with sepsis can be envisaged as a valuable parameter to confirm diagnosis and suggest further prognosis.

Campos eletromagneticos produzidos por equipamentos de ondas curtas usados em fisioterapia: uma avaliaçäo em Presidente Prudente, SP

Este trabalho tem o objetivo de avaliar a quantidade de radiacao eletromagnetica a que o fisioterapeuta esta submetido quando utiliza equipamentos de ondas curtas no tratamento de pacientes, em clinicas de Fisioterapia de Presidente Prudente, SP. Para isso, foram medidas densidades de potencia em alguns lugarres proximo ao paciente e ao equipamento, durante um procedimento-padrao de tratamento de coluna lombar. O paciente foi colocado em decubito dorsal e foram usados eletrodos (ou aplicadores) de placas. Os locais escolhidos para medidas foram: 1) acima do painel do equipamento, 2) ao redor do cabo dos aplicadores e 3) na altura do abdomem e dos olhos do paciente. As medidaas foram feitas usando um medidor de densidade de potencia (mW/cm) NARDA, com um sensor para a faixa de frequencia de 10 a 300 Mhz. Os resultados mostram uma queda exponencial da intensidade, em funcao da distancia ao ponto escolhido. Alguns equipamentos apresentam valores da densidade de potencia de ate 20mWcm, proximo dos cabos e dos aplicadores. Acima do painel de controle do equipamento os valores variam de 0,5 a 4,0 mW/cm em distancias de ate 30 cm. Proximo aos olhos do paciente o valor medido e da ordem de 2,0 mW/cm. Esses resultados indicam que em alguns locais o fisioterapeuta esta sujeito a riscos de exposicao acima dos valores recomendados pelos orgaos internacionais

Decreased EMG median frequency during a second bout of eccentric contractions.

PURPOSE: Others have reported preferential recruitment of fast motor units in muscles during performance of eccentric contractions and there is evidence that fast muscle fibers are more susceptible to eccentric contraction-induced injury. We tested the hypothesis that during a second bout of maximal eccentric contractions 1 wk after the first, there would be a reduction in the electromyographic (EMG) median frequency (MF) with minimal change in the EMG root-mean-square (RMS), indicating greater reliance on slower motor units. This could provide an explanation for the enhanced resistance to eccentric contraction-induced injury after a single bout of eccentric exercise. METHODS: Human subjects performed 50 maximal voluntary eccentric (N = 10) or concentric (N = 10) contractions of the anterior crural muscles on two occasions separated by 1 wk. To determine whether MF changes during the second bout could be a consequence of injury to fibers in fast motor units, the anterior crural muscles of mice were electrically stimulated to perform 50 maximal eccentric (N = 10) or concentric (N = 9) contractions on two occasions separated by 1 wk. In both the humans and mice, torque production and tibialis anterior muscle RMS and MF were measured during the two exercise bouts. RESULTS: In human tibialis anterior muscle, MF was 30% lower (P < 0.01) during the second eccentric bout although RMS was the same. In the mice, RMS and MF were unchanged at any time after the first eccentric bout despite torque deficits similar to those observed in the humans. CONCLUSIONS: The data indicate that with repetition of maximal voluntary eccentric contractions, there is an increased activation of slow motor units and a concomitant decrease in activation of fast units.

Electromyographic study of the longissimus dorsi and iliocostalis lumborum muscles during knee flexion and extension on a plain and on a tilt Roman table.

The objective of this paper was to analyse the activity of the longissimus dorsi and the iliocostalis lumborum muscles--components of the erector spinae muscle--in order to determine: their action potentials during the use of a plain and a tilt Roman table; 2) to compare the action potentials of the two muscles; 3) to verify if the action potential of these two muscles remain constant during the arc of movement--knee flexion and extension--divided into angle ranges, and 4) to compare the action potentials of the muscles in movements performed in a free manner and against resistance. Twenty-three young volunteers were studied electromyographically and each muscle received a needle electrode (Mise) and a surface electrode. The results showed that the table model did not determine any difference in the action potential of the muscles and that, on average, the iliocostalis lumborum muscle developed a slightly higher action potential than the longissimus dorsi muscle during the free flexion of knees on the plain table. In more than 70% of the cases, there was no difference between the action potential of the muscles over the various angle ranges of knee flexion and extension. Relatively higher action potentials were recorded during knee flexion and extension against resistance than during the same movements performed in a free manner. This shows that the paravertebral musculature responds better to an overload (8 kg) imposed on the knee flexor group, confirming the stabilizing role of the longissimus dorsi and iliocostalis lumborum muscles during knee flexion and extension on a Roman table.

Clinical magnetocardiography. 10 years experience at the Catholic University.

Since the introduction, in 1982, of a Biomagnetic facility in the clinical environment, efforts were concentrated to investigate whether magnetocardiography could really provide new information of potential diagnostic use, even avoiding electromagnetic shielding to facilitate simultaneous biomagnetic and conventional cardiac investigations, including cardiac catheterization for invasive electrophysiological procedures. More than 350 patients have been magnetically investigated using a single-channel second-order gradiometer. Results of 281 MCG studies, whose data have been extensively analyzed with updated software programs, are reported. Magnetocardiographic (MCG) mapping during endocardial pacing was performed to quantify the accuracy of MCG localization of intracardiac dipolar sources. MCG classification of ventricular preexcitation has been attempted in 70 patients with overt preexcitation. MCG localization of the ventricular preexcited area was accurate and reproducible, provided that during mapping a sufficient degree of ventricular preexcitation was present. MCG mapping during orthodromic A-V re-entry tachycardia has been also employed to attempt the localization of retrograde atrial preexcitation as well as the site of origin of atrial and ventricular tachyarrhythmias. For validation, the results of catheter and epicardial mappings have been used. Other applications of clinical magnetocardiography are under evaluation. The use of the Relative smoothness index needs, in our opinion, a larger experience to define its reliability as a predictor of risk for sudden death. MCG follow-up study of patients with transplanted hearts seems to be a promising application, for early detection of acute graft rejection reaction. Our reported case strongly supports this potentiality. Present work is also addressed to develop an integrated system allowing easy MCG mapping during cardiac catheterization, as a new method to guide diagnostic and therapeutic procedures as close as possible to the arrhythmogenic substrate.

[Paraneoplastic porphyria cutanea tarda in a case of small cell bronchogenic carcinoma]. / Porfiria cutanea tarda paraneoplastica in un caso di carcinoma broncogeno a piccole cellule.

A case of diffuse hepatic metastasis of small cell bronchial carcinoma is presented. The first symptoms were specific PCT lesions and excessive excretion of urinary porphyrins. The patient was subjected to various instrumental examinations. Selective arteriography, CAT and hepatic echography showed liver to be of enormous size and completely homogeneous, suggesting a diagnosis of Budd-Chiari syndrome. Only hepatic scintigraphy showed multiple take-up lacunae and complete organ substitution. The rarity of the case and the possible pathogenesis of paraneoplastic PCT are discussed.