A key role for abdominal ultrasound examination in "difficult" diagnoses of celiac disease.

PURPOSE: To evaluate the usefulness of abdominal ultrasound examination (US) for the diagnostic workup of cases of suspected CD involving negative serum antibodies and difficult diagnosis. MATERIALS AND METHODS: 524 consecutive patients with symptoms of suspected CD underwent an extensive diagnostic workup. 76 (14 %) were excluded since they were positive for serum anti-tTG and/or EmA antibodies. 377 were excluded since they were diagnosed with something other than CD or did not have the alleles encoding for HLA DQ 2 or DQ 8. A diagnosis of CD with negative serum antibodies was probable in 71 patients who underwent abdominal US and duodenal biopsy for histology evaluation. RESULTS: Intestinal histology and subsequent clinical and histological follow-up confirmed the CD diagnosis in 12 patients (GROUP 1) and excluded it in 59 subjects (GROUP 2). Abdominal US showed that the presence of dilated bowel loops and a thickened small bowel wall had a sensitivity of 83 % and a negative predictive value (NPV) of 95 % in CD diagnosis. Furthermore, in 11 of the 12 CD seronegative patients there was at least one of these two abdominal US signs. Therefore, considering the presence of one of these two signs, abdominal US sensitivity increased to 92 % and NPV to 98 %. CONCLUSION: Abdominal US is useful in the diagnostic workup of patients with a high clinical suspicion of CD but with negative serology.

[Penal liability from retained foreign body inside the surgical site]. / La responsabilità penale da derelizione di corpo estraneo in sito chirurgico.

The Authors focus on the liability of the surgery team members in the case they inadvertently forget behind in the patient's body a foreign object, which causes injuries and/or death. The Authors underline that, according to the current case law regarding medical malpractice, both the main surgeon and their assistant/subordinate are liable for engaging in a markedly imprudent and/or negligent conduct, such as not double-checking scrupulously the surgical site before its closure in order to highlight forgotten foreign bodies. As well, the Authors underline that either the circulator nurse or the theatre nurse can be considered punishable by law when that medical error occurs, even if they are responsible for the count of the instruments used in the course of the surgery. Conversely, the main surgeon and his or her assistant are always directly responsible, due to the fact that the nurses' count procedure represents merely an additional control measure, without substituting at all the check the surgeons must obligatory conduct on the surgical site. Finally, the Authors point out that, as the count procedure is performed by the members of a surgical team, where a hierarchy-based relationship rules, the main surgeon is the liable for any preventable and avoidable adverse event provoked by the nursing staff as a consequence of the objective responsibility due to culpa in eligendo and culpa in vigilando.

Management of sodium-channel blocker poisoning: the role of hypertonic sodium salts.

Sodium-channel blockers act by slowing sodium influx into myocytes through voltage gated channels. Many substances have sodium-channel blocking properties and many others show this effect when taken in overdose. Sodium-channel blocker poisoning, associated with a high death rate, is characterized by a variety of clinical presentation, depending on the pharmaceutical agent involved. Sodium bicarbonate or lactate, increasing serum pH and extracellular concentration of the ion, displace the drug from its receptor sites and can be used for the treatment of cardiac toxicity in the setting of sodium-channel blocker poisoning. In spite of this theoretical assumption, the role played by hypertonic sodium salts is not well elucidated and conflicting results have been reported. Authors review the pathophysiologic mechanisms of sodium-channel blocker poisoning and the evidences in literature concerning the efficacy of hypertonic sodium salts in the treatment of the related toxicity.

Neutrophil gelatinase-associated lipocalin: a novel biomarker for the early diagnosis of acute kidney injury in the emergency department.

Acute kidney injury (AKI) is a common medical problem among critical patients. In current clinical practice, AKI is diagnosed by measuring serum creatinine concentration, which is an unreliable and delayed marker of the deterioration of kidney function. Its rise occurs when a significant amount of renal function has been lost. Many are the factors able to modify physiological levels, such as age, gender, ethnicity, dietary protein intake, muscle mass or metabolism, hydration status and drugs. Definitely, creatinine, as well as blood urea nitrogen (BUN) or urine markers of kidney injury (fractional excretion of sodium, urinary concentrating ability, casts), do not directly reflect cell injury, but rather the delayed functional consequences of the damage. Due to the lack of sensitive and specific biomarkers, the identification of early stages of AKI has been impossible but, recently, neutrophil gelatinase-associated lipocalin (NGAL) is emerging as a novel biomarker of AKI from several etiologies, such as cardiac surgery, contrast nephropathy, kidney transplantation and sepsis. This protein, produced in a number of human tissues and particularly in the distal nephron, has siderophore-chelating property and acts as an iron-trasporting shuttle. NGAL increases in both serum and urine 48 hours before the rise of creatinine, and shows a strong correlation with change in creatinine concentrations. An early diagnosis of AKI allows the early institution of therapeutic measures for the protection of renal function and improves the prognosis. This possibility is particularly important in the Emergency Department for the treatment of critical patients with potential nefrotoxic therapies. Use of NGAL as early marker of AKI in the Emergency Department is discussed.

[Gastrointestinal stromal tumors (GISTs). Personal experience on three cases of the tumors of the small intestine complicated and emergency surgically treated]. / I tumori stromali gastrointestinali (GIST). Esperienza personale su tre casi a localizzazione nel tenue mesenteriale trattati in urgenza.

INTRODUCTION: GISTs, a new nosological entity recently described, represent a peculiar model of solid tumor: the identification of the molecular mechanism responsible for the oncogenesis led to the development of a new drug (imatinib) active on the specific molecular target, represented by the product of the mutated proto-oncogene c-kit which is a tyrosine kinase receptor that becomes constitutively active by mutation. Surgical resection, nevertheless, is still the primary treatment and it has to be as complete as possible. These two treatments can be integrated. GISTs are not uniformly kit-positive, and they can be alternatively due to mutations of the PDGFRA gene or, in patients with neurofibromatosis type 1 (NF-1), to generally isolated mutations of the NF-1 gene. PATIENTS AND METHODS: We describe 3 cases of kit-positive GISTs of the small intestine (SISTs), complicated and emergency surgically treated: case 1--53 years, female, with small bowel obstruction and concomitant acute intestinal bleeding; case 2--71 years, male, with NF-1 and acute intestinal bleeding; case 3--47 years, male, with perforation of the Treitz tract. The first two cases have been treated with intestinal resection and immediate mechanical anastomosis; the third one with resection of the pedunculated tumor at its base, where is situated the perforation too. CONCLUSIONS: SISTs (20-30%), with little or no symptoms in the initial phases, show notable diagnostic difficulties. Their aspecific and late clinical presentation--typical of this site and of the pathology that we are talking about--and the difficult physical-instrumental approach to small bowel limit the possibility of an accurate diagnosis and expose the patient to potentially fatal acute complications and to risks related to emergency surgery treatment that decreases the possibility of a radical resection.

Oral mucosa of coeliac disease patients produces antiendomysial and antitransglutaminase antibodies: the diagnostic usefulness of an in vitro culture system.

BACKGROUND: Antiendomysial (EmA) and antitransglutaminase (anti-tTG) antibodies are the most specific indirect marker of coeliac disease (CD). It is not known whether the oral mucosa of patients with CD is able to produce these antibodies or not. AIMS: To evaluate the ability of the oral mucosa of patients with CD to produce antibodies in an in vitro culture system. PATIENTS AND METHODS: Twenty-eight patients with new diagnosis of CD (15 adults and 13 children) and 14 adult subjects with other diseases (controls) were studied. All underwent oral mucosa biopsy and subsequent EmA and anti-tTG assays on the mucosa culture medium. RESULTS: Sensitivity and specificity of EmA and anti-tTG assayed in the oral mucosa culture medium for CD diagnosis were 54% and 100% and 57% and 100%, respectively. The CD clinical presentation, such as the presence of oral mucosa lesions, did not influence the results of the EmA and anti-tTG assays in the oral mucosa culture medium. There was an association between positivity of antibodies and greater severity of the oral mucosa lymphocyte infiltration. CONCLUSION: This study demonstrates that the oral mucosa contributes to EmA and anti-tTG production in untreated patients with CD.

IgA anti-actin antibodies ELISA in coeliac disease: a multicentre study.

BACKGROUND: Previous studies have demonstrated that serum anti-actin antibodies are a reliable marker of intestinal damage severity in coeliac disease. AIMS: To validate in a multicentre study the clinical usefulness of serum IgA anti-actin antibody ELISA and its possible use in monitoring intestinal mucosa lesions during gluten-free diet. PATIENTS AND METHODS: Four centres recruited 205 newly diagnosed coeliac disease patients with villous atrophy, 80 healthy controls and 81 "disease" controls. Twelve coeliac disease patients on gluten-free diet but with persistent symptoms underwent serum IgA anti-actin antibody assay and intestinal histology evaluation. IgA anti-actin antibody ELISA was performed with a commercial kit. All coeliac disease patients underwent intestinal histology study. RESULTS: IgA anti-actin antibodies showed a sensitivity of 80% and a specificity of 85% in the diagnosis of coeliac disease patients with villous atrophy. The area under the receiving operator curve for anti-actin antibodies was 0.873 [95% C.I. 0.805-0.899]. Serum anti-actin antibodies values were significantly higher in coeliac disease patients than in healthy or "disease" controls (P<0.0001). Serum anti-actin antibodies were positive in 41 of the 60 coeliac disease patients with mild intestinal histology lesions (69%) and in 123 of the 145 with severe lesions (85.3%) (P<0.05). There was a significant inverse correlation between anti-actin antibody values and the villi/crypts ratio (r=-0.423; P<0.0001). In the 12 coeliac disease patients on gluten-free diet who underwent re-evaluation as they were persistently symptomatic, intestinal histology showed three cases with persistent villous atrophy: all of these were positive for serum anti-actin antibodies ELISA, whereas both serum anti-tTG and EmAs were negative. The other nine patients showed normal intestinal villi and were negative for serum anti-actin antibodies. CONCLUSIONS: Anti-actin antibodies are a reliable marker of severe intestinal mucosa damage in coeliac disease patients and a simple ELISA technique offers an accurate method for their determination. These antibodies seem to be a very reliable marker of persistent intestinal damage in coeliac disease patients.

Full-beam performances of a PET detector with synchrotron therapeutic proton beams.

Treatment quality assessment is a crucial feature for both present and next-generation ion therapy facilities. Several approaches are being explored, based on prompt radiation emission or on PET signals by [Formula: see text]-decaying isotopes generated by beam interactions with the body. In-beam PET monitoring at synchrotron-based ion therapy facilities has already been performed, either based on inter-spill data only, to avoid the influence of the prompt radiation, or including both in-spill and inter-spill data. However, the PET images either suffer of poor statistics (inter-spill) or are more influenced by the background induced by prompt radiation (in-spill). Both those problems are expected to worsen for accelerators with improved duty cycle where the inter-spill interval is reduced to shorten the treatment time. With the aim of assessing the detector performance and developing techniques for background reduction, a test of an in-beam PET detector prototype was performed at the CNAO synchrotron-based ion therapy facility in full-beam acquisition modality. Data taken with proton beams impinging on PMMA phantoms showed the system acquisition capability and the resulting activity distribution, separately reconstructed for the in-spill and the inter-spill data. The coincidence time resolution for in-spill and inter-spill data shows a good agreement, with a slight deterioration during the spill. The data selection technique allows the identification and rejection of most of the background originated during the beam delivery. The activity range difference between two different proton beam energies (68 and 72 MeV) was measured and found to be in sub-millimeter agreement with the expected result. However, a slightly longer (2 mm) absolute profile length is obtained for in-spill data when compared to inter-spill data.

Delayed and fast transient potassium currents in rat neocortical neurons in cell culture.

Cultured rat neocortical neurons were subjected to the whole-cell mode of voltage clamping to study outward K+ currents. Tetrodotoxin and Cd2+ were applied extracellularly to block Na+ and Ca2+ currents. Depolarizing voltage commands from a holding potential of -90 mV evoked an outward current which peaked early and decayed over 20-50 ms to attain a steady level. At holding potentials more positive than -50 mV, the fast, transient component of the outward current was largely inactivated while the late, steady one remained present. The two components of the outward current displayed different pharmacological sensitivities: the fast, transient one was blocked by 4-aminopyridine, while the late, persistent one was reduced by tetraethylammonium. These currents were present in neocortical cells as early as the third day in culture. Our experiments indicate that as in sympathetic, hippocampal and spinal cord neurons, neocortical cells possess both a fast, transient, and a delayed K+ current. These currents might play an important role in controlling neocortical excitability.

Vitamins A and E in neoplastic disease.

Vitamins A and E play an important role against 'free radicals' (FRs). Their antioxidant action is evident in neoplastic disease (ND) that is known to have a FRs pathology. This finding has been supported by previous research showing increased lipid peroxidation of the erythrocyte membrane with increased permeability and higher hemoglobin susceptibility to oxidative stress. Connections exist between the two vitamins and FRs lipid peroxidation of the membranes. In order to study A and E vitamin behaviour in ND, they were assayed in the sera of 88 cancer patients versus 94 healthy subjects. In the 88 cancer cases, without considering variables such as age, sex and smoking habits, the average amount of vitamin A was 47.44+/-19.60 mu g/dl versus 71.77+/-18.30 in controls (P<0.0001). The average amount of vitamin E was 1144.42+/-507.45 in ND versus 1497.45+/-397.74 in controls (P<0.0001). The two vitamins were simultaneously assayed in the same serum by high pressure liquid chromatography. The method is rapid and gave exact and repeatable results. Reasons for vitamin decrease are discussed.

Free radical erythrocyte damage in tumoral disease assessed by He-Ne laser and optical microscope through "Heinz Bodies" method.

Results obtained from blood sample readings by optical microscopy and He-Ne laser (lambda = 630.1 mW), have confirmed the reduction in Heinz Bodies (HB) formation time and the Transmittance Reduction Degree (TRD), in malignancies. The results of spectrometric readings in colorectum polyposis, (TRD = 0.07) and fibrocystic mastopathy (TRD = 0.08) gave results overlapping with controls (TRD = 0.08). In neoplasias, the early HB formation in erythrocytes observed by optical microscope corresponded to TRD increase = 0.17 (P < 0.01). TRD increase was statistically significant (P < 0.01), as well as the reduction in the time of HB appearance (< 0.01). The relationship between optical and laser readings was exponential in tumors, while it was linear in controls, in polyposis and mastopathies. The values of the correlation coefficients obtained by both methods were significant (P < 0.01) for all the studied groups. Moreover, these research data further support the existence, even in the earlier stages of the disease, of the labile state of the red cell membrane due to strong lipid peroxidation by FRs.

The vesical granuloma: rare and late complication of laparoscopic cholecystectomy.

The spillage of gallstones into the peritoneal cavity from iatrogenic perforation of the gallbladder that occurs during laparoscopic cholecystectomy can result in late and serious complications. We report a case of vesical granuloma with symptoms of dysuria, pollakiuria, and vesical tenesmus that occurred 23 months after a laparoscopic cholecystectomy. Preoperative diagnostic evaluation showed a 3-cm vesical neoformation. A partial cystectomy was performed; macroscopic and histologic examination documented a central nidus of fragmented gallstones and a picture of chronic granulomatous inflammation. Although complications related to unretrieved gallstones that spill into the peritoneal cavity during laparoscopic cholecystectomy are rare, they are being reported with increasing frequency. Therefore, it is important to use tools and techniques that prevent lacerations of the gallbladder and involve retrieval of spilled gallstones.

[Anterior inguinal hernioalloplasty by the modified Valenti's technique. Preliminary results of our experience]. / Ernioalloplastica inguinale per via anteriore secondo la tecnica di Valenti modificata. Risultati preliminari della nostra esperienza.

The authors dwell upon the deep changes which the surgery of the inguinal hernia has recorded in the last years with the aim to reduce the rate of relapses and based on the philosophy tension free repair, particularly on the prosthetic patch and plug hernioplastics which represent the evolution of this concept and among these must be includes the D.SR.P. and flat plug hernia repair, that they have set with a sort of eclecticism and of integration of some of the operation times of Valenti's and Trabucco's methodologies and of some prosthetic protections used by themselves. Then, they dwell upon the rational of the variant in the Valenti's original technique put forward them, and this variant arise from a critical testing, they perform their preliminary clinic experience about primitive inguinal hernia repair through the methodology that has been proposed, then they declare that they can confirm it from the point of view of the effectiveness and safety only after further confirmations based on far wider surveys and on longer "follow-up" and after an objective comparison between this one and the two methods of whom it forms the technical compromise.

Pyoderma gangrenosum of the "sinus mammarum" in ulcerative colitis.

The first part of this article deals with the report of a patient suffering from pyoderma gangrenosum of the "sinus mammarum" associated with asymptomatic ulcerative colitis. This is followed by a revision of the present epidemiological, etiological, pathogenetic and clinical knowledges about this systemic manifestation of chronic phlogosis of the colon. The Authors have analysed the treatment for this condition and emphasized the resistance of the cutaneous ulcer encountered to conventional medical therapy of the underlying colonic disease which proved to be efficacious only on the latter; this led to integrate traditional treatment with the use of perilesional injections of small doses of calcic heparin as an alternative to immunosuppressive drugs or surgery. Topical antithrombotic treatment, which can be justified by the histological findings of phenomena of the vasculitis in the edge of pyoderma gangrenosum, demonstrated to be crucial and represents a peculiarity in the case here reported, which is unique in the literature as far as the Authors know, since it has not been experimented by anyone else.

Proton range monitoring with in-beam PET: Monte Carlo activity predictions and comparison with cyclotron data.

GOAL: Proton treatment monitoring with Positron-Emission-Tomography (PET) is based on comparing measured and Monte Carlo (MC) predicted ß(+) activity distributions. Here we present PET ß(+) activity data and MC predictions both during and after proton irradiation of homogeneous PMMA targets, where protons were extracted from a cyclotron. METHODS AND MATERIALS: PMMA phantoms were irradiated with 62 MeV protons extracted from the CATANA cyclotron. PET activity data were acquired with a 10 × 10 cm(2) planar PET system and compared with predictions from the FLUKA MC generator. We investigated which isotopes are produced and decay during irradiation, and compared them to the situation after irradiation. For various irradiation conditions we compared one-dimensional activity distributions of MC and data, focussing on Δw50%, i.e., the distance between the 50% rise and 50% fall-off position. RESULTS: The PET system is able to acquire data during and after cyclotron irradiation. For PMMA phantoms the difference between the FLUKA MC prediction and our data in Δw50% is less than 1 mm. The ratio of PET activity events during and after irradiation is about 1 in both data and FLUKA, when equal time-frames are considered. Some differences are observed in profile shape. CONCLUSION: We found a good agreement in Δw50% and in the ratio between beam-on and beam-off activity between the PET data and the FLUKA MC predictions in all irradiation conditions.

Potassium currents in rat cortical neurons in culture are enhanced by the antiepileptic drug carbamazepine.

We report that carbamazepine (Tegretol), a drug that is useful for the treatment of complex partial seizures, enhances outward, voltage-dependent K+ currents generated by rat neocortical cells in culture and recorded with patch-clamping techniques. This effect is seen in the presence of therapeutic concentrations of carbamazepine (10-20 microM). Furthermore, at these doses carbamazepine does not influence voltage-dependent inward Na+ and Ca2+ currents recorded in these cells. The action exerted by carbamazepine on K+ currents is a novel finding and might represent an important mechanism for controlling neocortical excitability and thus the generation of epileptiform activity.