Taking advantage of viral immune evasion: virus-derived proteins represent novel biopharmaceuticals.

In healthy individuals, natural and adaptive immune responses are able to control virus entry into the host. In particular, CD8(+)-mediated cytotoxicity, sustained by the intervention of CD4+ cells, represents the major key event leading to virus eradication. On the other hand, viruses are able to evade from host immune response via several mechanisms, and special emphasis will be placed on hepatitis C virus and chronic Epstein-Barr infections also in view of personal data. Virokines, viroreceptors, and serpins greatly contribute to viral immune escape, and, among virokines, interleukin (IL)-10 has been object of intensive studies. Finally, all these products have been used as biopharmaceuticals, and, for instance, viral IL-10, chemokine-binding proteins, and serpins exhibit in animal models immunosuppressive, anti-inflammatory, and antiatherogenic activities. As far as their use in human trials is concernded, many cautions are required in order to avoid deleterious side effects and, in particular, the purity of the product, its route and frequency of administration, as well as the immune status of the patient should be taken into serious account.

Effect of sample volume location on Doppler-derived transmitral inflow velocity values in 288 normal subjects 20 to 80 years old: an echocardiographic, two-dimensional color Doppler cooperative study.

The aims of the study were to evaluate in a population of 288 normal subjects 20 to 80 years old (1) the normal values of the indexes of the mitral flow velocity pattern measured either at the tips of the mitral leaflets or at the annulus; (2) whether there was a significant difference between the values obtained at the tips compared with those measured at the mitral annulus; (3) the correlation with aging between the indexes measured in the two different positions; and (4) whether certain physiological variables have different effects on diastolic function measured in the two different positions. The highest values were always measured at the tips of the mitral leaflets (p < 0.05); only atrial filling fraction, E acceleration time, and E deceleration velocity had higher values when measured at the level of the annulus (p < 0.05). The A-wave peak velocity had the same mean value when measured at both the tips and at the annulus. A significant difference in the correlation between parameters measured at the tips of the mitral leaflets with age and at the annulus (with age) was observed for the following parameters: (1) peak E velocity, E integral, total integral and E acceleration showed better correlation with age when measured at the annulus (p < 0.02); (2) peak A velocity and A integral showed better correlation with age when measured at the tips of the mitral leaflets (p < 0.001). Multivariate analysis showed that age was the variable that had the most influence on diastolic function parameters; heart rate had less influence on the diastolic function indexes.

Use of macroporous polypropylene filter to allow identification of bacteria by PCR in human fecal samples.

The detection of pathogenic bacteria directly in human fecal specimens by PCR, requires removal of PCR-inhibitory substances. To investigate whether five different macroporous filters (polypropylene, nylon, polyester, polyethylene, fluorocarbon) could retain polysaccharides, major PCR inhibitors, an in vitro model and human fecal samples were used. The in vitro model consisted of Xanthum gum solutions (3 mg/ml PBS), a bacterial polysaccharide, to which Helicobacter pylori cells were added. Fecal samples from healthy volunteers were spiked with H. pylori and Mycobacterium paratuberculosis cells. Polysaccharide concentrations were significantly reduced only by the polypropylene but not by the other filters. Accordingly, both Xanthum gum solutions and spiked fecal specimens became PCR positive only after filtration with the polypropylene filter. We conclude that this filter can be used to prepare a bacterial DNA template suitable for PCR analysis from human feces.

Does aortic regurgitation affect transmitral flow? An echo-Doppler study.

Recent studies suggest that the presence of aortic regurgitation can interfere with Doppler measurement of mitral pressure half-time in patients with mitral stenosis. Amongst the factors affecting the transmitral flow in aortic regurgitation a putative role may be played by the mechanical hit of the aortic regurgitant jet impinging on the anterior mitral leaflet, as is very often seen with Doppler Color Flow examination. This study was designed to evaluate the effects of pure aortic regurgitation on the transmitral flow in patients with normal mitral valves. We studied 35 patients affected by pure chronic aortic regurgitation but with a normal mitral valve and compared them with 30 normal subjects. In all the patients the aortic regurgitant jet was directed toward the anterior mitral leaflet. In all the patients and control subjects a standard echo-Doppler examination was performed, sampling the transmitral flow at the level of the tip of the mitral leaflets. In 7 patients and 11 normal subjects the transmitral flow was also sampled at the level of the mitral annulus. Patients with aortic regurgitation showed significantly higher values of the mitral pressure half-time (61.04 +/- 15.14 vs 50.59 +/- 7.07 ms, P < 0.05) and of the time-velocity integral of the total transmitral flow, while the other parameters of transmitral flow, the mitral annulus diameter and the mitral stroke volume didn't show statistically significant differences. The comparison of the pressure half-time and time-velocity flow values measured at the level of the mitral annulus between patients and normal subjects didn't show significant differences.(ABSTRACT TRUNCATED AT 250 WORDS)

[Selective use of intra-operative cholangiography in gallstone surgery]. / L'impiego selettivo della colangiografia intraoperatoria nella chirurgia della calcolosi biliare.

The authors report their experience of the use of intraoperative cholangiography in 350 operations for biliary stones. The cholangiography was performed on all 52 patients with preoperative diagnosis of stones in CBD. In the 298 patients with gallbladder stones intraoperative colangiography was performed in 32 times, on the basis of previous jaundice, pancreatitis, microlithiasis, enlarged cystic duct or choledochus, and suspected palpatory reports of hepatic duodenal ligament. Intraoperative colangiography showed stones in all the patients of the first group and in 8 (25%) of the second. No patients reported disturbances attributable to residual stone with an average follow-up of 6 months.

An uncommon cause of pericardial actinomycosis.

Cardiac actinomycosis is rare; the pericardium is the most frequently involved site, but myocardial, endocardial and valvular involvement have all been documented. Most cases originate from a thoracopulmonary site of actinomycosis and spread directly to the pericardium. Widespread dissemination from extrathoracic organs is uncommon; in fact actinomycosis is prevented by anatomical barriers and hematogenous diffusion is rare. We describe an uncommon case of pericardial actinomycosis due to a draining fistula from the liver to the pericardial space across the diaphragm. The massive dissemination through the fistula could explain the peculiar echocardiographic images of macroscopic, echo-reflective, irregular masses, floating in the pericardial space, probably consistent with aggregates of sulfur granules.

[Current indications for esophageal transection with gastric devascularization in the treatment of hemorrhaging esophageal varices]. / Le attuali indicazioni alla transezione esofagea con devascolarizzazione gastrica nel trattamento delle varici esofagee sanguinanti.

When endoscopic sclerotherapy fails or after recurrence, a surgical approach is necessary. Oesophageal transection is a rational and effective option, because, compared to the shunt, it does not change hepatic haemodynamics, it has lower operative mortality, particularly in emergency, and it does not complicate the surgical technique of a subsequent liver transplant. The authors report their own experience of 12 patients undergoing oesophageal transection out of a total 148 treated with endoscopic sclerotherapy for bleeding oesophageal varices, over a 5 year period. 4 patients were operated in emergency and 8 after haemorrhagic recurrence, 5 because of advanced hepatopathy and 3, young and Child A, because they were potential candidates for a liver transplant. Operative mortality has been nil, morbidity about 40% and the mean postoperative stay 15.4 days (range 10-21). In a mean follow up of 30 months haemorrhagic recurrence was 16.6% (2 cases); 2 patients died respectively 26 and 40 months after surgery.

[The role of fine needle biopsy in the cytologic diagnosis of thyroid nodules]. / Il ruolo della citologia per aspirazione con ago sottile nella diagnosi dei noduli tiroidei.

The study was conducted an 298 patients suffering from thyroid nodules who underwent FNAB and successively surgery. The results of FNAB, compared with histology showed a sensibility of the technique of 76.6%, a specificity of 100%, an efficiency of 97.3%, with a negative prognostic value of 97% and a positive one of 100%. The authors stress the role of FNAB in the diagnosis of thyroid nodules in permitting, apart from where follicular tumours are concerned, an efficient identification of malignancy.

[The risk factors and prevention of recurrences in rectal surgery]. / Fattori di rischio e prevenzione delle recidive nella chirurgia del retto.

The authors report their own experience of 34 patients operated on for rectal cancer. In 8 cases abdomino perineal resection and in 26 anterior resection with anastomoses (6 in second time) were performed. Operatory mortality was nil and with an average follow up of 34 months 5 local recurrences were observed 16%. Among the risk factors examined the most important seems to be the stage of the disease; imperative it is therefore a correct surgical approach which warranted a significant reduction of local recurrences. This surgical approach includes a safety distal clearance from the tumour (at least 2.5 cm.), radical lymphadenectomy and complete removal of the mesorectum.

Is endoscopic injection hemostasis of bleeding gastrointestinal ulcers obsolete in 1995?

Bleeding non-neoplastic lesions of the upper gastrointestinal tract, not due to portal hypertension, are a frequent cause of emergency admission. In the present paper we report our retrospective experience in hemostatic injection treatment of these lesions. From May 1990 to May 1994, 164 patients were admitted to our institution for a bleeding gastrointestinal lesion. In 124 cases an ulcer classified according Forrest's criteria was detected. Four patients underwent immediate surgery. The second group of 86 patients (FIIa/FIIb/FIII) were treated conservatively. The third group of 34 patients (FIa/FIb/FIIa) underwent perilesional injection of adrenaline 1:10,000 and polidocanol 1% saline solution during endoscopic examination; 29% (25 pts) of the second group re-bled during the first 72 h vs 8.8% (3 pts) of the third group. The postoperative morbidity in the rebleeding patients was higher in the second group: 38.4% vs 0%. The importance of immediate, inexpensive, and simple hemostatic treatment extended to Forrest IIa lesions is emphasized.

[Coronary vasospasm secondary to subcutaneous administration of sumatriptan]. / Vasospasmo coronarico secondario a somministrazione sottocutanea di sumatriptan.

We present the case of a 38-year-old woman with no previous history of coronary heart diseases, who suffered from cluster headaches and had undergone a subcutaneous sumatriptan treatment for two years. With no previous history of underlying ischaemic heart diseases or Prinzmetal's angina or any other significant coronary diseases supported by an angiographic exam, the patient suffered from an episode of coronary vasospasm following a subcutaneous administration of sumatriptan. Therefore particular care should be placed when subcutaneous sumatriptan is administered to patients who experienced chest pain or other related symptoms after the use of the drug.

Left ventricular diastolic parameters in 288 normal subjects from 20 to 80 years old.

Left ventricular diastolic indexes are influenced by several variables. In order to evaluate the relationship of these indexes to age, heart rate, sex and to standard echo parameters, 288 normal subjects aged from 20 to 80 years, divided into six age groups, underwent a two-dimensional colour Doppler examination. Doppler examination was performed from the apical four chamber view to evaluate transmitral flow; isovolumic relaxation time (IVRT) was measured from an apical five chamber view. In order to obtain a sufficient number of subjects for an adequate statistical analysis, seven hospitals were involved in the study. Univariate analysis showed that age influences the peak velocity of the E (r = -0.46) and A waves (r = 0.46), the E/A ratio (peak velocities) (r = -0.69), the A wave integral (r = 0.48) and the E/A integral ratio (r = -0.57), the early and late filling fractions (r = -0.48 and r = 0.51 respectively), and the E wave deceleration (r = -0.43) and deceleration time (r = 0.36). In subjects older than 70 years an inversion of the E/A wave ratio was observed. Multivariate analysis confirmed that age has an important influence on left ventricular diastolic indexes but also demonstrated that heart rate has a significant influence. Sex, ejection fraction (EF), and the dimensions of the mitral annulus and the left ventricular posterior wall had less influence on left ventricular diastolic indexes. The mean values of E and A wave acceleration, deceleration and peak velocity were used to depict left ventricular filling morphology in various age groups for three different heart rate values. The conclusions of the study, are: (1) normal left ventricular diastolic parameters were obtained as mean values at seven different hospitals (2) when evaluating left ventricular diastolic function parameters it is important to take into account age and heart rate; E/A inversion in older subjects should be considered the normal mitral flow pattern.

Dobutamine echocardiography: usefulness of digital image processing.

The present study was undertaken in order specifically to evaluate the usefulness of digital image processing so as to enhance the diagnostic power of dobutamine stress echocardiography. For this purpose 44 dobutamine echocardiographic tests, routinely performed in our echo laboratory, were analysed blindly by two observers using traditional videotape recording and digitized image acquisition. The results obtained from both observers show a trend which suggests that the traditional videotape approach provides more true-positive tests than the digitized approach (27/38 vs 23/38 and 24/38 vs 22/38 for the first and second observer, respectively). True-negative test detection was 6/6 with the videotape and 5/6 with the digitized method for both observers. As a consequence of the discrepancies observed between the two modalities, the videotape indicates that it can provide higher diagnostic accuracy than the digitized approach (72 +/- 9% vs 63 +/- 10%). The tests results concordance (positive or negative) between the two modalities of analysis was 66% for both the observers. The inter-observer agreement on the test results was 84% and 80% for the videotape analysis and the digitized analysis, respectively. On the basis of the results, we consider that digitized analysis applied to dobutamine stress echocardiography does not afford significant diagnostic advantages and should not be considered as an alternative option to traditional videotape analysis. However, it may be considered an extremely useful integrative tool since it produces the on-line image evaluation more easily and faster and allows a more practical form of stress test storage.

Pulmonary venous flow velocity patterns in 143 normal subjects aged 20 to 80 years old. An echo 2D colour Doppler cooperative study.

In order to find out the normal values and to evaluate the effects of age, heart rate, sex, and haemodynamic and standard echocardiographic parameters on pulmonary venous flow velocity obtained by the transthoracic approach. Doppler pulmonary venous flow parameters were measured in 143 healthy subjects aged from 20 to 80 years. Doppler pulmonary venous flow parameters which had the best correlation with age were: the peak velocity of the systolic wave (r = 0.39) and its integral (r = 0.5), the peak velocity of the diastolic wave (r = -0.6) and its integral (r = -0.44); the systolic (r = 0.68) and diastolic fractions (r = -0.68); the systolic/diastolic peak velocity ratio (r = 0.73) and the systolic/diastolic integral ratio (r = 0.7). The atrial reversal wave did not correlate with age; the atrial reversal wave was more difficult and probably less reliable to measure than the systolic and diastolic waves. The correlations of pulmonary venous flow parameters with mitral flow parameters were also examined. This study showed that, in healthy subjects, despite an increase in the early and atrial waves from the annulus to the tips of the mitral leaflets, there is a similar association between pulmonary venous flow and mitral flow measured at the annulus or at the tips of the mitral leaflets. The intra-observer reproducibility of all the pulmonary venous flow parameters considered were found to be excellent. Moderate inter-observer variability was observed for the systolic, diastolic and atrial reversal wave peak velocities and integrals; however, the systolic/diastolic ratio improved the precision of the measurements. Multivariate analysis showed that age is the principal determinant of the Doppler parameters of pulmonary venous flow: heart rate, sex, body surface area, the size of the left atrium in systole and the left ventricular ejection fraction all influence the Doppler parameters of pulmonary venous flow, even if only slightly.