Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study.

BACKGROUND: As studies on gastrointestinal neuroendocrine carcinoma (WHO G3) (GI-NEC) are limited, we reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. PATIENTS AND METHODS: Data from advanced GI-NEC patients diagnosed 2000-2009 were retrospectively registered at 12 Nordic hospitals. RESULTS: The median survival was 11 months in 252 patients given palliative chemotherapy and 1 month in 53 patients receiving best supportive care (BSC) only. The response rate to first-line chemotherapy was 31% and 33% had stable disease. Ki-67<55% was by receiver operating characteristic analysis the best cut-off value concerning correlation to the response rate. Patients with Ki-67<55% had a lower response rate (15% versus 42%, P<0.001), but better survival than patients with Ki-67≥55% (14 versus 10 months, P<0.001). Platinum schedule did not affect the response rate or survival. The most important negative prognostic factors for survival were poor performance status (PS), primary colorectal tumors and elevated platelets or lactate dehydrogenase (LDH) levels. CONCLUSIONS: Advanced GI-NEC patients should be considered for chemotherapy treatment without delay.PS, colorectal primary and elevated platelets and LDH levels were prognostic factors for survival. Patients with Ki-67<55% were less responsive to platinum-based chemotherapy, but had a longer survival. Our data indicate that it may not be correct to consider all GI-NEC as one single disease entity.

Test of "crab-waist" collisions at the DAPhiNE Phi factory.

The electron-positron collider DAPhiNE, the Italian Phi factory, has been recently upgraded in order to implement an innovative collision scheme based on large crossing angle, small beam sizes at the crossing point, and compensation of beam-beam interaction by means of sextupole pairs creating a "crab-waist" configuration in the interaction region. Experimental tests of the novel scheme exhibited an increase by a factor of 3 in the peak luminosity of the collider with respect to the performances reached before the upgrade. In this Letter we present the new collision scheme, discuss its advantages, describe the hardware modifications realized for the upgrade, and report the results of the experimental tests carried out during commissioning of the machine in the new configuration and standard operation for the users.

Different carbon sources affect lifespan and protein redox state during Saccharomyces cerevisiae chronological ageing.

In this study, a proteomic approach that combines selective labelling of proteins containing reduced cysteine residues with two-dimensional electrophoresis/mass spectrometry was used to evaluate the redox state of protein cysteines during chronological ageing in Saccharomyces cerevisiae. The procedure was developed on the grounds that biotin-conjugated iodoacetamide (BIAM) specifically reacts with reduced cysteine residues. BIAM-labelled proteins can then be selectively isolated by streptavidin affinity capture. We compared cells grown on 2% glucose in the exponential phase and during chronological ageing and we found that many proteins undergo cysteine oxidation. The target proteins include enzymes involved in glucose metabolism. Both caloric restriction and growth on glycerol resulted in a decrease in the oxidative modification. Furthermore, in these conditions a reduced production of ROS and a more negative glutathione half cell redox potential were observed.

Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study.

BACKGROUND: Recent studies suggest a role of n-3 long-chain polyunsaturated fatty acids (n-3 PUFA) as peroxisome proliferator-activated receptor-alpha ligands in improving non-alcoholic fatty liver disease (NAFLD) in rodents. However, data in humans are still lacking. AIM: To evaluate the efficacy of prolonged PUFA supplementation in patients with NAFLD. METHODS: Fifty-six patients with NAFLD were enrolled. Among the overall eligible patients, 42 assumed n-3 PUFA 1-g capsule daily for 12 months, whereas 14 refused the treatment and were analysed as controls. All patients underwent haematochemical and ultrasound follow-up. RESULTS: Polyunsaturated fatty acid supplementation significantly decreased serum aspartate transaminase (P = 0.003), alanine transaminase (P = 0.002), gamma-glutamyl transpeptidase (P = 0.03), triglycerides (P = 0.02) and fasting glucose (P = 0.02) in comparison with controls. Circulating arachidonate and n-6/n-3 fatty acid ratio was reduced (P = 0.0002, and P = 0.0001 respectively) in treated patients. Moreover, ultrasonography demonstrated improvement of liver echotexture after PUFA (P = 0.0001), and increase of Doppler perfusion index (P = 0.001), whereas no significant changes occurred in controls. CONCLUSIONS: Supplementation with n-3 PUFA improves biochemical, ultrasonographic and haemodynamic features of liver steatosis. Our study supports the efficacy of n-3 PUFA as a new therapeutic approach in the treatment of NAFLD.

Efficacy and safety of Palmaz stent implantation in the treatment of renal artery stenosis in renal transplantation.

To verify the long-term efficacy and safety of Palmaz stent implantation in the treatment of transplant renal artery stenosis (TRAS), we reviewed the charts of 26 patients affected by TRAS and treated by percutaneous transluminal angioplasty (PTA) followed by permanent insertion of a Palmaz stent. The mean follow-up period was 43.31 +/- 33.6 months. The mean blood pressure fell significantly at 1 month after stenting (118 +/- 8.1 vs 101 +/- 7.8 mmHg; P < .0001); then remained stable. Renal artery blood flow, as determined by Doppler ultrasonography, was reduced from 352.5 +/- 56.5 to 157.3 +/- 53.7 cm/sec at 1 month after stenting (P < .0001). Renal function improved after stenting (serum creatinine 2.2 +/- 1.4 mg/dL preinsertion versus 1.72 +/- 1.05 at 3 years). In conclusion, in cases of severe or recurrent TRAS, stenting of the renal artery has proved to be an effective therapeutic tool. This method, which has low procedure costs and an extremely low complication rate has proved to be safe and to offer the potential of preserving luminal patency, improving the long-term efficacy of percutaneous angioplasty.

Individualised headband simulation test for predicting outcome after percutaneous bone conductive implantation.

Trans-cutaneous bone conduction (BC) stimulators, when coupled to the HB (BC-HB), are generally used to predict the results that could be achieved after bone conductive implant (BCI) surgery, and their performance is generally considered inferior to that provided by the definitive percutaneous system. The aim of the present study was to compare the performances between BC-HB and BCI of the same typology, when the former's sound processor is fitted in accordance to the individual auditory situation. Twenty-two patients selected for surgical application of a BCI were evaluated and the same audiological protocol was used to select the candidate and assess the final outcome. The BC-HB was properly fitted based on individual hearing loss and personal auditory targets, and tested as primary step of the protocol to obtain the most reliable predictive value. The BAHA Divino and BP100 sound processors were applied in 12 patients with conductive/mixed hearing loss (CMHL) and in 10 subjects with single sided deafness (SSD). Audiometric evaluation included the pure tone average (PTA3) threshold between 250-1000 Hz; the PTA thresholds at 2000 and 4000 Hz; intelligibility scores as percentage of word recognition (WRS) in quiet and in noise; and subjective evaluation of perceived sound quality by a visual analogue scale (VAS). Statistical evaluation with a student's t test was used for assessment of efficacy of BC-HB and BCI compared with the unaided condition. Spearman's Rho coefficient was used to confirm the reliability of the BC-HB simulation test as a predictor of definitive outcome. The results showed that the mean PTA difference between BCI and BC-HB ranged from 2.54 to 8.27 decibels in the CMHL group and from 1.27 to 3.9 decibels in the SSD group. Compared with the BC-HB, BCI showed a better WRS both in CMHL (16% in quiet and 12% in noise) and in SSD (5% in quiet and a 1% in noise) groups. Spearman's Rho coefficient, calculated for PTA, WRS in quiet and in noise and VAS in the two aided conditions, showed a significant correlation between BC-HB and BCI, between PTA and VAS and between WRS in quiet and VAS. It is possible to conclude that the headband test, when the sound processor of the selected bone conductive implant is fitted and personalised for individual hearing loss and auditory targets of the candidate, may provide highly predictive data of the definitive outcome after BCI implant surgery.

Carrier priming with CRM 197 or diphtheria toxoid has a different impact on the immunogenicity of the respective glycoconjugates: biophysical and immunochemical interpretation.

Glycoconjugate vaccines play an enormous role in preventing infectious diseases. The main carrier proteins used in commercial conjugate vaccines are the non-toxic mutant of diphtheria toxin (CRM197), diphtheria toxoid (DT) and tetanus toxoid (TT). Modern childhood routine vaccination schedules include the administration of several vaccines simultaneously or in close sequence, increasing the concern that the repeated exposure to conjugates based on these carrier proteins might interfere with the anti-polysaccharide response. Extending previous observations we show here that priming mice with CRM197 or DT does not suppress the response to the carbohydrate moiety of CRM197 meningococcal serogroup A (MenA) conjugates, while priming with DT can suppress the response to DT-MenA conjugates. To explain these findings we made use of biophysical and immunochemical techniques applied mainly to MenA conjugates. Differential scanning calorimetry and circular dichroism data revealed that the CRM197 structure was altered by the chemical conjugation, while DT and the formaldehyde-treated form of CRM197 were less impacted, depending on the degree of glycosylation. Investigating the binding and avidity properties of IgGs induced in mice by non-conjugated carriers, we found that CRM197 induced low levels of anti-carrier antibodies, with decreased avidity for its MenA conjugates and poor binding to DT and respective MenA conjugates. In contrast, DT induced high antibody titers able to bind with comparable avidity both the protein and its conjugates but showing very low avidity for CRM197 and related conjugates. The low intrinsic immunogenicity of CRM197 as compared to DT, the structural modifications induced by glycoconjugation and detoxification processes, resulting in conformational changes in CRM197 and DT epitopes with consequent alteration of the antibody recognition and avidity, might explain the different behavior of CRM197 and DT in a carrier priming context.

Blood pressure response to exercise in young subjects with and without parental history of hypertension.

We examined 150 young male adults in the Italian Air Force to evaluate the correlation between blood pressure (BP) response to bicycle exercise and early structural changes of the left ventricle and the carotid arteries. The subjects were divided into three subgroups: (1) borderline hypertensives; (2) normotensives having one or both parents with hypertension; (3) normotensives without family history of hypertension. All subjects underwent a submaximal exercise test, echocardiography and carotid ultrasonographic study. The echocardiographic examination showed no significant difference between the three subgroups, while the vascular ultrasonographic examination showed a significant difference in carotid thickness between borderline hypertensives and the two other groups. The exercise test induced an abnormal hypertensive response only in the borderline group. We also considered the variation of systolic BP between maximum stress and the 1st, 3rd, 5th and 8th minute of recovery phase. From our data it seems that more than the exercise test, recovery BP values may be suggestive of an exaggerated cardiovascular response.

Effects of plasma exchange (PE) in primary biliary cirrhosis (PBC). A pilot study.

Six patients were studied to evaluate the efficacy and safety of plasma exchange (PE) in the treatment of primary biliary cirrhosis (PBC). All patients were affected by PBC at stage III-IV and presented symptoms refractory to pharmacologic therapy. Patients underwent PE for a mean period of 40 weeks (range 10-88). A mean of 33 liters (range 17-64) of plasma per patients was removed. Patients reported less fatigue (4/6), pruritus (5/5), nausea (3/3), Sjogren's syndrome (2/6), and painful neuropathy (2/3). A reduction of xanthomata was noted in one of the three affected patients. Definitive improvement was seen in the patient with Raynaud's phenomenon. A significant reduction was noted for serum cholesterol and gammaglobulins. ALT, AST, gamma-GT, alkaline phosphatase, bilirubin, prothrombin activity, AMA titers were not affected by PE. All patients suffered some mild adverse effects during PE. Two patients (IV stage) developed late edema and ascites after 34 and 44 weeks of treatment. We conclude that PE can be considered effective chronic treatment for advanced symptomatic PBC refractory to pharmacological therapy.

The central role of the endothelium in the pathogenesis of vasculitides.

The pathogenesis of vasculitides is poorly understood. A growing body of evidence indicates that endothelium injury is a fundamental step in the development of all types of vasculitides. In the recent years, it has become evident that endothelial cell is responsible for a multiplicity of functions such as several immunological activities and the control of the vascular tone. The alteration of endothelium may result in metabolic and biologic disorders leading to pathologic changes. Even though the importance of endothelial cell is now demonstrated, the pathophysiological mechanisms able to induce the vascular damage are still not completely defined. In the next years, the better knowledge of the physiology of the endothelium might lead to a more appropriate therapy of vasculitis.

[Oxolinic acid treatment of urinary sepsis in patients with renal insufficiency]. / Trattamento con l'acido ossolinico delle sepsi urinarie nei pazienti con insufficienza renale.

The effect of oxolinic acid, administered at the rate of 750 mg twice/day, has been studied on 31 patients with urinary tract infections. Many of them had a marked impairment of renal function due to nephropathies of various origin. Favourable results, with sterile urine and complete remission of symptoms, were obtained in 73.3%. Patients who were resistant to previous different therapies, were successfully treated. Oxolinic acid was on the whole well tolerated and proved to be effective also in patients with impaired renal function. In some of the latter an improvement in renal function occurred as a result of the effective urinary infection care. The tolerability of oxolinic acid was good: only one patient interrupted the treatment because of insomnia; other 4 had transient and mild side-effects.

[Effect of menstrual cycle on the immune response to surgical stress]. / Effetto del ciclo mestruale sulla risposta immunitaria all'aggressione chirurgica.

The Authors have studied the effects of different surgical interventions on some factors of humoral and cell-mediated immuno-competence: 112 premenopausal women, operated on mainly for benign conditions, have been considered in order to evaluate the influence of various phases of menstrual cycle on surgical immunosuppression. Two schemes were used to stratify the study sample: in the first analysis, we have subdivided the patients in 59 cases in perimenstrual phase (0 through 6 and 21 through 36 days from last menstrual period, LMP) and 53 in periovulatory (7-20 days from LMP). The second stratification relied on the hormone-dependent phases determined by the putative time of ovulation 14 days after LMP: 51 cases in follicular phase and 61 cases in luteal phase have been considered. Immune parameters have been evaluated before surgery and the day after intervention. The first comparison stresses the worst outcome of immune parameters in patients operated on in the perimenstrual period (CD4, activated lymphocytes and C3 have significantly reduced post-operatively). The second part of the study shows no significant difference in the two groups as to such parametres.

[Cancerous colonic polyps]. / Polipi cancerizzati del colon.

The treatment of cancerous polyps of the colon has not been definitely established. In the present study the authors have brought forth their contribution on the role played by endoscopic polypectomy alone or following a surgical resection. At our endoscopic service during the period from 1985 to 1992, there were 42 polyps diagnosed which after histologic examination showed an infiltrating carcinoma. 22 patients underwent surgery and 16 only an endoscopic polypectomy. The median follow-up was 43.3 months with a minimum period of 18 months. Four patients were lost during follow-up. We have analyzed for prognostic reasons, the type of polyps, the radicality of the polypectomy, the degree of differentiation and the infiltration of lymphatic and/or venous vessels of the polyp. The presence of carcinomal residue and lymphonodal metastases were taken into consideration in patients who underwent surgical resection. The results obtained were not evaluated statistically because of the limited number of patients with an adequately long follow-up. Nevertheless they are in line with those results from the majority of the cases quoted in other literature. In particular these cases which seem to have a favorable prognosis are those in which complete endoscopic polypectomy has coupled with a good degree of differentiation and the absence of infiltration of the lymphatic and venous vessels. In these cases surgery does not seem to have bettered the survival rate.

[A rare case of primary abdominal actinomycosis]. / Un raro caso di actinomicosi addominale primitiva.

The authors describe a case of primary abdominal actinomycosis operated on because of peritonitis sustained by a tubo-ovarian abscess. They discuss the pathogenesis of the case: the patient had been on intrauterine device contraception till two months earlier and had been operated on for breast cancer. Preoperative diagnosis is quite impossible and only the microscopic observation of the specimen can show the causative agent. Surgical options are reported, stressing the need for an adequate period of antimicrobial therapy.

PIP: In September 1993 a 43-year-old female patient with cancer underwent left mastectomy followed by immediate reconstruction. 6 days passed without problems, but then she presented at the emergency ward with abundant exudation of serous material from the cicatrices. Microbiological test showed evidence of Staphylococcus epidermitis. Drainage of the skin and smooth muscle was performed and the secretion was immediately reduced and seemed to disappear in a short time. In the next 3 days fever arose accompanied by abdominal pain. Blood test showed leucocytosis (24,500 GB), increase of the suppressor lymphocytes (CD8) and the reduction of CD4/CD8 ratio. Abdominal-pelvic echogram showed evidence of an enlarged right adnexum as well as that of the homolateral tube, but no discharge of fluid in the pelvic cavity. Gynecological examination in this patient, who had worn an IUD two months prior, excluded lesions in the portio or vagina and the vaginal flora did not show fungi or parasites. Diagnostic laparoscopy followed, which demonstrated in the pelvic cavity a large para-uterine tumefaction. The pelvic organs were adhering to the parietal layer of the peritoneum and in the whole peritoneal cavity, including the interhepatic-diaphragmatic space, fibrin plaque and pus was observed. Laparotomy was performed, which confirmed a parauterine mass and a tubo-ovarian complex with numerous recesses containing fetid, grayish pus. Complete right adnexectomy was carried out with abundant lavage and multiple drainage of the peritoneal cavity. Subsequently, the abdominal situation improved, but a new examination of drained liquid showed the presence of cutaneous bacterial flora but no fungi or parasites. Ovarian actinomycotic abscess with acute peritonitis and salpingitis was demonstrated. Subsequent antibiotic therapy consisted of piperacilline for 15 days, and 4 months after the episode the patient was well without return of the foci of infection.

Telemedicine for airline passengers, seafarers and islanders.

Airline passengers, seafarers and islanders are three different examples of people who can benefit from telemedicine. However, the peculiar characteristics of each group require different applications. In 60 years of activity, the CIRM has assisted more than 37,000 patients. In the 10 years from 1986 to 1996 the Centre provided radio medical assistance to 7647 patients, of whom 6981 (91.3%) were sailors, 642 (8.4%) were people living in isolated areas (small italian islands) with few medical facilities, while only 24 patients (0.3%) were airline passengers. In the same period, the telecommunication service received or transmitted almost 80,000 medical messages.