Search

Previous analyses of the GIM (Gruppo Italiano Mammella) 2 study showed that addition of fluorouracil to epirubicin, cyclophosphamide, and paclitaxel in patients with node-positive early breast cancer does not improve outcome, whereas dose-dense chemotherapy induces a significant improvement in both disease-free survival and overall survival as compared with a standard schedule. Here, we present long-term results of the study.In this 2 × 2 factorial, open-label, randomised, phase 3 trial, we enrolled patients aged 18-70 years with operable, node-positive, breast cancer with Eastern Cooperative Oncology Group performance status of 0-1 from 81 hospitals in Italy. Eligible patients were randomly allocated (1:1:1:1) to one of the four following study groups: four cycles of standard-interval intravenous EC (epirubicin 90 mg/mBetween April 24, 2003, and July 3, 2006, 2091 patients were randomly assigned to treatment: 545 to q3EC-P, 544 to q3FEC-P, 502 to q2EC-P, and 500 to q2FEC-P. 88 patients were enrolled in centres providing only standard interval schedule and were assigned only to q3FEC-P and q3EC-P; thus, 2091 patients were included in the intention-to-treat analysis for the comparison of EC-P (1047 patients) versus FEC-P (1044 patients) and 2003 patients were included in the intention-to-treat analysis for the comparison of dose-dense (1002 patients) versus standard interval analysis (1001 patients). After a median follow-up of 15·1 years (IQR 8·4-16·3), median disease-free survival was not significantly different between FEC-P and EC-P groups (17·09 years [95% CI 15·51-not reached] vs not reached [17·54-not reached]; unadjusted hazard ratio 1·12 [95% CI 0·98-1·29]; log-rank p=0·11). Median disease-free survival was significantly higher in the dose-dense interval group than the standard-interval group (not reached [95% CI 17·45-not reached] vs 16·52 [14·24-17·54]; 0·77 [95% CI 0·67-0·89]; p=0·0004). The most common grade 3-4 adverse events were neutropenia (200 [37%] of 536 patients in the q3EC-P group vs 257 [48%] of 533 in the q3FEC-P group vs 50 [10%] of 496 q2EC-P vs 97 [20%] of 492) and alopecia (238 [44%] vs 249 [47%] vs 228 [46%] vs 235 [48%]). During extended follow-up, no further grade 3-4 adverse events or deaths related to toxic-effects were reported. Treatment-related serious adverse events were reported in nine (2%) patients in the q3EC-P group, seven (1%) in the q3FEC-P group, nine (2%) in the q2EC-P group, and nine (2%) in the q2FEC-P group. No treatment-related deaths occurred.Updated results from the GIM2 study support that optimal adjuvant chemotherapy for patients with high-risk early breast cancer should not include fluorouracil and should use a dose-dense schedule.Bristol-Myers Squibb, Pharmacia, Dompè Biotec Italy, Italian Ministry of Health, Fondazione Italiana per la Ricerca sul Cancro, and Alliance Against Cancer.

Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results. Patients and methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged

Purpose Primary graft dysfunction (PGD) is a potentially life-threatening complication that may occur in the immediate postoperative period following heart transplantation. We studied the incidence of PGD, its impact on in-hospital and follow-up outcomes and searched for independent risk factors. Methods During an 18-year period (2002-2020), 508 adult individuals underwent isolated heart transplantation at our institution. Patients were diagnosed with none, mild, moderate or severe PGD according to ISHLT criteria. Risk factors for combined moderate/severe PGD were searched with univariate and multivariate analyses. Survival analysis was performed. Results Among the 508 patients, 38 (7.5%) met the ISHLT criteria for mild PGD, 92 (18.1%) for moderate PGD and 23 (4.5%) for severe PGD. Patients were classified into none/mild PGD (393; 77.4%) and moderate/severe PGD (115; 22.6%) groups. Overall in-hospital mortality was 12.4% (7.8% for none/mild PGD and 28.7% for moderate/severe PGD; P Conclusion Our results confirm that PGD is associated with poor in-hospital outcome. Interestingly, the poor outcome doesn't extend beyond the first month of follow-up, with comparable survival between patients with none/mild PGD and moderate/severe PGD in the short and long-term. We found preoperative mechanical circulatory support and preoperative IABP to be independent risk factors for moderate/severe PGD.

Background Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. Patients and methods After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. Results Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test–retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. Conclusion Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.

Se presenta el caso de un recién nacido con isomerismo auricular derecho, cardiopatía congénita compleja y conexión venosa pulmonar anómala total doble asociada que había sido diagnosticado fiablemente con ecocardiografía Doppler bidimensional en color. Seguimiento clinic en un neonato tratado con prostaglandina desde las 24 h de vida hasta su deceso postoperatorio. La cianosis y el soplo cardíaco que evolucionó a distrés respiratorio conforman el marco clínico de un recién nacido varón sin antecedentes obstétricos relevantes. La ecocardiografía emostró situs indeterminado, hipoplasia severa de ventrículo izquierdo, atresia pulmonar y conducto arterioso permeable. Las venas pulmonares se reunían en un collector posterior a la aurícula única, del que ascendía una vena emisaria vertical que conecta con un saco aneurismático. De éste emergen dos vasos venosos: uno hacia vena innominada y otro que conectaba con el techo auricular. El cateterismo cardíaco confirmó la malformación y el enfermo es remitido a cirugía al sexto día de vida, realizándose anastomosis del colector venoso a la aurícula única, implante de una fístula tipo Blalock-Taussig modificada y el cierre del conducto arterioso; el enfermo falleció en la sala operatoria. La asociación de malformación compleja intracardíaca y conexión venosa pulmonar anómala total obstructiva en el contexto de heterotaxia visceroauricular derecha es letal y pocos son los supervivientes con cirugía correctora neonatal. La ecocardiografía Doppler en color es fiable para el diagnóstico y supone una guía indispensable para dirigir el estudio angiográfico. : W e present a newborn infant with right atrial isomerism, complex congenital heart malformation and anomalous pulmonary venous connection, reliably diagnosed by 2-D Doppler color echocardiography. The infant had no significant obstetric antecedents. The neonatal clinical picture included cyanosis, heart murmur and respiratory distress. The infant was treated with prostaglandin fro m the age of 24 hours until his death after surgery. The 2-D echo Doppler color flow mapping showed findings that suggested right atrial isomerism, severe left ventricular hypoplasia, pulmonary atresia and ductus arteriosus. The pulmonary veins flowed together to a posterior cardiac chamber from which an emissary vertical venous vessel connected with a left superior aneurysmal sack. Two venous channels emerged from this sack: one connecting to the innominate vein and the other to the atrium. The malformations were confirmed by cardiac catheterization. On the sixth day of life, the patient underwent anastomosis between the posterior venous chamber with the atrium, a modified Blalock-Taussig shunt implant, and ductus closure but died during surgery. The association between complex cardiac anomalies and uncommon obstructive total anomalous pulmonary venous connection in the context of right atrial isomerism is lethal and few neonates survive surgical repair.Tw o-dimensional echo color flow Doppler is a reliable diagnostic technique and an indispensable guide in angiography.

The normal fetal flow velocity profile across the atrioventricular valves is characterized by an early peak (E), which is related to preload and to active ventricular muscle relaxation, and a higher late peak (A), which is caused by the atrial contraction and also influenced by ventricular compliance. The purpose of this study was to determine how these two elements of ventricular filling change during gestation in both ventricles. A total of 485 normal fetuses from 17 weeks to term were examined by Doppler echocardiography. We measured E and A peak velocities and E/A ratio for both mitral and tricuspid valves. Simple regression analysis was applied to assess possible correlation between Doppler variables and gestational age. Moreover, E and A peak velocities were compared using paired Student's t-test. With the advance of gestation a significant linear increase in the E wave and E/A ratio was found for both mitral and tricuspid valves. The A wave shows little change throughout pregnancy. We found significantly higher Doppler velocities for the tricuspid valve than for the mitral valve. The relationship between the E/A ratios for the two valves and gestational age diverge slightly, with higher values for the mitral E/A ratio. This study shows that the A wave velocity remains constant throughout gestation, suggesting little or no change in ventricular compliance. The E wave is mainly responsible for the change in E/A ratio for both atrioventricular valves during gestation. These findings suggest progressive enhancement of relaxation and elastic recoil, an increase in preload, or both, throughout gestation, rather than a change in myocardial compliance as an explanation for the observed increase in the E/A ratio.

The toxicity in humans of 2,3,7,8-tetrachlorodibenzo-p-dioxin, a man-made compound and environmental pollutant, is still debated. The industrial accident at Seveso, Italy, in 1976 exposed a large population of both sexes and of all ages to a massive concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Monitoring of soil and measurement of blood samples allowed classification of the exposed population into three categories: A, B and R (high, medium and low exposure, respectively). This article presents data from longitudinal health monitoring of the population, including liver function, immune function, neurological impairment, dermatological effects, reproductive pathology, and mortality.

Compression of the median nerve in the carpal tunnel can be produced by a variety of factors, including fractures, metabolic disturbances, rheumatoid arthritis or anatomical anomalies. When it is not possible to identify a specific cause, the term ”idiopathic carpal tunnel syndrome” is used. Although this disease is very common, its pathophysiology is still unclear. In the past, the presence of a chronic non-specific tenosynovitis around the flexor tendons was postulated but several investigations failed to show any inflammatory reaction in the carpal synovium. In this study, the histology of the flexor tendon sheaths in a group of 50 patients surgically treated for idiopathic carpal tunnel syndrome (ICTS) have been investigated both from the qualitative (histopathology) and quantitative (micrometric evaluation) points of view. Lack of acute or chronic inflammatory cells, connective disorganization, and vascular modifications are the main histological findings which are present in all the specimens, regardless of the patient’s age, the duration of the sensory symptomatology or the severity of the neurological lesion on EMG exam. The carpal synovium in these patients appeared thickened when compared to the specimens obtained from the control group. However, on micrometric evaluation a relationship between synovial thickness and severity of the symptomatology or of the EMG data was not observed. The carpal synovium in ICTS has a consistent histological appearance and is increased in thickness when compared with normal specimens.

Cytochrome P450 (CYP) 1B1 activates polycyclic aromatic hydrocarbons and aryl aromatic hydrocarbons to carcinogens. We describe a competitive reverse transcription-PCR (RT-PCR) assay for the quantification of CYP1B1 mRNA in blood mononuclear cells (BMCs) by simultaneous RT and PCR amplification of cellular RNA with decreasing amounts of an internal standard. The concentration of CYP1B1 mRNA is derived from the ratio between the intensities of the bands corresponding to the amplified products. To reduce the variability of mRNA extraction efficiency, the measured amount of CYP1B1 has been calculated in relation to the β-actin gene products. We measured CYP1B1 expression in the BMCs of 75 human subjects; no significant differences in the CYP1B1:β-actin ratio were detected between women (range, 0.47–4.35; median, 2.0) and men (range, 0.72–3.85; median, 2.09). The analytical imprecision (CV) of duplicates was 14% (n = 25 pairs), and the intraindividual CV for two samples, 1 month apart, was 22% (n = 20). No significant differences were detected in smokers (n = 25; range, 0.77–3.55; median, 2.14) compared with nonsmokers (n = 50; range, 0.47–4.35; median, 2.0). The method has a wide range of linearity, good sensitivity and precision, and is suitable for studies of individual susceptibility as indicated by CYP1B1 expression in BMCs.

A seventh-order phase equiripple continuous time filter implementing pulse shaping and noise filtering for partial response maximum likelihood (PRML) read channel applications is presented. The 7-50 MHz cutoff frequency, amount of boost, and group-delay slope are programmable via 7-b digital-to-analog converters (DAC's). At 50 MHz fc, power consumption is 70 mW and output swing for 1% distortion is more than 500 mVpp. The transconductance capacitance (Gm-C) filter is built in a 0.7-/spl mu/m 10-GHz BiCMOS technology.

Background: The different perception and assessment of chemotherapy-induced peripheral neurotoxicity (CIPN) between healthcare providers and patients has not yet been fully addressed, although these two approaches might eventually lead to inconsistent, possibly conflicting interpretation, especially regarding sensory impairment. Patients and methods: A cohort of 281 subjects with stable CIPN was evaluated with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC v. 2.0) sensory scale, the clinical Total Neuropathy Score (TNSc (c)), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sumscore (mISS) and the European Organization for Research and Treatment of Cancer CIPN specific self-report questionnaire (EORTC QOL-CIPN20). Results: Patients' probability estimates showed that the EORTC QLQ-CIPN20 sensory score was overall more highly related to the NCI-CTC sensory score. However, the vibration perception item of the TNSc had a higher probability to be scored 0 for EORTC QLQ-CIPN20 scores lower than 35, as vibration score 2 for EORTC QLQ-CIPN20 scores between 35 and 50 and as grade 3 or 4 for EORTC QLQ-CIPN20 scores higher than 50. The linear models showed a significant trend between each mISS item and increasing EORTC QLQ-CIPN20 sensory scores. Conclusion: None of the clinical items had a perfect relationship with patients' perception, and most of the discrepancies stood in the intermediate levels of CIPN severity. Our data indicate that to achieve a comprehensive knowledge of CIPN including a reliable assessment of both the severity and the quality of CIPN-related sensory impairment, clinical and PRO measures should be always combined.

Background: Thrombolysis with rt-PA is the only approved pharmacological therapy for acute ischemic stroke presently administrable in a 3-hour window (very recently extended to 4.5 h). After this time, the choice is limited to endovascular treatment and antiplatelet drugs, mainly aspirin (ASA), the efficacy of which in the acute phase of stroke has poorly been evaluated. We compared the efficacy of tirofiban, a GP-IIb/IIIa inhibitor, and ASA, with both drugs being administered within 6 h. Methods: 150 patients were randomly assigned to treatment with tirofiban or ASA, both given for 3 days in a double-blind regimen. Major inclusion criteria were stroke onset within 6 h and a baseline National Institute of Health Stroke Scale (NIHSS) score of 5–25. Outcome variables were the proportion of patients with a NIHSS score reduction of ≧4 points after 72 h, and the proportion of patients with an mRS score of 0–1 at 3 months. Results: The trial, originally planned to enroll 300 patients, was halted after enrollment of 150 patients at interim analysis due to the lack of a trend difference between the 2 treatment groups. Neurological improvement at 72 h was observed in 56% of the patients in each group. At the 3-month follow-up, minimal or absent disability was seen in 45% of the patients in the tirofiban group and 53% in the ASA group; these differences were not statistically significant. Three-month mortality was the same in both groups (10.6%); the rates of symptomatic intracranial hemorrhage were 1% (tirofiban) and 4% (ASA). Conclusion: In spite of the fact that the null hypothesis was not supported by our data, we found results supporting the safety (and potential efficacy) of ASA and tirofiban when used in the first hours of acute ischemic stroke. However, this needs to be confirmed by further studies.

The aim of this study was to present a case of deep vein thrombosis (DVT) and pulmonary embolism (PE) after an intrathecal baclofen bolus test. The study was carried out at a tertiary care rehabilitation center in Italy, and it reports a case of a 65-year-old woman affected by primary lateral sclerosis, with lower limb spasticity, who underwent an intrathecal baclofen bolus trial. After a 100 microg baclofen test, she developed hypotension and oxygen desaturation lasting two days. A Doppler ultrasonography was positive for DVT, and echocardiography confirmed the diagnosis of PE. A Doppler ultrasonography performed before the test was negative. This is the first report in the literature of DVT and PE after an intrathecal baclofen bolus trial. Clinicians and patients should be informed that the intrathecal baclofen bolus trial procedure could be associated with rare but important risks such as DVT and PE, and they should be alert in recognizing potentially life-threatening complications.

Solitary fibrous tumours are rare mesenchymal neoplasms usually arising in the pleura. Extra-pleural locations are uncommon although some cases of head and neck involvement have been reported in the recent literature. In such cases, nose, paranasal cavities and parapharyngeal spaces are the most frequently affected sites. The Authors present a case of a solitary fibrous tumour involving the laterocervical spaces. The histological diagnosis of solitary fibrous tumours gives rise to significant problems since parameters for determining their aggressiveness are still controversial. Immunohistochemical techniques are considered to provide a decisive identification. Follow-up plays a crucial role, as recurrences can occur even after several years. Usually, complete surgical excision is adequate whilst curative and radiochemotherapy may be indicated if complete resection of the tumour mass is impossible.

Field results in implementing Signaling system No.7 (SS7) in preparation for the introduction of intelligent network (IN) services are reported. Besides implementing SS7 for interexchange trunk signaling, Italtel has adapted it for communications with remote units, i.e. remote switching modules and subscriber multiplexers and concentrators. IN implementation in a distributed system is discussed. The distributed architecture of the Linea UT intelligent network is described. >

OBJECTIVE: In the last two decades new drugs that oppose the effects of vascular endothelial growth factor receptor (VEGFR), and thus angiogenesis, have considerably improved treatment of solid tumors. These anti-VEGFR drugs, however, are burdened by several side effects, particularly relevant on heart and vessels. Aim of this study was to analyze the changes in cardiovascular structure and function associated with use of anti-VEGFR drugs. DESIGN AND METHOD: 29 patients (27 affected by renal and 2 by thyroid cancer), received treatment with antiVEGFR drugs. Hemodynamic, non invasive arterial investigation (Pulse Wave velocity -cfPWV-, Augmentation Index-Aix- and Aortic Pressure) and echocardiography with global longitudinal strain (gLS) were performed before starting therapy (T0), after 2 (T1) and 6 weeks (T2). Oncologic outcome was determined by the assessment of the neoplastic lesions at CT scans, according to Response Evaluation Criteria in Solid Tumors Guidelines. RESULTS: A significant increase of both peripheral and central blood pressure (BP) was observed. We documented a significant raise of cfPWV from T0 (9.9 ± 2.5m/sec) to T1 (10.6 ± 2.3m/sec); at T2 cfPWV still increased in patients who continued treatment (10.8 ± 2.3m/sec), while decreased in patients who stopped therapy (9.8 ± 1.9m/sec). At the on-treatment CT scan (available in 22 patients) 12 patients had a stable disease (StD), 5 showed a reduction of the lesions (responders -PR-) and 5 showed a disease progression (PD). PD patients showed a lower cfPWV at T2 than StD-PR patients (cfPWV: 9.3 ± 2.8 Vs 13.3 ± 1.5 m/sec; p value 0.02). Aix at T1 was higher in PD than in StD-PR (Aix: 36 ± 2.8% Vs 24.6 ± 9.2%; p value 0.02). CONCLUSIONS: Anti-VEGFR treatment is associated with a marked increase in both brachial and central BP. Moreover it early induces an aortic reversible stiffening. The evidence that cfPWV and AIx changes are early and sensitive cardio-vascular effects of anti-angiogenic treatment and that disease progression is associated with a concomitant come back to pre-treatment value of cfPWV and a further increase in augmentation index, suggests their possible role on oncologic outcome

This continuous time filter is for the read channel of a disk drive using PRML detection. Similar to channels using peak detection, the filter performs two tasks. First it band limits the signal spectrum to about 1/4 of the bit-rate. This rejects high-frequency noise, increasing the signal-to-noise ratio (SNR). Second it equalizes pulse shape to achieve, in conjunction with an adaptive FIR, the target channel response (EPR4). A seventh order phase-equiripple response is used for linear phase response over a wider frequency range than a Bessel response. The filter cutoff frequency is programmable from 7 to 50 MHz for channel rates to 200 Mb/s and a servo information frequency as low as 5 MHz. In addition, both the amount of high frequency boost and the group delay response can be digitally programmed via two 7 b DACs. The boost at cutoff frequency can be changed from 0 to 13 dB while group delay variation from low to high frequency can be varied by /spl plusmn/30%. The filter is implemented in 0.7 /spl mu/m BiCMOS technology.

A number of controlled studies have recently demonstrated the role of disodium pamidronate in the prevention of skeletal complications in patients with metastatic bone disease due to breast cancer and multiple myeloma. They have also shown that it relieves pain and is well tolerated. The aim of this open prospective study was to evaluate the acceptability of a new schedule of pamidronate infusion and to assess pain, analgesic consumption and the Karnofsky Performance Status (KPS) in patients with metastatic bone pain treated with pamidronate in association or not with chemotherapy, radiotherapy, and hormone therapy. Patients with different types of cancer and at least one painful bone metastasis were treated with two cycles of 60 mg intravenous (iv) pamidronate weekly for three consecutive doses, with a 3-week interval between the two cycles (six infusions over 7 weeks), followed by one infusion every 3 weeks for a total of 24 infusions. Two hundred patients were enrolled in the study, of whom 94 received at least the first six infusions; 25 patients received all 24 infusions. Pamidronate was well tolerated in the majority of the patients both during the first six infusions and during the whole study period. In the patients under study, pain intensity decreased compared with T0sub after the first two infusions (second week of treatment). The mean equivalent daily dose of oral morphine required ranged from 21.5 to 41.5 mg/day and was low and stable during the study. For the patients who remained in the study, the KPS remained around 70 during the whole treatment period and intrasubject analysis showed a substantial stability of the KPS within each subject. A first fracture occurred within 321 days in 25% of the whole population under study. Pamidronate represents a further valid therapy to add to an already consolidated list of therapies such as radiotherapy, chemotherapy, hormone therapy and orthopaedic intervention in the pain management of patients with bone metastases. Future studies are necessary to evaluate the role of pamidronate and the appropriate schedule in patients with advanced or terminal cancer who are no longer being treated with oncological therapies.

We report a preterm infant weighing 1,680-g with critical pulmonary stenosis. Pulmonary balloon valvuloplasty was successfully performed using a = 1.15 balloon/annulus ratio.

The bidirectional Glenn shunt is a well established surgical technique in children with complex congenital heart disease. The present study is a retrospective analysis of patients undergoing this operation in order to assess the influence of different variables in the outcome.From December 1990 to June 2000, 100 patients received a bidirectional Glenn shunt. Two groups were defined, based on the outcome. Group A (n = 15, unsuccessfully result) including death and need to reoperate, and Group B (n = 85, patients with good outcome).The mortality was 8%. Eight patients were reoperated at follow-up. The survivors were followed for a mean of 3.5 years. Mean pulmonary artery pressure 7 mmHg was a factor associated with poor clinical progress. Other variables (age less than 1 year, excessive pulmonary blood flow, double Glenn operation, significant anatomic anomalies, and arrythmias), were also associated with outcome. Significant variations were observed in the time of by-pass or the need for aortic clamp in cases with simultaneous operative repair of pulmonary branch stenosis. Actuarial survival rate, most more than 1 year was 92%, and freedom from reoperation at 3 years was 90%.The bidirectional Glenn shunt is an excellent palliation in patients with functionally single ventricle. Mean pulmonary artery pressure was the most important variable related with the outcome. We are encouraged to continue with tendency to perform bidirectional Glenn shunt preferably early, avoiding, whenever possible, previous palliative surgery.

We present a newborn infant with right atrial isomerism, complex congenital heart malformation and anomalous pulmonary venous connection, reliably diagnosed by 2-D Doppler color echocardiography. The infant had no significant obstetric antecedents. The neonatal clinical picture included cyanosis, heart murmur and respiratory distress. The infant was treated with prostaglandin from the age of 24 hours until his death after surgery. The 2-D echo Doppler color flow mapping showed findings that suggested right atrial isomerism, severe left ventricular hypoplasia, pulmonary atresia and ductus arteriosus. The pulmonary veins flowed together to a posterior cardiac chamber from which an emissary vertical venous vessel connected with a left superior aneurysmal sack. Two venous channels emerged from this sack: one connecting to the innominate vein and the other to the atrium. The malformations were confirmed by cardiac catheterization. On the sixth day of life, the patient underwent anastomosis between the posterior venous chamber with the atrium, a modified Blalock-Taussig shunt implant, and ductus closure but died during surgery. The association between complex cardiac anomalies and uncommon obstructive total anomalous pulmonary venous connection in the context of right atrial isomerism is lethal and few neonates survive surgical repair. Two-dimensional echo color flow Doppler is a reliable diagnostic technique and an indispensable guide in angiography.

A divided left atrium because of cor triatriatum is a relatively rare cardiac anomaly requiring corrective surgery. We describe here our clinical and surgical experience with this congenital heart defect as well as the different medium and long term diagnostic, surgical and evolution aspects.From 1981 to 1999, 15 children with cor triatriatum without complex associated cardiovascular defects underwent surgery at a mean age of 13 months (excision of the obstructive membrane). The surgical reports were reviewed and the clinical and echocardiographic data were analyzed before and after the intervention; six of these patients (40%) were referred to operating room only with the 2-D echo Doppler technique and color flow mapping information. The follow-up period ranged from 8 months to 19.3 years.Diagnosis was confirmed during the surgical procedure. One 9 month old patient died 60 days after a successful corrective surgery because of sepsis (7%). No late deaths or reoperations were found in the follow-up period. All 14 patients who survived the operation have a functional class I (NYHA), and they are asymptomatic in the follow-up. The overall survival rate was 93% (70% CI: 87-90).Corrective surgery with excision of the obstructive membrane dividing the left atrium restores normal anatomic, hemodynamic and clinical status in children with cor triatriatum without complex associated defects.

The compound, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is produced as an unwanted by-product of various chemical reactions and combustion processes, including the manufacture of chlorinated phenols and derivatives. In animals, TCDD exposure is associated with toxic, carcinogenic, developmental, and reproductive effects. In 1976, a chemical plant explosion in Seveso, Italy, exposed the residents in the surrounding community to the highest exposure to TCDD known in humans. Materials from an aerosol cloud of sodium hydroxide, sodium trichlorophenate and TCDD were deposited over an 18.1 km2 area. As evidence of the significant level of TCDD exposure, numerous animals died and 193 cases of chloracne were reported among residents of the area. Initially, the contaminated area was divided into three major exposure Zones (A, B, R) based on the concentration of TCDD in surface soils. To date, the majority of epidemiologic studies conducted in Seveso have used Zone of residence as a proxy measure of exposure. The purpose of the present study is to validate the use of Zone of residence in Seveso as a proxy measure of exposure against individual serum TCDD measurement, and to determine whether questionnaire information can improve the accuracy of the exposure classification. Using data collected from the Seveso Women's Health Study (SWHS), the first comprehensive epidemiologic study of the reproductive health of women in Seveso, we determined that Zone of residence is a good predictor of individual serum TCDD level, explaining 24% of the variance. Using questionnaire information could have improved prediction of individual exposure levels in Seveso, increasing the percent of the variation in serum TCDD levels explained to 42%.

This report describes the unusual association between the interruption of the aortic arch type B and aortopulmonary window type II in a neonate. When the patient was 20 days old, a one-stage surgical repair was done through left side thoracotomy without circulatory by-pass, making a left carotid artery to descending aorta anastomosis, closing the window with a hemaclip, respectively. A routine 2-D Doppler color echocardiography performed in the immediate postoperative period showed the absence of blood flow in the right pulmonary artery. The patient required a new intervention, changing the position of the clip in order to restore the normal pulmonary blood flow. Eight months after surgery, the "neoaortic arch" grows in harmony with the body surface area, without signs of cerebral circulatory deficiency or significant gradient at any level.

To analyze the efficacy of balloon pulmonary valvuloplasty (BPV) as the elective treatment for neonatal critical pulmonary valvar stenosis (PVS).The results of clinical and echocardiographic features before and after the BPV were reviewed in 29 neonates (18+/-12 days of life). Different hemodynamic and 2-D color Doppler echocardiographic were evaluated. The BPV result was classified as favourable if no other balloon or surgical therapy was required to normalise pulmonary flow and achieve a sustained right ventricle-pulmonary artery (RV-PA) Doppler gradient below 40 mmHg. It was considered unfavourable if the neonate died, needed surgery or redilation and/or the RV-PA Doppler gradient wasor =40 mm Hg. The study developed in three phases: pre BPV immediate post BPV until the hospital discharge (14+/-11 days), and in the mid-term follow-up of between 8 and 96 months (51+/-31 months).Mortality was not registered with BPV. The RV/left ventricular systolic pressure decreased from 1.4+/-0.3 to 0.8+/-0.3 (p0.01) as a consequence of the dilation, and the the systemic oxygen saturation increased from 85 +/-12 to 92+/-6% (p0.01). The RV-PA Doppler gradient diminished from 86+/-18 to 28+/-16 mm Hg immediately after BPV (p0.01) and was registered at 13+/-6 mm Hg in the follow-up (n = 24). The RV-PA junction Z value grew from -1.25+/-0.9 before valvuloplasty to -0.51 +/-0.7 at the final echocardiogram (p0.01). No changes in the tricuspid diameter were detected between both periods of time. Five neonates obtained unsatisfactory results: 4 in the immediate post BPV (systemic-pulmonary artery shunt 2, transannular patch 2), and 1 in the mid-term follow-up (valvectomy + transannular patch). The actuarial curve reflects that 82,7% of the patients were free form reinterventions at 8 years.BPV is safe and effective to relief PVS in the neonate. The balloon promotes advantageous changes in both, pulmonary annulus and the right ventricle. In addition, the RV-PA Doppler gradient observations in the follow-up, support the expectation that the BPV is a "curative" therapy.

A two-month old infant is described with the rare combination of absent pulmonary valve syndrome, ventricular septal defect, pulmonar "anular" stenosis and ductal origin of the left pulmonary artery. The diagnosis that was confirmed in the operating room was made by 2-D echocardiographic Doppler color flow mapping study without the support of cardiac catheterization.

The aim of this work is to describe the different aspects of diagnosis and postoperative follow-up in four patients after surgery for aortic-left ventricular tunnel (ALVT). The surgical techniques and results have been published, in the literature but there are no reports about the progression of aortic regurgitation.We reviewed the clinical features of four patients operated with ALVT. The clinical information (electrocar-diograms, echocardiograms and catheterilution) was studied in the preoperative period. Surgical technique and postoperative evolution were analysed. The follow-up period ranged between 4.7 and 13 years.In a 14 years period, four children (2 boys and 2 girls), were operated for ALVT. The mean age at the time of diagnosis was 8.5 years (ranged between 1 month and 14 years). A continuous murmurs was present in all cases, associated to cardiac failure in the youngest patient (1 month old). The clinical diagnosis was ALVT in the four cases but only in two the echocardiographic study showed correctly the anatomic aspects of the malformation. The angiohemodynamic study was correct in three patients and the differential diagnosis was made in last one with rupture of aortic sinuses of Valsalva to the left ventricle. All cases were operated; with direct closure of the aortic orifice (two cases), or with dacron patch (two cases). In one case aortic valve replacement was also performed. There was not mortality and the mean age at the time of surgery was 9 years (1.5 months and 14 years). The mean follow-up was 8.5 years (ranged between 4.7 and 13 years), three patients showed clinically and in the echocardiogram study an aortic valvular regurgitation without ALVT deshiscence. All cases are asymptomatic. No patient was reoperated.The surgical treatment of ALVT must be done as soon as the diagnosis is made to prevent left ventricular enlargement, ventriculo-aortic floor distortion and aortic valvular lesion. A precise echocardiographic study is necessary to avoid catheterization. This study provided a clear knowledge of anatomic structure of the ALVT for both clinician and surgeons. This information is important in order to obtain an optimal surgical success, particularly to prevent the valvar aortic regurgitation.

In 1976 the population of an area including Seveso (about 30,000) affected by the fallout of a toxic cloud containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) started a health monitoring plan which lasted until 1985. Smaller groups were monitored until 1997. The large number of people and the different toxic effects on organs have gathered different discipline experts including informatic. This work has permitted the not easy observation both of minor and bigger effects during two decades.

We report a neonate with distal bilateral ductus arteriosus origin of nonconfluent pulmonary arteries which was only diagnosed accurately by 2-D echo Doppler color flow mapping in the context of situs ambiguous, univentricular A-V connection and pulmonary atresia with normal systemic/pulmonary venous drainage. The color flow appearance of this singular vascular anatomy was enhanced after prostaglandin administration, which, allowed us to see an image resembling a "moustache morphology". At 36 months of age, and after a successful bilateral 4 mm modified Blalock Taussig shunt implantation by sequential approach, the patient is waiting for the next surgical step which will include a restoration of the confluence of the pulmonary arteries with bidirectional Glenn operation. Brief embryological and differential diagnosis comments are discussed.

The selection of patients for balloon aortic valvuloplasty is a vital clinical challenge in neonatal aortic stenosis. The present study was designed to establish possible predicting factors for poor results after balloon therapy.2D echocardiographic, Doppler color and clinical variables (grade of cardiac failure, aortic "anulus", mitral anulus, left ventricular diameter, ascending aorta, instantaneous Doppler gradient, and grade of aortic regurgitation) were analyzed in 32 neonates submitted to balloon dilation at 22 +/- 18 days of life. The evaluations were conducted during three periods in respect to balloon therapy (A: before; B: immediately after, and C: mid-term follow-up). The outcome in both, B and C periods was defined as favorable (all survivors with Doppler gradientor = 70 mmHg and no other intervention on the valve) and unfavorable (death, first stage of univentricularization, valvular replacement or survivors with Doppler gradient70 mmHg). Mean values between subgroups were compared by Wilcoxon test; unconditional logistic regression was used to analyze the impact of cardiac failure and anatomic variables (continuous, categorized or Z) on the outcome.The Doppler gradient decreased from 70 +/- 28 to 34 +/- 14 mmHg after the valvuloplasty, and no changes were detected in the follow-up period (36 +/- 8 mmHg). An immediate favorable result was obtained in 72% of the patients; its consisted of 50% in period C. Nine neonates had an immediate unfavorable outcome (6 deaths and 3 with Norwood operation). In the follow-up, three patients had valvular replacement, one patient Doppler gradient70 mmHg and one patient with left ventricular endomyocardial abnormalities died. The severe cardiac failure (odds ratio: 33; CL 2.4-443; p = 0.008) and all categorized anatomic variables (aortic "anulus"or = 6 mm; mitral anulusor = 9 mm; ascending aortaor = 8 mm; left ventricular diameteror = 13 mm) were related with the immediate poor outcome. At 7.6 years, survival and freedom with no valvular replacement nor reintervention probability rates were 83% and 67%, respectively.2D echo Doppler provides essential information about the anatomic and functional lesions coexisting with severe or critical aortic stenosis in neonates. Patients with left heart hypoplasia and severe heart failure should not be candidates for balloon valvuloplasty. The degree of residual aortic regurgitation and endomyocardial abnormalities of the left ventricle play an important role in the mid-term follow-up.

Deep vein thrombosis incidence is 1/1000 per year; it is associated with many risk factors which is considered as "thrombophilic states". Its pathogenesis is complex, caused by alterations of hemostasis system. Many studies have established the relation between cancer and subsequent venous thromboembolism, confirming the relationship of neoplastic cell interaction with coagulation system. Forty-seven patients admitted to the hospital from 1987 to 1996 with symptomatic clinically proved deep vein thrombosis were included in a retrospective study. Routine examination at the time of diagnosis of deep vein thrombosis revealed an occult cancer in 8 out of 47 patients; 9 out of 47 patients were admitted in hospital with vein thrombosis and known cancer. The aim of this study is to suggest the best, first treatment of vein thromboembolism in emergency to avoid the dangerous pulmonary embolism complication. The patients affected with deep vein thrombosis and cancer were elderly (over 70 years old, in mean); the neoplasia was of digestive system (8/17) in advanced metastatic stage there was cancer familiarity in 7 out of 47 patients. The high risk of pulmonary embolism associated to deep vein thrombosis suggests the importance of early starting the anticoagulant therapy and placing caval filter.

To evaluate the prevalence, the incidence and the history of cholelithiasis in liver cirrhosis.A series of 233 consecutive cirrhotic patients (193 Child A, 35 Child B and 5 Child C) were assessed for cholelithiasis by ultrasonography. Of these, 201 (those who had never had cholecystectomy) were followed-up with repeated ultrasonographies.The prevalence of cholelithiasis was 38% (22% gallstones and 16% previous cholecystectomies). No relationships with the usual risk factors for cholesterol gallstones, such as age, sex, body mass index, serum glucose or triglycerides, were found. On the contrary, close correlations were observed with serum albumin, bilirubin, prothrombin time and Pugh score. By multivariate analysis, only serum bilirubin was independently correlated with cholelithiasis. Histories of biliary pain were more frequent in patients with previous cholecystectomy (62% cases) than in those with gallstones (21%) and those without cholelithiasis (7%). On the contrary, complaints of dyspepsia were similar in the three groups of patients. During a mean follow-up of 34.4 +/- 0.9 months, there was a 4.9% annual rate of development of new stones in 127 patients without cholelithiasis at the first investigation. This rate is markedly higher than that reported for normal subjects in a previous survey carried out in a similar geographic area. During a mean follow-up of 31.8 +/- 1.2 months, symptoms or complications were seen in 2 out of 45 patients with initial gallstones (4.4%). The annual rate of complications was estimated to be less than 2%.Cholelithiasis is frequently associated with cirrhosis and the risk of developing new stones remains high during the natural history of the disease.

Diarrhea is one of the dose-limiting toxicities for administration of fluorouracil (5FU) in patients with colorectal cancer and can result in severe morbidity and mortality. No well-defined prognostic factors influencing 5FU-associated diarrhea have been identified, which means its occurrence is unforeseeable. The aim of this study was to check whether any characteristics related to patients or chemotherapy could allow the identification of subsets of patients at higher risk of developing diarrhea while receiving a regimen containing 5FU. A logistic regression analysis was performed with age, sex, site of primary tumor, presence of primary tumor, presence of colostomy, time since surgery, number of courses of chemotherapy, diarrhea in previous courses, season of treatment, and chemotherapeutic regimens used as model parameters to predict occurrence of diarrhea in 258 colorectal cancer patients receiving a 5FU-containing regimen. Presence of primary tumor (P = 0.004), previous episodes of chemotherapy-related diarrhea (P = 0.00005) and summer season (P = 0.014) were found to be significant risk factors for developing diarrhea. The other variables examined, such as age, sex, chemotherapeutic regimen, site of primary tumor, presence of colostomy, and time since surgery, were not significantly correlated to diarrhea. Chemotherapeutic regimen was the only parameter that allowed prediction of the severity of diarrhea: 5FU/6S-leucovorin/interferon caused more severe diarrhea, followed by 5FU/leucovorin weekly. Although the analysis of these clinical features does not seem to allow the definition of a well-defined subset of colorectal cancer patients at higher risk of 5FU-induced diarrhea, it can be recommended that patients with primary tumor, or who have experienced diarrhea in earlier courses of chemotherapy or are receiving treatment in summer should be carefully monitored, especially in the first cycles.

Several clinical studies have demonstrated the efficacy of subcutaneous immunotherapy with Il-2 alone in metastatic renal cell carcinoma (RCC). In an attempt to better define the clinical parameters which may predict the efficacy of treatment, the present study shows the results obtained with subcutaneous Il-2 alone in 91 evaluable metastatic RCC patients. IL-2 was injected subcutaneously at 3 million IU twice/day for 5 days/week for 6 weeks, corresponding to one immunotherapeutic cycle. In nonprogressing patients, a second cycle was given after 28-day rest period. A complete response (CR) was achieved in 2/91 patients. Moreover, 19/91 patients had a partial response (PR). Therefore, objective response (OR) rate was 21/91 (23%) patients. Stable disease (SD) was achieved in 41 patients, while the remaining 29 patients had a progressive disease (PD). OR rate was significantly higher in patients with a long disease-free survival than in patients with synchronous metastases, in nephrectomized patients than in the non-nephrectomized ones, and in patients with high than in those with low PS. The survival obtained in patients with CR or PA was significantly longer with respect to that found in patients with SD or PD. The toxicity was substantially low in all patients. This study confirms that the subcutaneous immunotherapy with IL-2 alone is an effective and well tolerated therapy of metastatic RCC.

Variceal bleeding and hepatocellular carcinoma are two severe complications of cirrhosis. One of our patients who bled from oesophageal varices was found to have a malignant hepatic nodule. As the patient refused liver transplantation, a transjugular intrahepatic portosystemic stent was carried out for portal hypertension, and transcatheter arterial chemoembolization for cancer. Both procedures were successful and one year later liver function has not deteriorated. This case shows that intrahepatic stent placement and selective arterial chemoembolization can be safely performed in cirrhotic patients with a solitary hepatocarcinoma nodule and a good liver function reserve.

Fetal cardiac growth was studied by two-dimensional echocardiography. The size of various cardiac structures were compared with gestational age. Normal values for each measurement were determined, with special attention being paid to the differences between the right and left chambers.Ninety human fetuses with a gestational ages between 17 and 39 weeks were studied. Any structural abnormality was excluded at prenatal and postnatal examination. Aortic, pulmonary artery, tricuspid and mitral valve annulus diameters were measured with classical echocardiographic views. These variables were compared between them and plotted against gestational age. The correlations were determined by Student's T-test and regression analysis using 95% confidence limits.A good correlation (r0,7) between all the measurements and gestational age was obtained. In absolute values, tricuspid and pulmonary artery valve diameters were significantly greater (p0,01) than mitral and aortic valve diameters, respectively. Nevertheless, the diastolic diameter of the left ventricle (LV) was slightly greater than the diastolic diameter of the right ventricle (RV). Separating the data of the second trimester from of those of the third, the initial dominance of LV (RV/LV ratio = 0,93) tends to disappear and a slight dominance of RV (RV/LV ratio = 1,03) was observed at term.This study establishes normal values based on two-dimensional echocardiographic cardiac measurements throughout gestational stages. The data obtained will be very useful for the prenatal diagnosis and perinatal management of certain cardiopathies like the hypoplastic left heart syndrome. The relative dominance of RV in utero was also demonstrated. The different morphology of both ventricular outflow tracts and their volume changes throughout gestation, secondary to placental resistance variation, could justify the changes in the RV/LV ratio during the intrauterine period.

Aneurysm of the atrial septum at the level of the foramen ovale is reported commonly at the routine fetal echocardiographic examination. Cases with entire involvement of the atrial septum have been exceptionally reported. We described the data concerning the prenatal detection of a total redundancy of the atrial septum in 6 cases without congenital heart disease.The gestational age was between 28 and 38 weeks, and none of the fetuses had evidence of heart defect. A routine fetal echocardiography was made in all the cases. Rhythm disturbances were studied by M mode. During the first three months of life, a cardiologic control was made in all the cases.The large displacement of the atrial septum towards the left atrium was clearly visualized in four-chambers view; by using Pulsed Doppler and Color flow mapping, the pulmonary venous return and mitral orifice flow were not impaired. Premature atrial beats were found in two fetuses and no hemodynamic disfunction was observed in all entire study group. Postnatal echocardiographic control was normal in all patients. The atrial septum becomes completely rectified with normal patency of the foramen ovale membrane in the newborn studies. The supraventricular extrasystoles were confirmed in the neonatal period. In both, the arrhythmia disappeared in a few days after delivery without treatment.Despite the benign follow-up in our cases, the unexpected presence of an extremely redundant atrial septum, leads to a close prenatal attention particularly in the presence of rhythm disturbance. The pathologic substrate of this anomaly might be an intrinsic alteration of the myocardial structure of the septum like seems demonstrated in the aneurysm circumscribed to area of the fossa ovalis [correction of fosa ovale]. The increase in the left atrial pressure after birth will produce a normal 2-D echo patterns in the newborn period.