Interventional Catheterization after Total Cavopulmonary Connection: Experience in 68 Patients

Background: Total cavopulmonary connection (TCPC) is performed in patients having a single ventricle to allow the passive flow of systemic venous blood to the lungs. Interventional catheterization is needed to treat residual defects or complications. Aims: We discuss our results concerning 68 patients who had had TCPC from January 1995 to December 2010. Methods: Initial and follow‐up catheterization data were reviewed retrospectively. Mid ‐ term results were evaluated by means of angiography and/or CT scan. Results: Mean age at TCPC was 5 years (2.5–18); mean interval between TCPC and catheterization was 5.6 years (1.5–15). Sixty‐nine catheterizations were performed in 53 patients. Eleven patients (21%) had low venous pressure, did not display a right‐to‐left shunt, and did not need any intervention. Fifteen patients (28%) had low venous pressure and only needed the closure of the fenestration. The remaining 27 patients (51%) needed the following interventions: embolization of venous vessels prompting right‐to‐left shunt (n = 15), stenting or reconnection of pulmonary arteries (n = 5), stenting or recanalization of systemic veins (n = 11), other procedures (n = 5). In 3 patients the fenestration could not be closed due to high venous pressure. After the interventions oxygen saturation increased from 90.5%± 4.8% to 94.7%± 3.6% (P = 0.002). Conclusions: Our data show that 49% of patients with TCPC are in good condition late after surgery. However, half of these patients continue to need interventions generally aimed at suppressing stenoses at various levels of TCPC or at occluding vessels prompting right‐to‐left shunt. This population should enter a multicenter program aimed at identifying patients at risk. (J Interven Cardiol 2012;25:622–627)     

Carcinoma of the breast metastatic to the ureter seven years later

We present a case of ureteral metastasis from a primary breast cancer where the disease recurred with an episode of renal colic 7 years after diagnosis. A surgical operation was performed to remove the terminal ureter and the perimeatal area of the urinary bladder. Urological and radiological outcome was satisfactory after a 2-year follow up.     

Different Trends of Changes in Heart Rate Variability in Patients with Anterior and Inferior Acute Myocardial Infarction

Modifications in heart rate variability (HRV) parameters occur after acute myocardial infarction. The aim of this study was to evaluate the trend of HRV change during the acute phase and the first month after myocardial infarction, and establish whether they were affected by the anterior or inferior location of the infarction. The time-domain HRV measures of 59 patients with a first uncomplicated acute myocardial infarction were computed from 24-hour ECG recordings made on days 1, 2, 10, and 28 after hospital admission. At day 1, the mean RR cycle length (NN), the standard deviation of the NN intervals (SDNN), and the root mean square successive difference of NN intervals (RMSSD) were lower in the patients with anterior myocardial infarction. Although the parameters were similar in all of the patients at day 28, their behavior over time was different (P = 0.01): the SDNN in the patients with inferior myocardial infarction had decreased to the values found in anterior myocardial infarction patients by day 2 but, at day 10, both NN and SDNN tended to recover in both groups; RMSSD had diminished in both groups by day 2, but at day 10, had increased in the patients with anterior, but not in those with inferior myocardial infarction. These findings suggest that (1) in the very early phase of myocardial infarction, HRV is different in the two locations, (2) during the first hours of myocardial infarction patients with inferior location showed a greater vagal activity than patients with anterior location that became lower at day 10, and (3) the recovery of HRV is an early phenomenon in both groups, being already evident by the second week after myocardial infarction.     

Electroanatomic Mapping and Ablation of Macroreentrant Atrial Tachycardia: Comparison Between Successfully and Unsuccessfully Treated Cases

Ablation of Macroreentrant Atrial Tachycardia. Introduction: Ablation of macroreentrant atrial tachycardia (MRAT) is demanding and identification of predictors of failure may be of help in patient management. This study compares the characteristics of successfully versus unsuccessfully treated patients undergoing electroanatomic mapping (EAM) and ablation of MRAT. Methods and Results: Consecutive patients undergoing EAM and ablation of MRAT were included. Ablation was linearly placed at the mid‐diastolic isthmus (MDI) to achieve arrhythmia interruption and conduction block. Variables were analyzed for predictors of both procedural failure and cumulative failure (procedural failure + early recurrences). Fifty‐two patients (37 M; age 64 ± 16 years) with 56 MRATs were considered. The MRAT was in the right atrium in 25 morphologies (45%) and 32 (57%) showed a double‐loop reentry. Fifty‐one morphologies (91%) in 47 patients were successfully treated; 3 patients had early recurrences of the same MRAT. None of the clinical variables considered significantly differed in the successfully treated group as compared to the unsuccessfully treated. Conversely, there was a significant difference as to the EAM characteristics: successfully treated cases showed a narrower target isthmus with a lower voltage amplitude and slower conduction velocity (CV). In the MDI, a CV >60 cm/sec and a width >40 mm were the strongest predictors of procedural failure and cumulative failure, respectively. Conclusions: In this patient population, while the clinical variables did not differ significantly, there was a significant difference in the EAM characteristics between successfully and unsuccessfully treated cases. CV and width of the isthmus target for ablation were the strongest independent predictors of procedure outcome. (J Cardiovasc Electrophysiol, Vol. 21, pp. 155‐162, February 2010)     

p53 OVEREXPRESSION AND HUMAN PAPILLOMAVIRUS INFECTION IN TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER: CORRELATION WITH HISTOLOGICAL PARAMETERS

Seventy-nine transitional cell carcinomas (TCCs) of the urinary bladder (25 grade 1, 22 grade 2, and 32 grade 3 tumours) were examined for p53 overexpression by immunohistochemistry with a monoclonal antibody and for human papillomavirus (HPV) infection by the polymerase chain reaction (PCR). Positive immunostaining for p53 was detected in 40·5 per cent of the cases; the percentage of positive cases was significantly lower in low-grade (G1 and G2) TCCs than in high-grade (G3) tumours (10·6 per cent vs. 84·4 per cent; P <0·0001). The overall rate of HPV infection was 32·9 per cent; 20·3 per cent of the cases were positive for HPV 16, 3·8 per cent for HPV 18, and 8·9 per cent for both. Consensus primers as well as type-specific primers for HPV types 6, 11, and 33 failed to detect any additional case with HPV infection. The prevalence of HPV 16 and/or HPV 18 infection was significantly higher in low-grade than in high-grade tumours (44·7 per cent vs. 15·6 per cent; P =0·0061). p53-positive cases were more common among papillary, deeply infiltrating tumours, and HPV-positive cases among papillary, non-infiltrating lesions. According to these data, p53 overexpression and HPV 16/18 infection are common findings in bladder TCC and there appears to be an inverse correlation of p53 overexpression and of HPV infection with tumour aggressiveness. The possibility of different molecular pathways in superficial low-grade and in invasive high-grade tumours is suggested.     

Unexpected Immunoresponse to Gal and APA Antigens in Diabetic Type 1 Patients Receiving Neonatal Pig Islets After 6 Years

Cotransplantation of porcine islets and Sertoli cells into preimplanted subcutaneous devices improve metabolic control in type 1 diabetic patients, and survive grafted for more than 4 years. We report here, further assessment of the endocrine and porcine nature of the surviving cells and the immune responses elicited toward Gal α(1,3)-Gal β(1,4)-GlcNAc (Gal) antigen in patients who received a second and third transplants. No immunosuppressive drugs were administered. We were able to immunostain insulin- and glucagon-positive cells in all biopsies of patients and Sertoli cell markers in 60.9% of biopsies. Additionally, all biopsies tested, amplified the porcine COII gene. Patients demonstrated an increase in antipig antibodies in response to the first transplant with a decreasing response toward the second and third transplants. In all transplants, the IgG levels promptly returned to basal values after 3–4 months. The long-term survival of porcine cells and the reduced humoral immune response to multiple transplants indicate a form of tolerance. We have not been able to find CD25-positive cells, indicating that it is probably an immune accommodation of the graft.     

Malignancy: Changes in Circulating Immature and Mature Dendritic Cells During IL-2 Cancer Immunotherapy and Their Relation with Lymphocyte Increase and Clinical Response

Lymphocytosis is the main biomarker predicting the efficacy of subcutaneous IL-2 anticancer immunotherapy. In addition, it has been demonstrated the fundamental role of dendritic cells (DC) in the generation of an effective anticancer immunity. However, the relation between IL-2 and DC system needs to be further understood. This preliminary study was performed in an attempt to analyze changes in circulating DC during IL-2 cancer immunotherapy in relation to lymphocyte variations and clinical efficacy of treatment. The study included 20 metastatic renal cell cancer patients, who underwent subcutaneous low-dose IL-2 immunotherapy (6.000.000 IU/day for 6 days/week for 4 weeks). To evaluate DC, venous blood samples were collected before and after 2 weeks of IL-2 injections, corresponding to the period of maximum lymphocytosis. Immature (CD123(+) ) and mature (CD11c(+) ) DC were measured by FACS and monoclonal antibodies. IL-2 induced a significant increase in the mean number of circulating mature DC, whereas no substantial change occurred in immature DC mean number. The increase in mature DC was associated with a control of disease, whereas no rise was observed in patients who had progressed on IL-2 immunotherapy. Moreover, the increase in mature DC mean number was significantly higher in patients showing evident lymphocytosis, with lymphocyte enhancement greater than 1000 cells/mmc, than in patients with less pronounced lymphocytosis, even though no significant correlation was seen in between mature DC and lymphocyte increase. This preliminary study would suggest that IL-2 may stimulate DC system and that the clinical anticancer efficacy of IL-2 is associated with the increase in circulating mature DC, which could be considered as a new favourable biomarker during IL-2 immunotherapy.     

Allogeneic bone marrow transplantation versus chemotherapy in high-risk childhood acute lymphoblastic leukaemia in first remission

We compared the outcome of children with high-risk acute lymphoblastic leukaemia (HR-ALL) in first complete remission (first CR) treated with chemotherapy (CHEMO) or with allogeneic bone marrow transplantation (BMT) in a multicentre study.   All children treated by the Italian Paediatric Haematology Oncology Association for HR-ALL in first CR between 1986 and 1994 were eligible for the study. 30 children were given BMT at a median of 4 months from first CR, with preparative regimens including total-body irradiation ( n  =25/30). 130 matched controls for BMT patients were identified among 397 HR-ALL CHEMO patients. Matching on main prognostic factors and duration of first CR was adopted to control the selection and time-to-transplant biases. The comparative analysis was based on the results of a stratified Cox model. The estimated hazard ratios of BMT versus CHEMO at 6 months, 1 year and 2 years after CR were 1.38 (CI 0.59–3.24), 0.69 (CI 0.27–1.77) and 0.35 (CI 0.06–1{\raise 5mu ..91), with an overall non-significant difference between the two groups ( P  = 0.34). With a median follow-up of 4 years, the disease-free survival was 58.5% (SE 9.3) in the BMT group and 47.7% (SE 4.8) in the CHEMO group, at 4 years from CR. Non-leukaemic death occurred in 4% of CHEMO and 10% of BMT patients. In the BMT group the estimated cumulative incidence of relapse at 1.5 years from CR was 31.5% (SE 8.8) and did not change thereafter, whereas in the CHEMO group the corresponding figure was 29.2% (SE 4.1) and the incidence continued to increase thereafter (48.2% (SE 4.8) at 4 years from CR).   The results of this study suggest that, with respect to the CHEMO group, the higher risk of early failure in the BMT group is outweighed by the lower risk of relapse after 1 year. Results prompt the need for a prospective study, in order to demonstrate the likely advantage of BMT in HR childhood ALL in first CR.     

Synthesis of TPH-13, a new tridecapeptide from Phyllomedusa rohdei

The synthesis of TPH-13 (Glp-Glu-Lys-Pro-Tyr-Trp-Pro-Pro-Pro-Ile-Tyr-Pro-Met-OH), a tridecapeptide isolated from the skin of the South American frog Phyllomedusa rohdei, is described and alternative approaches are discussed.     

Dehydro-dermorphins

Dehydrophenylalanine having the Z-configuration (ΔPhe) and D-Phe were incorporated in positions 3 and/or 5 into dermorphin-(1–5)-peptide amide (H-Tyr-D-Ala-Phe-Gly-Tyr-NH₂) in order to study the effect of structure or configurational changes. On GPI preparation, whereas the activity of [L-Phe⁵]-pentapeptide was fourfold higher than parent peptide and comparable to that of dermorphin, the substitution of Phe³ by its D-enantiomer was barely tolerated. The pentapeptides containing ΔPhe in positions 3 and/or 5 displayed even lower potency: particularly the unsaturation at position 3 alone or at position 3 and 5 was very detrimental to μ activity.