Surgery for right ventricle to pulmonary artery conduit obstruction: risk factors for further reoperation.

OBJECTIVE: To identify the surgical approaches and risk factors which influence longevity of right ventricle to pulmonary artery (RV-PA) conduits following first reoperation for obstruction. METHODS: Between January 1993 and August 2003, 114 patients underwent 141 reoperations for RV-PA conduit obstruction. Diagnoses included 'Truncus Arteriosus' (n=52), 'Pulmonary atresia/Tetralogy of fallot' (n=39), 'Double outlet right ventricle' (n=10), 'Transposition of great arteries, VSD, and pulmonary atresia' (n=9), and the 'Ross operation' (n=4). All patients had undergone a previous biventricular repair. The first reoperation for conduit obstruction was performed in 112 hospital survivors by: total conduit replacement (Group A, n=73) with valved (homograft=10 and xenograft=54) or non-valved (n=9) conduit, and patch enlargement of the obstructed RV outflow tract with preservation of the posterior and sides of the conduit wall after removing of the fibrocalcific peel and degenerated valve (Group B, n=39). Mean age at first reoperation was 8.8+/-6.7 and 7.5+/-5.3 years in patients of groups A and B, respectively. Seven patients in Group A and 18 in Group B required a second reoperation and two patients in Group B a third reoperation. RESULTS: There were two hospital deaths and no late deaths. Mean follow-up was 5.8+/-3.2 years. Risk factors for second reoperation by univariate analysis were: homograft conduit use (P=0.004), Group B surgical approach (P=0.0001), higher RV-PA systolic pressure gradient at discharge (P=0.02), and age <5-years-old (P=0.01). Multivariate analysis showed that inclusion in Group B and younger age (<5-years-old) at repair were independent risk factors for second reoperation. Group B surgical approaches had higher RV-PA systolic pressure gradient at discharge (P=0.02) and required more PA bifurcation repair at the time of second reoperation (P=0.05). Freedom from second reoperation for conduit obstruction was significantly higher in Group A patients at 5 and 8 years (P<0.04) and those with xenografts rather than homograft (P=0.04). CONCLUSIONS: Our results support the optimal surgical approach for RV-PA conduit obstruction is total replacement with a xenograft. RV outflow reconstruction by other techniques without complete dissection of PA bifurcation does not completely relieve the stenosis and could cause early restenosis. Higher systolic gradients at discharge and younger age at first reoperation are predictors of earlier reoperation.     

Prostate cancer after heart transplantation: unicenter case-control study.

BACKGROUND: We have noted an unexpectedly high incidence of prostate cancer in our heart transplant recipients (HTR). METHODS: We conducted a retrospective review of patients after heart transplantation to investigate the prevalence, treatment, and outcome of prostate cancer diagnosed after systematic screening (study group). We compared them with case-matched HTR (control). RESULTS: Among 702 recipients, 15 patients had elevated prostate-specific antigen (PSA) levels. Fourteen cases of prostate cancer were diagnosed and treated. The median time between transplantation and prostate cancer diagnosis was 73 months. No patient was diagnosed in a locally advanced (>T2) or metastatic stage. Eleven patients (78.6%) received curative treatment. During follow-up (median, 44 months), 1 patient died from prostate cancer. The survival rate between the study and control groups did not differ. CONCLUSION: Routine PSA testing is recommended as a screening test for prostate cancer in patients after heart transplantation. We believe this could also result in detection of early stages of prostate cancer, thus allowing curative treatment, and achieving similar survival to other case-matched HTR with no prostate cancer.     

Improvement in quality of life after initiation of lamotrigine therapy in patients with epilepsy in a naturalistic treatment setting.

Quality of life is impaired in patients with epilepsy and can be improved by effective therapy. Randomised clinical trials have shown that lamotrigine treatment is associated with improved quality of life. However, little information is available on quality of life or treatment effects in patients with epilepsy in the general population. The objective of this study was to estimate the impact of lamotrigine on quality of life in a naturalistic treatment setting. The study included adult patients with epilepsy in whom lamotrigine therapy was initiated. Each subject completed the Quality of Life in Epilepsy Inventory (QOLIE)-31 quality of life questionnaire at inclusion and at a follow-up visit in the next 4 months. Demographic information and medical history were provided by the investigator. These were evaluated as potential determinants of change in quality of life using logistic regression. Three hundred and forty-one patients were evaluated, 192 starting lamotrigine in combination with another drug, 90 as a first-line monotherapy, 45 as a switch from another drug and 14 as a reduction to monotherapy from a previous combination. Baseline scores on the QOLIE-31 ranged from 53.8 in the combination group to 69.5 in the first-line group. 34.6% of patients were considered to be responders, with no significant differences between treatment regimen. Most improvement was seen for the energy-fatigue and medication effects subscales and, for the first-line group, seizure worry. Seizure type was the only determinant of improvement of quality of life identified. In conclusion, lamotrigine treatment is associated with improved quality of life, regardless of treatment regimen.     

Cytogenomics of cancers: From chromosome to sequence

The role of acquired chromosomal rearrangements in oncogenesis (cytogenomics) and tumor progression is now well established. These alterations are multiple and diverse and the products of these rearranged genes play an essential role in the transformation and growth of cancer cells. The validity of this assumption is demonstrated by the development of specific inhibitors or antibodies that eliminate tumoral cells by targeting some of these changes. Imatinib, an inhibitor of the tyrosine kinase ABL, the prototype of these targeting drugs, is yielding complete remissions in most CML patients. Knowledge of chromosomal abnormalities is becoming an essential contribution to the diagnosis and prognosis of cancers but also for monitoring minimal residual disease or relapse. The concept of the “cytogenetic uniqueness” of each cancer has resulted in personalized treatment. This investigation will expound upon, besides the recurrent genomic alterations, the numerous products of perverted Darwinian selection at the cellular level.     

Differential apoptotic response of J774 macrophages to alumina and ultra-high-molecular-weight polyethylene particles.

We recently identified apoptosis in in vitro wear particle-stimulated macrophages. The recent explosion of interest in apoptosis lies in the fact that it is under positive and negative regulation through evolutionary conserved biochemical pathways. It may also be possible to modulate macrophage apoptosis in the treatment of periprosthetic osteolysis. The purpose of this study was to compare the macrophage response to identically sized particles of alumina ceramic (Al2O3) and ultra-high-molecular-weight polyethylene (UHMWPE) in terms of TNF-alpha release and induction of apoptosis. J774 mouse macrophages were incubated for 0-24 h in the presence of Al2O3 and UHMWPE particles. TNF-alpha release was measured by ELISA; Poly(ADP-ribose)polymerase (PARP) and caspase-3 expression was analyzed by Western blot; DNA fragmentation (DNA laddering) was visualized on agarose gel containing ethidium bromide. Al2O3 particles induced TNF-alpha release after 4 h incubation with concentrations reaching 483 and 800 pg/ml after 24 h with 125 and 250 particles/macrophage, respectively (control = 161 pg/ml) (P < 0.05 vs. control). The same concentrations of UHMWPE particles induced a much larger and significant TNF-alpha release after only 1 h incubation, increasing up to 6250 pg/ml after 24 h (P < 0.05 vs. control). Western blot analysis demonstrated that the active caspase-3 fragment (17 kDa) and the proteolytic PARP fragment (85 kDa) were expressed after 2 h incubation with 125 and 250 Al2O3 particles/macrophage. The active caspase-3 and the PARP fragment had lower expression and appeared after a longer incubation time (8 h) with 125 and 250 UHMWPE particles/macrophage. Finally, DNA fragmentation (DNA laddering) was observed after 16 h with 125 and 250 particles of Al2O3 per macrophage whereas no laddering was induced by UHMWPE particles even after 24 h incubation. This study shows that although both Al2O3 and UHMWPE particles induce TNF-alpha release, this stimulation was much greater (8-10 times higher) with UHMWPE than Al2O3 (P < 0.05 vs. control). As well, the induction of apoptosis, as measured by activation of caspase-3, PARP cleavage and DNA laddering, is different for these two particles, being faster and more important with Al2O3 than UHMWPE. We hypothesize that the ability of Al2O3 to induce macrophage apoptosis may explain the lower TNF-alpha release observed with these particles and explain the differences seen in osteolysis patterns of ceramic-ceramic (CC) vs. metal-polyethylene (Mpe) articulations. In conclusion, apoptosis may be a major internal mechanism to decrease macrophage activity and may be a desired therapeutic endpoint. The identification of an apoptosis-related pathway in the macrophage response to ceramic particles provides crucial data for a rational approach in the treatment and/or prevention of periprosthetic osteolysis.     

Anatomic variations of the spermatic vein and endovascular treatment of left varicoceles: a pediatric series]

OBJECTIVE: To report on the high incidence of anatomical variants of the origin and course of the internal spermatic vein (ISV) discovered at the time of percutaneous embolization of left varicoceles in a pediatric population. METHODS: We reviewed retrospectively the 65 cases of left varicocele treated by percutaneous embolization (grade II and III) in our institution between 1990 and 2000. The course of the left renal vein (LRV), the origin of the ISV, and the number of ISVs and their pathway were recorded in all cases, according to the B?hren classification. RESULTS: In 37/65 (57%), the ISV was single and arose from a normal LRV (type I). The following variants were encountered: type V--circumaortic LRV 9/65 (14%); type IVb--intrarenal origin of ISV 8/65 (12%); type II--multiple ISV 5/65 (8%); and pelvic collaterals 6/65 (9%). CONCLUSION: Venous anatomical variants are frequently encountered (43%) at the time of left varicocele embolization in children. Such variants often impose some adjustments to the technique of embolization and, at times, hamper the procedure.     

Quantification and pharmacological characterization of dialysate levels of noradrenaline in the striatum of freely-moving rats: release from adrenergic terminals and modulation by α2-autoreceptors

Information concerning striatal levels of noradrenaline (NA) remains inconsistent. Here we have addressed this issue using a sensitive method of HPLC coupled to amperometric detection. The NA reuptake-inhibitor, reboxetine, selectively elevated levels of NA versus dopamine (DA), and NA levels were also selectively elevated by the α₂-adrenoceptor (AR) antagonist, atipamezole. The actions of atipamezole were mimicked by the preferential α_2A-AR antagonist, BRL44408, while JO-1 and prazosin, preferential antagonists at α_2C-ARs, caused less marked elevations in NA levels. In contrast to antagonists, the α₂-AR agonist, S18616, decreased NA levels and likewise suppressed those of DA. Unilateral lesions of the substantia nigra with 6-hydroxydopamine depleted DA levels without affecting those of NA. Further, the D₃/D₂ receptor agonist, quinelorane, decreased levels of DA without modifying those of NA. However, the D₃/D₂ receptor antagonists, haloperidol and raclopride, and the DA reuptake-inhibitor, GBR12935, elevated levels of both DA and NA. Levels of 5-HT (but not of NA or DA) were increased only by the 5-HT reuptake-inhibitor, citalopram. They were decreased by S18616 and prazosin, reflecting the inhibitory and excitatory influence of α₂- and α₁-ARs, respectively, upon serotonergic pathways. In conclusion, NA in the striatum is derived from adrenergic terminals. Its release is subject to tonic, inhibitory control by α₂-ARs, possibly involving both α_2A- and α_2C-AR subtypes, though their respective contribution requires clarification. A role of dopaminergic terminals in the reuptake of NA likely explains the elevation in its levels elicited by DA reuptake-inhibitors and D₃/D₂ receptor antagonists.     

Impact of photon energy recovery on the assessment of left ventricular volume using myocardial perfusion SPECT

BACKGROUND: Photon energy recovery (PER) is a spectral deconvolution technique validated for scatter removal in patients and phantom studies. The purpose of this study was to examine the impact of PER on left ventricular volume measurement based on myocardial perfusion single photon emission computed tomography (SPECT). METHODS AND RESULTS: SPECT acquisitions were performed by use of a static cardiac phantom and in 25 patients after a rest injection of technetium 99m sestamibi by use of multiple energy windows (126-136, 137-144, and 145-154 keV). Data were successively reconstructed with and without PER, by use of iterative reconstruction and post-processing filtering (Butterworth filter; order, 5; cutoff, 0.30 cycles/pixel). Image contrast was evaluated in reconstructed data, and volumes were calculated by use of QGS. PER increased reconstructed image contrast from 62% +/- 2.7% to 84.3% +/- 5.7% in the phantom studies (P <.0001) and from 49% +/- 2% to 73% +/- 2% in patients (P <.0001). Although it remained underestimated (P <.0001), phantom volume was higher after PER correction compared with uncorrected data (50.9 +/- 0.8 mL vs 44.6 +/- 1 mL, P <.0001). The error in volume measurement was decreased by PER correction (16.6% +/- 1.3% vs 27% +/- 1.7% [uncorrected data], P <.0001). In patients, left ventricular volume increased from 83 +/- 10 mL to 91 +/- 10 mL (P <.0001), and the PER-induced volume increase was correlated with the image contrast increase (r = 0.61, P =.001). Finally, the percentage of volume increase was higher in patients with small left ventricular volumes. CONCLUSIONS: PER has a significant impact on image contrast and left ventricular volume measurement by use of perfusion SPECT. PER improves the accuracy of phantom volume assessment. In patients, volume increase is correlated to image contrast increase and is higher in those with small ventricles.