Pressure Recovery in Pediatric Aortic Valve Stenosis

This study was designed to evaluate the phenomenon of pressure recovery in pediatric patients with aortic stenosis and also to evaluate how observed differences between catheter and Doppler gradients can be predicted by Doppler echocardiography. Doppler measurements of aortic valve stenosis gradients are known to overestimate observed gradients in the catheterization laboratory. Pressure recovery has been shown to be a contributing factor to this discrepancy. However, the clinical relevance of correcting Doppler gradients using the pressure recovery equation has not been evaluated in the pediatric population. Simultaneously obtained catheter and Doppler gradients were studied in 14 patients (range, 0.03–18 years; mean, 4.1 years) with aortic valve stenosis. A total of 23 data points were measured because 9 patients underwent balloon valvuloplasty and had both a pre- and a post-balloon valvuloplasty data point in the study. The catheter gradients were then compared to peak, mean, and pressure recovery corrected Doppler gradients. Pressure recovery was calculated using a previously validated equation. As expected, measured echocardiographic continuous-wave peak Doppler gradients overestimated the observed catheter gradients (range, 16–93 mmHg; mean, 43 mmHg). The continuous-wave peak Doppler gradients, mean, and pressure recovery adjusted gradients were equally as good in correlating the observed catheter gradients to those obtained by Doppler echocardiography (r = 0.92). However, pressure recovery corrected Doppler gradients were in better agreement with catheter gradients than echocardiographic mean or peak Doppler gradients (95% limit of agreement: –9 to 19 mmHg for pressure recovery corrected gradients, –30 to 11 mmHg for mean Doppler gradients, and 2–83 mmHg for peak Doppler gradients). Measured continuous-wave peak Doppler gradients consistently overestimated catheter gradients. The noted differences may be predicted using the pressure recovery equation. Pressure recovery is a significant factor in children with aortic valve stenosis.     

Cerebrospinal fluid shunt survival and etiology of failures: a seven-year institutional experience

BACKGROUND: Innovations in shunt technology and neuroendoscopy have been increasingly applied to shunt management. However, the relative life span of shunts and the etiology of shunt failure have not been characterized recently. METHODS: We reviewed the records of all shunting procedures at our institution between January 1992 and December 1998. Independent predictors of shunt failure were analyzed via multivariate Cox regression analysis in 836 shunting procedures. Independent predictors of the etiology of failure (infection, proximal obstruction, distal malfunction) were analyzed via multivariate logistic regression analysis in the 383 shunts which failed. RESULTS: A total of 353 pediatric patients underwent 308 shunt placements and 528 revisions. The risk (hazard ratio; HR) of shunt failure decreased as a function of time in both primary placements and revised shunts. In failed shunts, the odds of infection decreased 4-fold per year of shunt function, while the odds of distal malfunction increased 1.45-fold per year. Increasing number of shunt revisions (HR 1.31, p < 0.05), decreasing patient age in years (HR 1.04, p < 0.001), gestational age <40 weeks (HR 2.15, p < 0.001) but not the etiology of hydrocephalus were associated with an increased risk of shunt failure. Revisions versus primary placements, Dandy-Walker cysts and gestational age <40 weeks were independently associated with proximal, distal and infectious causes of failure, respectively. CONCLUSIONS: The long-term shunt revision rates observed here are similar to those reported over the past 2 decades. Shunt life span remains poorer in shunt revisions and in younger patients. Patient characteristics may suggest a specific risk and mechanism of failure, aiding in the long-term management of shunted hydrocephalus.     

Cytogenetic abnormalities in a hemangiopericytoma of the spleen

To date, only 16 cytogenetically abnormal hemangiopericytomas (HP) have been reported. Despite this low number, some characteristic karyotypic features have already emerged: most HP are near-diploid and breakpoints in 12q13, 12q24, and 19q13 seem to be common, with t(12;19)(q13;q13) being a recurrent translocation. Here, we report the first case of a probably benign splenic HP with chromosomal abnormalities. The abnormal karyotype was 47,XX,t(5;22;11)(q31;q11;q13),+10. None of these abnormalities have previously been reported in HP, suggesting that the karyotypic pattern of splenic HP may differ from soft tissue HP.     

Management of urethral recurrence in patients with Studer ileal neobladder

OBJECTIVE: The overall risk of urethral recurrence (UR) of transitional cell carcinoma (TCC) in patients with orthotopic neobladder ranges from 2% to 6%. We are presenting herein our experience in order to evaluate and define the management of these patients, since the cases with urethral recurrence in patients with orthotopic neobladder are very scarce. MATERIALS AND METHODS: Five hundred and sixteen radical cystectomies due to TCC were performed at our Centre between January 1990 and February 1998. One hundred and thirty-eight of them (26.7%) underwent an orthotopic neobladder procedure with the Studer's technique. We are reviewing five cases of UR in patients with orthotopic neobladder, the cystectomy indications and the differences between the clinical and the pathologic stages. We are also assessing its clinical presentation, diagnosis, treatment and evolution. RESULTS: Five patients (3.6%) from 50 to 71 years old with Studer's orthotopic neobladder presented with UR. All of those neobladders were initially superficial TCC, mostly multifocal, and all had failed the endovesical treatment. Endoscopic treatment was administered in two cases with superficial UR. One patient with urethral CIS received intraurethral BCG instillations. One case because of multiplicity, and another due to the presence of an infiltrating urethral tumour, underwent urethrectomy and neobladder exeresis. In both cases, the intact 15-20cm isoperistaltic proximal ileal limb of the Studer-type orthotopic neobladder was used as an ileal conduit. CONCLUSIONS: UR in patients with orthotopic bladder substitution is unusual. A conservative approach is possible when dealing with superficial recurrences. In cases of urethrectomy, the isoperistaltic proximal ileal limb of the Studer neobladder may be used as an ileal conduit.     

Adenovirus E1a protein enhances the cytotoxic effects of the herpes thymidine kinase-ganciclovir system

Cancer gene therapy based on the use of suicide genes, such as the thymidine kinase gene, is not producing satisfactory results. Several approaches have been delineated to enhance the therapeutic responses, including augmentation of the bystander effect, the combination of the herpes simplex virus thymidine kinase-ganciclovir (HSVTK-GCV) system into replication competent adenoviruses and others. Moreover, because usually less than 20% of human malignant cells are in S-phase, the HSVTK-GCV system is not as efficient as expected. To increase the cytotoxic effects of the HSVTK-GCV system, we hypothesized that concomitant expression of E1a protein, which drives cells to proliferation and S-phase, could increase the effects of the HSVTK-GCV system. Several retroviruses were constructed carrying bicistronic sequences of TK and E1a 12S genes under the control of the CMV promoter. The constructions were tested in murine (NIH-3T3, MSC11A5) and human cells (IMR90, HeLa, MDA-MB435). A clear increase of the HSVTK-GCV system killing effect in nonconfluent cells was observed in the cells studied, especially in NIH-3T3, MSC11A5, IMR90, and MDA-MB435 expressing cells. In confluence, the NIH3T3 and IMR90 E1a-TK-expressing cells were also very sensitive and most malignant E1a-TK-expressing cells showed an irreversible G2-M cell cycle arrest. Moreover, the concomitant expression of adenovirus E1a and the HSVTK-GCV system increased the sensitivity to anticancer agents such as cisplatin. These results show that adenovirus E1a protein expression clearly enhances the cytotoxic effects of the HSVTK-GCV system and the response to treatment with cisplatin.     

Supervivencia a largo plazo con quimioterapia a altas dosis de rescate en pacientes con cáncer de células germinales metastásico. Análisis de los patrones de recidiva

Objective

To evaluate survival and relapse patterns in 13 patients with recurrent, or refractory, germ-cell tumours treated with high-dose chemotherapy (HDC) and with peripheral blood stem-cell support.

Material and methods

All patients were treated in a single centre and received a median of 9 cycles (range 3–13) of cisplatinum-based chemotherapy (CT). The protocol consisted of: a) induction with ifosfamide-based CT (EPI: VP16 120 mg/m², ifosfamide 1.3 g/m², cisplatinum 25 mg/m²×4 days); b) mobilisation of PBSC with of either G-CSF (10 ug/kg/day) in 2 patients or EPI plus G-CSF, and c) HDC (carboplatin 350 mg/m², cyclophosphamide 1500 mg/m², VP16 400 mg/m²×3 days). G-CSF (5 μg/kg) was administered until haematopoietic graft. Median age=32 years (range 20–52); tumours=10/11 testicular (1 seminoma), 2 mediastinal. HDC was administered 21 months (range 6–66) post-diagnosis. Inclusion criteria: failure to achieve CR with conventional CT (n=5 patients), poor-prognosis mediastinal tumour (n=1), first recurrence after cisplatinum and ifosfamide-based CT (n=2) and second or third relapse (n=5). At the conclusion of HDC, 9/13 patients were in CR, 1 patient did not receive HDC because CNS progression but was included for survival analysis.

Results

Median times to graft were 9 and 13 days for leukocytes and platelets, respectively. Non-haematological toxicity was low and no therapy-related deaths occurred. Median disease free and overall survival were 19 and 30 months, respectively. Currently, 2 patients have not relapsed at 36 and 80 months. Previously-affected sites of disease were the unique sites of relapse in 5/11 (50%), concomitant distant relapse in 4/11 patients, CNS metastases in 1 patient. Rescue CT consisted of either oral VP16 or CBDCA/Taxol, which induced a new response in 6/10 patients.

Conclusions

HDC achieves 20% improved survival in patients refractory to conventional chemotherapy and non-resectable tumours. No benefit was observed in HDC treatment in patients having only partial response to conventional chemotherapy. Relapse following HDC occurred mainly at previously affected sites.     

Perception of adolescent mothers on paternal participation in pregnancy,birth, and child rearing

Paternal participation in adolescents' pregnancy is little discussed. Although the absence of the partner is pointed out as one of the problems due to it. This research had the aim to ascertain, under the perspective of mothers who gave birth at an early age, the participation of a father during gestation, birth, and raising of his child in the first months of life. In order to record data, two categories have been devised: experiencing pregnancy and valuing a partner/father's presence and participation.