Relationship of sigma activity to sleep interictal epileptic discharges: a study in children affected by benign epilepsy with occipital paroxysms

Introduction: By applying spectral analysis techniques we recently showed that Interictal Epileptic Discharges (IEDs) are modulated by sleep spindle synchronization mechanisms (sigma activity, SA, 12.0–16.0 Hz). This finding applies to both benign epilepsy of childhood with rolandic spikes (BECRS), to symptomatic epilepsy of childhood strongly activated by sleep and to the Landau–Kleffner syndrome. These results are quite different from those found in adult partial epileptic patients where slow wave activity (SWA, 0.5–4.5 Hz) plays the main role in the modulation of IEDs during sleep. This finding could suggest that the activation of IEDs by spindle activities could be an age-related feature of epilepsy. In order to verify this hypothesis we studied a group of epileptic children performing a polysomnographic study on five patients with BEOP strongly activated by sleep. Methods: We performed overnight continuous EEG-polysomnographic studies in five patients (mean age 6.0±2.5). The IEDs count was performed on the most active occipital lead. The temporal series of SWA and SA values, derived from spectral analysis, were obtained from a spike-free central, controlateral lead. Relationships between SA, SWA and time series of IEDs were tested by means of correlation techniques after data normalization. Results: Our results revealed a significantly higher correlation between IEDs and SA with respect to SWA in all subjects, in total sleep time. When the analysis was limited only to NREM sleep the correlation between sigma and IEDs was even more impressive. Conclusions: Data suggest that also in BEOP the spindle generating mechanism modulates the IEDs during sleep. This mechanism seems to be an age-dependent phenomenon with no relation whatsoever either with the type of epilepsy or with the brain region.     

Localized unresectable neuroblastoma: results of treatment based on clinical prognostic factors.

BACKGROUND: We previously reported that stage 3 neuroblastoma comprises (i) a low-risk group including all infants (age 0-11 months) as well as older children with non-abdominal primaries, and (ii) a high-risk group made up of children >1 year of age with abdominal primaries. Aggressive chemotherapy was effective only in the latter group. PATIENTS AND TREATMENT: On this basis, in 1990 we designed a new protocol by which all low-risk patients received standard-dose chemotherapy, while the high-risk ones received very aggressive chemotherapy. RESULTS: Between November 1990 and December 1997 a total of 95 eligible and evaluable children were enrolled: 47 were low-risk (35 infants and 12>1 year of age at diagnosis and having non-abdominal primaries), and 48 were high-risk (being >1 year of age and having abdominal primaries). Of the 47 low-risk patients, five relapsed and four subsequently died. The 5-year overall survival (OS) was 91%. Of the 48 patients in the high-risk group, 22 relapsed or progressed, 18 of whom died from their disease and two from toxicity, and one was lost to follow-up. The 5-year OS was 60%. Univariate analysis showed that age, site of primary, risk-group, urine vanillylmandelic excretion, plasma levels of lactate dehydrogenase, ferritin and neurone-specific enolase, and MYCN status correlated with outcome. However, multivariate analysis showed that only MYCN status retained prognostic value. CONCLUSIONS: In low-risk stage 3 neuroblastoma, standard-dose chemotherapy is associated with an excellent chance of being cured. Aggressive chemotherapy is effective for high-risk patients, but results are still unsatisfactory. MYCN gene amplification is a prognostic indicator for most, but not all, treatment failures.     

Prolonged epidural infusions of ropivacaine (2 mg/mL) after colonic surgery: the impact of adding fentanyl

We evaluated the safety and efficacy of a 72-h epidural infusion of ropivacaine and measured the impact of adding fentanyl 2 microg/mL to the required infusion rate, on the quality of postoperative pain relief and the incidence of side effects, after colonic surgery. One hundred fifty-five patients scheduled for elective colonic surgery were randomized in this trial. Epidural infusions of ropivacaine 2 mg/mL with fentanyl 2 microg/mL (R + F) and without fentanyl (R) were commenced during surgery and continued for 72 h postoperatively. This was a prospective, randomized, double-blinded, multi-center trial. The median infusion rate required was less in the R + F group (9.3 vs 11.5 mL/h, P < 0.001). Median pain scores at rest and on coughing were lower in the R + F group (P < 0.0001). The incidence of hypotension was more in the R + F group (P = 0.01). Time to readiness for discharge was delayed in the R + F group (median 6.6 vs 5.5 days, P = 0.012). The addition of fentanyl to ropivacaine resulted in decreased infusion rates and enhanced pain control; however, adverse effects were increased and readiness to discharge was delayed. IMPLICATIONS: Epidural infusions of ropivacaine with and without fentanyl were administered to patients to control pain after colonic surgery. Patients who received ropivacaine with fentanyl had better pain control, increased side effects, and delayed readiness to discharge. This study questions the value of adding opioids to epidural infusions of local anesthetics.     

Direct effect of the correction of acidosis on plasma parathyroid hormone concentrations, calcium and phosphate in hemodialysis patients: a prospective study

BACKGROUND: Metabolic acidosis contributes to renal osteodystrophy and together with hyperphosphatemia, hypocalcemia and altered vitamin D metabolism may result in increased levels of intact parathyroid hormone (iPTH) and metastatic calcifications. However, the impact of the correction of metabolic acidosis on iPTH levels and calcium-phosphate metabolism is still controversial. STUDY DESIGN: The effects of the correction of metabolic acidosis on serum concentrations of iPTH, calcium (Ca), phosphate (PO(4)) and alkaline phosphatase were prospectively studied. Twelve uremic patients on maintenance hemodialysis (HD) for 49 months (median; range 6-243 months) with serum bicarbonate levels < or =20 mmol/l were studied before and after 3 months of oral sodium bicarbonate supplementation. Predialysis serum bicarbonate, arterial pH, ionized calcium, plasma sodium, plasma potassium, serum creatinine, hemoglobin, K(t)/V, postdialysis body weight, predialysis systolic and diastolic blood pressure were also evaluated before and after correction. RESULTS: Serum bicarbonate levels and arterial pH increased respectively from 19.3 +/- 0.6 to 24.4 +/- 1.2 mmol/l (p < 0.0001) and 7.34 +/- 0.03 to 7.40 +/- 0.02 (p < 0.001). iPTH levels decreased significantly from 399 +/- 475 to 305 +/- 353 pg/ml (p = 0.026). No changes in total serum Ca, plasma PO(4), serum akaline phosphatase, K(t)/V, serum creatinine, hemoglobin, body weight, predialysis systolic and diastolic blood pressures were observed. iCa decreased significantly. CONCLUSIONS: Our study demonstrates that the correction of metabolic acidosis in chronic HD patients reduces iPTH concentrations in HD patients with secondary hyperparathyroidism possibly by a direct effect on iPTH secretion.     

Carboplatin and 5-fluorouracil in poor performance status patients with advanced urothelial cancer

BACKGROUND: In view of the difficulties in administering aggressive treatmentto elderly patients, frequently with concomitant medical problems,a treatment program with the combination of carboplatin and5-FU for advanced urothelial tumors was designed. The aim wasto maintain an efficacious therapeutic schedule while minimizingtoxicity. PATIENTS AND METHODS: Twenty-three patients with advanced bidimensionally measurableurothelial carcinoma were given carboplatin 100 mg/m² and 5-fluorouracil500 mg/m² days 1–3 which was escalated to carboplatin125 mg/m² and 5-fluorouracil 625 mg/m². 5 patients were >70 years, the ECOG performance status was 2–3 in 10 patients(43%), and the creatinine was > 2.0 mg/dl in 3 patients (13%).Five patients (22%) had pre-existing cardiac disease, and Ihad hepatopathy. Nine patients (39%) had prior cisplatin. RESULTS: Ten patients remained at level 1, and 12 others had the dosageescalated to level 2. Twenty-one patients are evaluable forresponse. Response was observed in 5 of 21 (24%) evaluable patients(95% confidence limits 15%–33%), only at dose level 2.There was 1 CR (5%) and 4 PR (19%). There were no responsesin patients who had prior DDP versus 5 of 13 (38%) responsesin patients who had not had prior DDP. The median time to responsewas 2 months. The median duration of response was 8 months.At level 2 myelotoxicity was significant, and led to a returnto level 1 in 2 patients. Nine of 12 patients (75%) treatedat level 2 had grade 3 leukopenia, and 1 patient had nadir sepsis.4 patients (33%) had grade 4 thrombocytopenia. CONCLUSIONS: Moderate activity was shown with this regimen in untreated patientsat level 2. This regimen presents a feasible outpatient alternativefor patients who are unable to undergo more aggressive chemotherapy. carboplatin, chemotherapy, poor performance status, transitional cell carcinoma, urothelium     

Pleuropulmonary blastoma: management and prognosis of 11 cases

BACKGROUND: Pleuropulmonary blastoma (PPB) is a rare and aggressive malignant tumor that affects children and adults. This neoplasm is histologically characterized by primitive blastema and a malignant mesenchymal stroma that often demonstrates multidirectional differentiation. Despite the introduction of multimodal therapy, the prognosis of patients with PPB remains poor. METHODS: In the current study the authors reported on PPB cases from a national retrospective search performed in 18 Italian Associations for Pediatric Hematology and Oncology centers. Clinical data, surgical notes, pathologic findings, and summaries of chemotherapy and radiotherapy were obtained from reports and correlated with outcome by standard statistical methods. RESULTS: The series included 11 patients (7 boys and 4 girls) with a median age of 32 months. Respiratory distress was the most common clinical symptom. In three patients the PPB developed from other primary dysplastic diseases: cystic adenomatoid malformation in one case and congenital lung cysts in the other two cases. Five patients experienced disease recurrences (local recurrence in three patients and distant metastasis in two patients, within the central nervous system and an intraocular location, respectively). Patients with a type 2 histologic pattern and/or pleural involvement were found to have a worse outcome compared with patients without such features. Event free survival at 2 years from the time of diagnosis was 45% for all patients. Overall survival at 2 years was 72% for all patients. CONCLUSIONS: PPB is an aggressive neoplasm of early childhood and to the authors' knowledge no adequate therapy has been defined to date for patients with PPB. After making the diagnosis, the main goal of therapy should be radical surgery, even in patients with microscopic residual disease. Because the response to chemotherapy is poor, the authors' experience suggests that chemotherapy should be given with local radiotherapy in the majority of patients.     

Alveolar soft part sarcoma in children and adolescents: A report from the Soft-Tissue Sarcoma Italian Cooperative Group

Background:Alveolar soft part sarcoma (ASPS) is a rare malignanttumor and little is known about its clinical features and management. Wereport on a series of 19 pediatric patients managed over 20 years. Patients and methods:Primary conservative surgery was performedin all patients and was radical in nine, non-radical in three; seven patientsunderwent biopsy alone (3 unresectable tumors, 4 metastatic disease). In twocases radical surgery was performed after primary chemotherapy. Radiotherapywas delivered to 8 patients, chemotherapy to 15. Results:After a median follow-up of 74 months, the five-yearsurvival was 80% for the whole series, 91% for patients withlocalized disease, 100% for patients with tumor 5 cm, and31% for those >5 cm; 16 of 19 patients were alive (12 of 12 withgrossly-resected tumor in first continuous remission). Chemotherapy achievedtwo partial remission among seven evaluable patients. Conclusions:Pediatric ASPS has a more favorable prognosis thanits adult counterpart. In this series, tumor size correlates with metastaticdisease at onset and is the major factor influencing survival. Surgery is themainstay of therapy. The effectiveness of adjuvant therapy remains to beestablished, though radiotherapy may be advisable in cases of inadequatesurgery.