Severe hypoplasia of medullary arcuate nucleus: quantitative analysis in sudden infant death syndrome

The human arcuate nucleus (ARCn) is postulated to be homologous to ventral medullary cells involved in chemoreception, and respiratory and blood pressure responses. Abnormalities in central respiratory control may result from dysfunction of this anatomic ventral area. We evaluated the changes of the neuronal population of the medullary ARCn in infants victims of the sudden infant death syndrome (SIDS). In this study we tested the hypothesis that anatomical deficiency of the ARCn is associated with SIDS. The volume and neuronal density of the ARCn were morphometrically quantified with an image analyzer in 36 cases of SIDS and 12 age-matched controls. We found a marked hypoplasia in the SIDS ARCn compared to controls and, particularly, in 11 SIDS cases (30%) in which the ARCn exhibited a severe hypoplasia, being almost totally absent. Three-dimensional reconstructions and morphometric measurements of ARCn confirmed this marked hypoplasia in all the serial sections examined (P = 0.0001) and the reduced neuronal density (P = 0.0025) in relation to control cases. In conclusion these abnormalities observed in the ARCn are consistent with the idea that ARCn dysfunction plays an important role among the causative factors of sudden infant death. The hypoplasia of the ARCn represents the most frequent congenital abnormality in our experience, and can be a plausible morphological substrate for a subset of SIDS. Received: 11 May 1999 / Accepted: 6 August 1999     

Evaluation of the health effects of the new driving penalty point system in the Lazio Region, Italy, 2001-4.

OBJECTIVE: The penalty point system was introduced in Italy in June 2003. The aim of this study was to evaluate the health effects of this legislation in the Lazio region. METHODS: Poisson models were used to compare emergency department visits, hospitalizations and death between the pre-law and post-law periods (July 2001-June 2003; July 2003-June 2004). RESULTS: The emergency department visit rate ratio (RR) of the two periods was 0.87 (95% confidence interval (CI) 0.86 to 0.88); the corresponding hospital admission RR was 0.87 (95% CI 0.84 to 0.9). The death RR was 0.93 (95% CI 0.82 to 1.05). CONCLUSION: After the legislation was introduced, there were fewer visits to the emergency department, hospitalizations and death from road traffic injuries. However, the effect was lower than expected, and it decreased over time.     

Paradoxical scalloped placenta with polyhydramnios in twin-twin transfusion syndrome.

OBJECTIVE: To describe the paradoxical occurrence of a scalloped placenta in the presence of polyhydramnios and assess its clinical significance in pregnancies complicated by twin-twin transfusion syndrome (TTTS) treated with laser therapy. METHODS: All patients who underwent laser therapy for TTTS between January 2003 and April 2004 were studied. TTTS was diagnosed and staged using the Quintero staging system. Normally the placenta is characterized by undulations of the fetal-placental surface visible by ultrasound (scalloped placenta). Patients with polyhydramnios will typically have a flattened, smooth, non-scalloped placenta. Operative tapes were reviewed and placental type assigned. Pre-, intra-, and postoperative characteristics of each study patient were obtained. RESULTS: Fifteen of 120 patients (12.5%) were noted to have a scalloped placenta despite having polyhydramnios. There was no difference in mean gestational age at laser treatment (20.3+/-0.5 vs. 19.6+/-0.6 weeks, p=0.66) or in stage (p=0.07) between the two groups. The median and range preoperative maximum vertical pocket (MVP) in the recipient gestational sac differed significantly between the scalloped and non-scalloped patients (8.3 (8-12) vs. 10.5 (8-17), p=0.001). All 15 patients (100%) with a scalloped placenta required an amnioinfusion to expose all vascular anastomoses, while amnioinfusion was necessary in only 28 of the 105 patients (26.7%, p<0.001) with a non-scalloped placenta. Postoperative patent placental vessel was identified by surgical pathology in 6.7% of the scalloped placenta group vs. 1.9% of the non-scalloped placenta group (p=NS). CONCLUSION: The definition of TTTS requires an MVP>or=8 cm in the recipient sac. Most patients will have a flattened placenta as a result of polyhydramnios in this sac. Our data show that a paradoxical scalloped placenta may still be present in approximately 12.5% of patients. This preoperative sonographic finding alerts to the potential need for amnioinfusion during laser therapy for TTTS to disclose all vessels to avoid missing placental vascular anastomoses. Amniocenteses should be avoided if possible in patients considering laser therapy to minimize the likelihood of iatrogenic placental scalloping.     

Challenges of Childhood TB/HIV Management in Malawi

The diagnosis and management of childhood tuberculosis (TB) are major challenges in countries such as Malawi with high incidence of TB and human immunodeficiency virus (HIV) infection. Diagnosis of TB in children often relies only on clinical features but clinical overlap with the presentation of HIV and other HIV-related lung disease is common. The tuberculin skin test (TST), the standard marker of M. tuberculosis infection in immune competent children, has poor sensitivity in HIV-infected children and is not usually available in Malawi. HIV test should be routine in children with suspected TB as it improves clinical management. HIV-infected children are at increased risk of developing active disease following TB exposure which justifies the use of isoniazid preventive therapy (IPT) once active disease has been excluded but this is difficult to implement and appropriate duration of IPT is unknown. HIV-infected children with active TB experience higher mortality and relapse rates on standard TB treatment compared to HIV-uninfected children, highlighting the need for further research to define optimal treatment regimens. HIV-infected children should also receive appropriate supportive care including cotrimoxazole prophylaxis and anti-retroviral treatment (ART) if indicated. There are concerns about concurrent use of some anti-TB drugs such as rifampicin with some ARTs.     

The infrequent association of synchronous renal and colonic malignancies

The coexistence of both kidney and colon primary malignancies is a rare condition. We report the case of a 75-year-old woman who presented with bilateral pulmonary nodules at chest X-ray and stratigraphy. Total-body CT scan showed multiple, apparently metastatic, bilateral pulmonary lesions, a diffusely dysomogeneous neoformation in the lower pole of the right kidney and a gross neoformation in the ascending colon. A right nephrectomy and a right hemicolectomy were performed and histology showed two primary neoplasms: clear cell renal carcinoma and undifferentiated adenocarcinoma of the colon.     

Repeated exposure of rats to JP-4 vapor induces changes in neurobehavioral capacity and 5-HT/5-HIAA levels

Thirty-two Sprague-Dawley rats were exposed for 6 h/d for 14 consecutive days to JP-4 jet fuel vapor (2 mg/L) or room air control conditions. Following a 14- or 60-d recovery period, rats completed a battery of 8 tests selected from the Navy Neurobehavioral Toxicity Assessment Battery (NTAB) to evaluate changes in performance capacity. Exposure to JP-4 vapor resulted in significant changes in neurobehavioral capacity on several tests that varied as a function of the duration of the recovery period. Rats were evaluated for major neurotransmitter and metabolite levels in five brain regions and in the blood serum. Levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were shown to be significantly elevated in several brain regions as well as in the blood serum in the vapor-exposed groups. Results of the rat study are compared to previously reported neurobehavioral evaluations of European manufacturing personnel exposed chronically to jet fuel vapor.     

Gemcitabine as second-line treatment for advanced non-small-cell lung cancer: A phase II trial.

PURPOSE: To investigate the activity and toxicity of gemcitabine as a single agent in patients with advanced non-small-cell lung cancer (NSCLC) after recurrence or failure of previous treatment with a platinum-containing regimen. PATIENTS AND METHODS: From November 1995 to October 1997, 83 patients with stage IIIB or IV NSCLC received gemcitabine 1,000 mg/m(2) once a week for 3 weeks every 28 days. Responses were assessed every two treatment courses. The median age of the patients was 63 years; Eastern Cooperative Oncology Group performance status was 0 to 1 in 62 patients and 2 in 21 patients. The predominant histology was squamous (39 patients); 49 patients had stage IV disease and 34 patients had stage III disease (33 stage IIIB and one stage IIIA). RESULTS: Sixteen patients (19%) achieved a partial response to treatment; the median duration of response was 29 weeks (range, 6 to 50 weeks). Treatment was well tolerated: grade 2 to 3 (World Health Organization standardized response criteria) leukopenia and thrombocytopenia occurred in 23% and 20% of patients, respectively. Mild asthenia was observed in 16% of patients, and peripheral edema in 5% of patients. Nausea and vomiting were present in 16% of patients. CONCLUSION: In this experience, gemcitabine showed significant activity without relevant toxicity, mainly in patients who were previously responsive to chemotherapy. This suggests a possible role for gemcitabine as a second-line treatment in patients who had a previous response or achieved stable disease with a platinum-containing regimen.     

Intensive sequential chemotherapy (ISC 95) with growth factors and blood stem cell support in high-intermediate and high-risk (IPI 2 and IPI 3) aggressive non-Hodgkin's lymphoma: an oligocentric report on 42 patients.

We previously reported feasibility and efficacy of a monocentric pilot study of intensive sequential chemotherapy (ISC) in poor-risk aggressive non-Hodgkin's lymphoma (NHL) in patients < 60 years. To validate these results on a large cohort of patients, we designed a new and oligocentric study. After a COP (cyclophosphamide (Cy), vincristine (Vcr), prednisone (Pred) debulking, patients received four courses of high-dose CHOP (Cy, doxorubicin (Doxo), Ver, Pred), with the addition of etoposide and cisplatin during the two last courses. G-CSF was delivered after each cycle, and peripheral blood stem cells (PBSC) were used to support the two last cycles. Total duration of chemotherapy was 13 weeks, with a planned dose-intensity (DI) of 1420 mg/m2/week and 23 mg/m2/week for Cy and Doxo, respectively. Radiotherapy (involved fields) was then delivered for patients with node size > or = 5 cm at diagnosis. Forty-two patients were enrolled in this study; 36 completed the treatment and received 75% or more of the planned DI for both Cy and Doxo. Median duration of grade 4 neutropenia was 14 days (range, 2 to 28) for the regimen as a whole, and median duration of rehospitalization for febrile neutropenia was 18 days (range, 4 to 41). Overall response rate was 83%, with 29 patients (69%) in complete response (CR). Six patients failed to respond and one died of toxicity. With a median follow-up of 22.5 months (range, 10 to 42), the 3-year event-free survival (EFS) is 55% (95% CI, 39-71), while disease-free survival (DFS) is 79% (95% CI, 63-95). Ambulatory ISC is accessible and feasible in an oligocentric study. PBSC allow repeated delivery of high-dose chemotherapy cycles, and result in encouraging CR, EFS, and DFS rates for poor-risk aggressive NHL's patients.     

Weekly gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase II study

Background: The combination of gemcitabine and cisplatin has proven effective in the treatment of advanced non-small-cell lung cancer (NSCLC). However, the optimal schedule for administration of the two drugs has not yet been determined. In this study we evaluated the activity and toxicity of a weekly gemcitabine and cisplatin schedule.Patients and methods: Thirty-six untreated patients with stage IIIB–IV NSCLC entered the study. Treatment consisted of gemcitabine 1000 mg/m2 i.v. and cisplatin 35 mg/m2 i.v., both given weekly on days 1, 8, and 15, followed by one week of rest.Results: Ninety-seven courses (273 weekly administrations) were delivered. The median dose-intensity was 612 mg/m2 per week for gemcitabine (82%) and 21 mg/m2 per week for cisplatin (80%). All 36 of the patients were evaluable for toxicity, and 30 for response. Partial remissions were observed in 12 patients, for an overall response rate of 40% (95% confidence interval (95% CI): 22.5%–57.5%). Most of the partial remissions were seen in IIIB patients (54% of the stage IIIB and 22% of the stage IV patients responded). According to the intent-to-treat principle, the response rate was 33.3% (12 of 36 patients). The median response duration was 9.9 months (range 4–23) and the median survival time 11.8 months (range 1–24). World Health Organization (WHO) grade 3–4 myelotoxicity was: thrombocytopenia in nine patients (25%), neutropenia in six (16.6%) and anemia in six (16.6%); there was very little additional major toxicity.Conclusions: This regimen appears to be active and to have a favourable toxicity profile.