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H P McDowell

Publications and source records attributed to H P McDowell.

16 recordsLinked to original sources
PubMed2006

Morphological and molecular assessment of apoptotic mechanisms in peripheral neuroblastic tumours.

Multiple defects in apoptotic pathways have been described in peripheral neuroblastic tumours (NTs). Mitosis-karyorrhexis index (MKI) is a reliable morphological marker identifying favourable and unfavourable NTs. The extent to which apoptotic processes contribute to determine the clinical significance of MKI is still undefined. Apoptosis was investigated in a series of 110 peripheral NTs by comparing MKI to immunohistochemical and molecular apoptotic features. High MKI was found in 55 out of 110 NTs (50%) and was associated with advanced stage (P = 0.007), neuroblastoma (NB) histological category (P = 0.024), MYCN amplification (P < 0.001), and poor outcome (P = 0.011). Overall survival probability was 45% in patients with high MKI compared to 73% in patients with low MKI. In the same 110 NTs, the expression of Bcl-2, Bcl-XL, Bax and Mcl-1 was studied by immunohistochemistry, but no significant associations were found with clinicohistological features. Microarray analysis of apoptotic genes was performed in 40 out of 110 representative tumours. No significant association was found between the expression of apoptotic genes and MKI or clinicohistological features. Proliferative activity was assessed in 60 out of 110 representative tumours using Ki67 immunostaining, but no significant correlations with MKI or clinicobiological features were found. In NTs, the combination of apoptosis and proliferation as expressed by MKI is a significant prognostic parameter, although neither of them is per se indicative of the clinicobiological behaviour and outcome.

Adolescent↗
PubMed2004

Oscillations in NF-kappaB signaling control the dynamics of gene expression.

Signaling by the transcription factor nuclear factor kappa B (NF-kappaB) involves its release from inhibitor kappa B (IkappaB) in the cytosol, followed by translocation into the nucleus. NF-kappaB regulation of IkappaBalpha transcription represents a delayed negative feedback loop that drives oscillations in NF-kappaB translocation. Single-cell time-lapse imaging and computational modeling of NF-kappaB (RelA) localization showed asynchronous oscillations following cell stimulation that decreased in frequency with increased IkappaBalpha transcription. Transcription of target genes depended on oscillation persistence, involving cycles of RelA phosphorylation and dephosphorylation. The functional consequences of NF-kappaB signaling may thus depend on number, period, and amplitude of oscillations.

Active Transport, Cell Nucleus↗
PubMed2003

Update on childhood rhabdomyosarcoma.

The overall survival of childhood rhabdomyosarcoma has improved dramatically over the past 10 years. Early diagnosis and appropriate referral to a specialised centre leading to an accurate and timely diagnosis reflects on overall outcome. Recent molecular studies have identified different biological subtypes resulting in the recognition of poorer subgroups and allowing more appropriate treatment to be administered. Clinical trials remain the cornerstone to further improve outcome, now carried out on an international basis.

Antineoplastic Agents↗
PubMed2001

Localized paediatric orbital rhabdomyosarcoma: influence of imaging on treatment.

AIM: Orbital rhabdomyosarcoma is the most common primary malignant orbital tumour in children and has a good prognosis. The purpose of this paper was to review the imaging and consequent treatment of patients with localized orbital rhabdomyosarcoma from around the U.K. MATERIALS AND METHODS: Patients were identified through the U.K. Children's Cancer Study Group (UKCCSG) database. Investigations and therapy were dictated by the Malignant Mesenchymal Tumour '89 (MMT89) protocol. Imaging and radiological reports of 16 patients from 12 centres were reviewed. The number of patients receiving radiotherapy, timing of radiotherapy, and adherence to treatment protocols were assessed. RESULTS: Local radiologists' reports and imaging techniques varied between sequential examinations and centres. The imaging was adequate for management. No reports quoted measurements of the tumours. Treatment protocols were not always followed rigidly with regard to a residual mass at day 80 post-diagnosis. However, the protocol was not explicit for all outcomes. Fifteen out of 16 patients eventually received radiotherapy. CONCLUSION: There is no standardization of imaging between centres. The presence or absence of a post-therapeutic residue should be stated in the radiology report. Further investigation is needed to differentiate between fibrosis and recurrent tumour. Radiotherapy for residual mass at day 80 is probably more important than standardizing radiological technique.

Adolescent↗
PubMed1998

Pancreatic inflammatory tumour: a rare entity in childhood.

Pancreatic tumours are rare childhood neoplasms. Inflammatory myofibrohistiocytic tumours (IMTs) represent an uncommon but distinct pathological subgroup that creates diagnostic and therapeutic dilemmas. We report a case of IMT arising from the body and tail of the pancreas in an 8-year-old girl presenting with a mass and abdominal pain. A locally aggressive tumour with no evidence of distant metastasis was encountered at laparotomy and resected. Pathologically, the tumour revealed a mixed inflammatory cell infiltrate with myofibrohistiocytic proliferation. These features can resemble a sarcoma. A review of the literature is provided which emphasises the clinical features, pathological findings, and management strategies for these unusual tumours. Complete surgical excision, aided by radiological surveillance, appears to offer the best guidelines for definitive management.

Child↗
PubMed1997

SIOP Working Committee on psychosocial issues in pediatric oncology: guidelines for communication of the diagnosis.

This is the fourth official document of the SIOP Working Committee on psychosocial issues in pediatric oncology constituted in 1991. This document develops another topic discussed and approved by the SIOP Committee: "communication of the diagnosis" is addressed to the pediatric oncology community as guidelines that could be followed. The highly stressful nature of the diagnostic period must be acknowledged, and communication involving the staff and all family members should cover both medical and psychosocial issues. A well-planned and extensive initial session should be followed by continuing discussions. The goal is a knowledgeable family that can talk openly with its members and with the staff.

Adolescent↗
PubMed1997

High-dose cyclophosphamide for poor-prognosis and recurrent pediatric brain tumors: a dose-escalation study.

PURPOSE: To determine the maximum-tolerated dose (MTD) of cyclophosphamide (CTX) when administered over 2 consecutive days followed by hematopoetic stem-cell rescue given as two sequential courses to children with glioblastoma multiforme, poor-prognosis pontine gliomas, and other recurrent CNS tumors. PATIENTS AND METHODS: Two identical doses of CTX were administered 24 hours apart to 14 children and followed by hematopoetic stem-cell rescue. This treatment was repeated immediately following hematologic recovery. The starting dose of CTX was 2.5 g/m2/d with increments of 0.5 g/m2/d. CTX pharmacokinetics and metabolism were measured during 22 courses of treatment. Toxicity and tumor response were recorded. RESULTS: There were two toxic deaths at the dose level of 4 g/m2/d. These were not clearly related to cardiac toxicity and may have been due to generalized capillary leak syndrome. Thus, the MTD of CTX was 3.5 g/m2/ d. There were six complete responses (CRs) (46%; (95% confidence interval [CI], 19% to 73%) and four partial responses (PRs) (31%; 95% CI, 6% to 56%), and one patient achieved stable disease. All children with intracranial primitive neuroectodermal tumors (PNETs) improved following CTX. The median duration of tumor response was 6 months (range, 4 to 29) and only one patient remains disease-free following CTX alone. Overall survival is 21% (95% CI, 13% to 29%) at a median follow-up time of 27 months (range, 12 to 34). CONCLUSION: The MTD of CTX when followed by hematopoetic stem-cell rescue is 3.5 g/m2 administered on each of 2 consecutive days. This treatment was tolerable in children with poor-prognosis brain tumors and produced complete responses in children with recurrent PNETs.

Adolescent↗
PubMed1991

Clinical evaluation of ticarcillin, with clavulanic acid, and gentamicin in the treatment of febrile episodes in neutropenic children.

To assess the clinical efficacy of ticarcillin, with clavulanic acid, and gentamicin, we conducted a prospective one year study of febrile episodes in neutropenic children. Seventy-five episodes were evaluated in 42 children. The response rate was 32% during persistent neutropenia, whilst another third of episodes responded with neutrophil recovery. Positive blood cultures occurred in 21 episodes and 20 of 24 micro-organisms belonged to the 'community' flora, i.e. organisms carried by healthy people (Streptococcus pneumoniae, Staphylococcus aureus, Branhamella catarrhalis and Escherichia coli). The route of pathogenesis was endogenous in 76% of the patients. There was a substantial superinfection-related morbidity (14%) and mortality (7%), related to emergence of resistance during and after parenteral antibiotic administration. The poor clinical response, combined with emergence of resistance, lead to the conclusion that this combination is of limited value as a first line regimen for neutropenic patients.

Child↗
PubMed1988

Isolated pulmonary histiocytosis.

Pulmonary disease in the 'histiocytosis syndromes' is not uncommon. Isolated pulmonary histiocytosis, however, is rarely diagnosed. We describe three patients with this condition, with ages ranging from 3 weeks to 9 1/2 years, in whom there was no evidence of disease in any other organ. Their presentation, treatment, and clinical progress over three years of follow up are discussed.

Child↗
PubMed1987

Acute lymphoblastic leukaemia: trimethoprim resistant organisms during treatment.

A cross sectional study was carried out in children receiving treatment for acute lymphoblastic leukaemia to determine the prevalence of trimethoprim resistant organisms in their gut flora and to compare this with a control population. There was a significantly higher prevalence of trimethoprim resistant bacteria in the study group (61%) compared with controls (14%). A longitudinal study showed that emergence of these organisms was intermittent during treatment.

Child↗
PubMed1986

Implantable subcutaneous venous catheters.

Twelve totally implantable subcutaneous central venous catheter systems were used in paediatric oncology patients. Complications were few--namely, blockage and four infective episodes, all of which were successfully treated. Infective rate was 0.189 episodes per 100 days' use, which is substantially lower than that reported with other central venous catheters.

Antineoplastic Agents↗