Acute ataxia complicating Langerhans cell histiocytosis.
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Acute Disease↗
Biomedical subjects
J Pritchard
Publications and source records attributed to J Pritchard.
Apolipoprotein E genotypes and clinical outcome in Guillain-Barré syndrome.
BACKGROUND: Polymorphism of the gene encoding the cholesterol transport protein apolipoprotein E (APOE, gene; apoE, protein), known to be involved in axonal regeneration and remyelination, influences outcome after a variety of central nervous system disorders. Apolipoprotein E gene polymorphisms could affect recovery from Guillain-Barré syndrome. OBJECTIVE: To correlate APOE genotypes with residual disability and degree of improvement in Guillain-Barré syndrome, assessed one year after presentation METHODS: 91 patients with the syndrome were recruited from southeast England and their APOE genotypes were determined. RESULTS: There were no clear differences in APOE genotype or allele frequencies when comparing the 91 patients with controls, nor when comparing 81 patients with good outcome and 10 with poor outcome. CONCLUSIONS: APOE genotype did not influence susceptibility to Guillain-Barré syndrome or recovery from it. This may be because our sample size of 91 was not sufficiently large to detect small differences in recovery associated with different APOE genotypes, or because cholesterol transportation is not a crucial rate limiting step in peripheral nerve regeneration.
Adolescent↗
Sensitivity of cell hydraulic conductivity to mercury is coincident with symplasmic isolation and expression of plasmalemma aquaporin genes in growing maize roots.
Root elongation occurs as individual cells along the growing zone increase in volume. This increase is caused by water entering the cell either by moving across the cell membrane from the apoplast via aquaporins, or entering through plasmodesmata that symplastically connect cells to each other or with the sieve element. In this investigation we used mercury, a known inhibitor of aquaporin water channels, to manipulate the water permeability of growing maize root cells. 20 micro M HgCl(2) was found to reduce root elongation by around 75% and this reduction in growth was greatest in the older growing cells, with little effect on the younger cells near the root tip. Cell hydraulic conductivity (Lp) of cells close to the root tip (at 3 mm) remained unaffected by mercury treatment in contrast to older growing and non-growing cells where Lp was greatly reduced. Using reverse transcription-polymerase chain reaction analysis, younger root regions were shown to express higher levels of two plasmalemma intrinsic protein genes than older root regions further away from the root tip. However, a gene encoding a tonoplast aquaporin was expressed at similar levels in both regions of the growing zone. The fluorescent tracer, carboxyfluorescein, demonstrated symplastic connection between the phloem and root cortical cells at 3 mm but not at 5 or 20 mm. The data are consistent with a decrease in symplastic continuity along the growing zone and highlight a change in the principal pathway of water uptake during the development of the growing root cell.
Algorithms↗
Role of chest computed tomography at diagnosis in the management of Wilms' tumor: a study by the United Kingdom Children's Cancer Study Group.
PURPOSE: This study sought to determine whether the identification of minimal pulmonary metastatic disease by chest computed tomography (CT) performed at diagnosis in patients with Wilms' tumor and normal chest x-rays (CXR) could predict a subgroup of children at increased risk of pulmonary relapse. PATIENTS AND METHODS: A retrospective analysis was carried out of the records of 449 children entered onto the United Kingdom Childrens' Cancer Study Group Second Wilms' Tumor Study between July 1986 and September 1991. The imaging protocol did not stipulate chest CT at diagnosis, but 141 children who had normal frontal and lateral CXRs and a chest CT scan performed at diagnosis were eligible for analysis. After surgery, children with stage I Wilms' tumor received single-agent chemotherapy (vincristine), whereas children with stages II, III, and bilateral Wilms' tumor received combination chemotherapy. Most children with stage III tumors were also treated with abdominal radiotherapy (20 Gy). RESULTS: In 31 patients (22%), pulmonary nodules were visible on chest CT; eight experienced relapse, four (15%) in the lungs. When only stage I patients were analyzed, there was a significant difference between the pulmonary relapse rate of 43% (three of seven) in the CT-positive group and 10% (five of 48) in the CT-negative group (P =.02). Four of eight patients with stage I disease with pulmonary relapse died. CONCLUSION: CT seemed to identify a subgroup of stage I patients who were at increased risk of pulmonary relapse. These children had received only single-agent chemotherapy. A prospective randomized trial is needed to clarify whether these children would benefit from combination chemotherapy.
Antineoplastic Agents, Phytogenic↗
Hepatocellular carcinoma in children: results of the first prospective study of the International Society of Pediatric Oncology group.
PURPOSE: To improve survival and reduce operative morbidity and mortality in children with primary epithelial liver tumors by using preoperative chemotherapy, as well as to collect information on the epidemiology, natural history, and prognostic factors. PATIENTS AND METHODS: Forty children with hepatocellular carcinoma (HCC) were registered onto the Group for Epithelial Liver Tumors International Society of Pediatric Oncology's first study from January 1990 to February 1994. The outcome could be analyzed in 39 of those patients. Disease was often advanced at the time of diagnosis; metastases were identified in 31% of the children and extrahepatic tumor extension, vascular invasion, or both in 39%. Multifocal tumors were common (56%). Thirty-three percent of tumors were associated with hepatic cirrhosis. All but two patients received preoperative chemotherapy (cisplatin and doxorubicin). RESULTS: Partial response was observed in 18 (49%) of 37 patients; there was no response or progression in the remainder. Complete tumor resection was achieved in 14 patients (36%). Twenty patients (51%) never became operable. Overall survival at 5 years was 28%, and event-free survival was 17%. Most deaths resulted from tumor progression (26 of 28). Presence of metastases and pretreatment extent of disease system grouping at diagnosis had an adverse influence on overall survival in multivariate analysis. CONCLUSION: Survival for pediatric HCC patients is significantly inferior to that for children with hepatoblastoma. Complete tumor excision remains the only realistic chance of cure, although it is often prevented by advanced disease. The presence of metastases is the most potent predictor of poor prognosis. A prospective worldwide cooperation in the field of pediatric HCC should be encouraged to look for novel therapeutic concepts.
Adolescent↗
Risk of relapse of Guillain-Barré syndrome or chronic inflammatory demyelinating polyradiculoneuropathy following immunisation.
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Guillain-Barre Syndrome↗
NeuroD2 is necessary for development and survival of central nervous system neurons.
NeuroD2 is sufficient to induce cell cycle arrest and neurogenic differentiation in nonneuronal cells. To determine whether this bHLH transcription factor was necessary for normal brain development, we used homologous recombination to replace the neuroD2 coding region with a beta-galactosidase reporter gene. The neuroD2 gene expressed the reporter in a subset of neurons in the central nervous system, including in neurons of the neocortex and hippocampus and cerebellum. NeuroD2(-/-) mice showed normal development until about day P14, when they began exhibiting ataxia and failure to thrive. Brain areas that expressed neuroD2 were smaller than normal and showed higher rates of apoptosis. Cerebella of neuroD2-null mice expressed reduced levels of genes encoding proteins that support cerebellar granule cell survival, including brain-derived neurotrophic factor (BDNF). Decreased levels of BDNF and higher rates of apoptosis in cerebellar granule cells of neuroD2(-/-) mice indicate that neuroD2 is necessary for the survival of specific populations of central nervous system neurons in addition to its known effects on cell cycle regulation and neuronal differentiation.
Animals↗
Ascertainment of the incidence of Beckwith-Wiedemann syndrome in the National Wilms Tumor Study Group.
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Beckwith-Wiedemann Syndrome↗
Late relapse and prognosis for neuroblastoma patients surviving 5 years or more: a report from the European Neuroblastoma Study Group "Survey".
BACKGROUND AND PROCEDURE: Most deaths from neuroblastoma occur within 2 years of diagnosis but there have been several anecdotal reports of relapse and death after much longer periods of follow up. In order to investigate and quantify the risk of late events we analysed data for patients registered with the European Neuroblastoma Study Group between 1982 and 1990. Out of a total of 1,277 children registered, 427 were alive with follow-up beyond 5 years from diagnosis (median follow-up of 8.8 years, range 5-14 years). Of these 406 were in remission with no prior recurrence, 16 were in remission having experienced a relapse prior to 5 years, and 5 were alive with progressive disease. RESULTS: For the 406 patients in remission with no prior relapse the 10 year progression free survival (PFS) was 96% (CI 94-98). For those aged over 1 year with stage 4 disease at diagnosis 10 year PFS was 88% (CI 79-96) compared to 98% (CI 97-99) for other patients combined, P< 0.001. In a multivariate analysis of all 422 patients in remission at 5 years, significant risk factors for subsequent relapse were age > 1 yr with stage 4 disease at diagnosis (relative risk 10.5, P < 0.001) and prior relapse (RR 4.2, P= 0.01). CONCLUSIONS: The results of this study emphasise the importance of longterm follow-up of patients and the need for late monitoring of clinical trials in children with neuroblastoma. They also provide a baseline for comparison with future and hopefully more effective treatment programmes.
Abdominal Neoplasms↗
Lactose as a carrier in dry powder formulations: the influence of surface characteristics on drug delivery.
The aim of the study was to investigate the interdependence of carrier particle size, surface treatment of the carrier, and inclusion of fines on the drug delivery from dry power inhaler formulations. Two size fractions (< 63 and 63-90 microm) of alpha-lactose monohydrate were subjected to treatment with 95% (v/v) ethanol to introduce small asperities or cavities onto the otherwise smooth surface without substantially changing the particle shape. After blending with albuterol sulfate [ALB; volume median diameter (VMD), 1.9 microm; geometric standard deviation (GSD), 1.5], the solvent-treated lactose produced a fine particle fraction (FPF; < 6.18 microm) and dispersibility of the drug that was significantly (ANOVA p < 0.01) lower than that which resulted from formulations containing untreated lactose of a similar size fraction, after aerosolization at 60 L min(-1) via a Rotahaler. The two size fractions of the treated lactose resulted in similar deposition profiles of ALB. The effects of such surface asperities or cavities of lactose were offset by introducing a small amount (5% w/w) of smaller-sized lactose (5-10 microm) to the powder formulations. The fine lactose increased the FPF and dispersibility of ALB to such a level that all lactose batches, regardless of particle size or whether solvent treated, produced a similar fraction of aerosolized ALB. The inclusion of recrystallized needle lactose (5-15 microm) was superior to micronized lactose in improving the aerosolization of ALB. The findings of this study indicate that the presence and characteristics of the finer fraction of lactose carrier particles dominate over the particle size and surface smoothness of the carrier particles in determining dispersion and deaggregation of drugs from dry powder formulations for inhalation.
Chemistry, Pharmaceutical↗
Double-blind randomized phase II study of hyperbaric oxygen in patients with radiation-induced brachial plexopathy.
BACKGROUND: Radiation-induced brachial plexopathy (RIBP) is an untreatable complication of curative radiotherapy for early breast cancer, characterized by chronic neuropathic pain and limb paralysis. Hyperbaric oxygen (HBO2) therapy is known to promote healing of tissue rendered ischaemic by radiotherapy, but is untested in RIBP. METHODS: Thirty four eligible research volunteers suffering from RIBP were randomized to HBO2 or control group. The HBO2 group breathed 100% oxygen for 100 min in a multiplace hyperbaric chamber on 30 occasions over a period of 6 weeks. The control group accompanied the HBO2 group and breathed a gas mixture equivalent to breathing 100% oxygen at surface pressure. All volunteers and investigators, except the operators of the hyperbaric chamber and the trial statistician, were blind to treatment assignments. The warm sensory threshold, which measures the function of small sensory fibres, was selected as the primary endpoint. FINDINGS: Pre-treatment neurophysiological tests were grossly abnormal in the affected hand compared to the unaffected hand in both HBO2 and control groups, as expected, but no statistically significant differences were noted in either group at any time up to 12 months post-treatment. However, normalization of the warm sensory threshold in two of the HBO2 group was reliably recorded. Two cases with marked chronic arm lymphoedema reported major and persistent improvements in arm volume for at least 12 months after treatment with HBO2. IINTERPRETATION: There is no reliable evidence to support the hypothesis that HBO2 therapy slows or reverses RIBP in a substantial proportion of affected individuals, although improvements in warm sensory threshold offer some suggestion of therapeutic effect. Improvement in long-standing arm lymphoedema was not anticipated, and justifies further investigation.
Action Potentials↗
Problems in the imaging of three common paediatric solid tumours.
Modern radiologic techniques have led to a more accurate diagnosis and staging in many paediatric malignancies. The optimal imaging of some tumours is not, however, well defined and needs to be constantly re-assessed. Similarly with evolving clinical treatment protocols, recommended imaging strategies should be continually re-evaluated. The significance of some findings on radiologic examinations in paediatric oncology patients is disputed. A number of issues relating to the imaging of Wilms', neuroblastoma and rhabdomyosarcoma in childhood are discussed.
Biopsy↗
The use of lactose recrystallised from carbopol gels as a carrier for aerosolised salbutamol sulphate.
Lactose was crystallised either from Carbopol gel without stirring or from a constantly-stirred aqueous solution, to obtain lactose crystals designated as Carbo and control lactose, respectively. The Carbo lactose was shown to have a more regular shape with smoother surface as compared with the control lactose. These lactoses were fractionated by sieving to produce batches with different sizes before blending separately with salbutamol sulphate (SS, VMD 5.8 microm) in a ratio of 67.5:1 w/w using the same mixing procedure. SS dispersion and deaggregation were investigated using a 4-stage liquid impinger after aerosolisation at 28.3, 60.0 and 96.0 l/min via a Rotahaler. At all flow rates, the Carbo lactose produced significantly higher (ANOVA, P<0.01) emission of SS from the Rotahaler as compared with the control lactose of a similar size. The Carbo lactose also resulted in a significantly (P<0.05) higher fine particle fraction of SS than the control lactose. Moreover, drug emission from formulations containing the Carbo lactose was consistently more reproducible than those of the control lactose blends. In conclusion, the efficiency and reproducibility of drug delivery by dry powder inhalers can be improved using carrier particles of precisely defined morphological features.
Acrylic Resins↗
Veno-occlusive disease with multi-organ involvement following actinomycin-D.
Actinomycin-D (Act-D) is a rare cause of veno-occlusive disease (VOD). Between 1993 and 1998, we managed 6 patients, all male, median age 19 months (range 6-48 months) who received Act-D for Wilms' tumour (n=4), clear cell sarcoma (n=1) or rhabdomyosarcoma (n=1). VOD presented with a median platelet count of 12 x 10(9)/l, INR 3.8, fibrinogen 16 mg/l, fibrinogen degradation products (FDPs) > or =80 microg/l, aspartate aminotransferase (AST) 6922 IU/l, bilirubin 47 micromol/l. In 3 cases, transient liver dysfunction and thrombocytopenia without neutropenia had been observed after a previous course of Act-D. All six children developed encephalopathy, hepatomegaly, ascites, reversed portal flow and renal impairment. All received mechanical ventilation and two required haemofiltration. The treatment was supportive. Severe Adult Respiratory Distress Syndrome developed in 3 patients, all of whom died. 3 patients recovered. The outcome of VOD with multi-organ failure is poor. Intravascular coagulopathy precedes and characterises severe VOD during Act-D treatment.
Antibiotics, Antineoplastic↗
Monthly docetaxel and weekly gemcitabine in metastatic breast cancer: a phase II trial.
BACKGROUND: Docetaxel and gemcitabine are active against breast cancer. The purpose of this phase II study was to evaluate the efficacy and safety of monthly docetaxel combined with weekly gemcitabine in patients with chemotherapy-pretreated metastatic breast cancer. PATIENTS AND METHODS: Thirty-nine patients were enrolled, of whom thirty had received prior chemotherapy in the adjuvant setting, seven for metastatic disease, and two for both, including prior anthracycline in 33 patients. Treatment was gemcitabine 800 mg/m2 days 1, 8, 15 and docetaxel 100 mg/M2 on day 1, with cycles repeated every four weeks. RESULTS: Response rate was 79% (95% confidence interval (CI): 63%-91%), with 2 complete and 29 partial responses. Twenty-five of the responders remained progression-free for more than six months. Median survival was 24.5 months. Delivered dose intensity of gemcitabine was lower than expected (63% of planned). The predominant hematologic toxicity was grade 4 neutropenia in 36 patients, complicated by fever in three patients. With the exception of asthenia, severe non-hematological toxicities were infrequent. CONCLUSIONS: Monthly docetaxel, combined with weekly gemcitabine, has significant but manageable hematologic toxicity. Despite frequent dose adjustments, this doublet is very active in metastatic breast cancer, producing a high proportion of durable responses associated with favorable survival.
Adult↗
Juvenile xanthogranuloma as a sequel to Langerhans cell histiocytosis: a report of three cases.
We report three children who had multisystem Langerhans cell histiocytosis (LCH) with cutaneous involvement and subsequently developed juvenile xanthogranuloma (JXG). JXG appeared 3--6 years after the initial manifestation of LCH. JXG lesions, which presented as yellowish papules, revealed typical Touton giant cells and were factor XIIIa positive but S100 and CD1a negative. Non-LCH histiocyte disorders, such as JXG, are known to occur as a reaction to a variety of external stimuli such as infection and trauma. It is therefore conceivable that the inflammatory reaction associated with LCH may have precipitated the development of JXG in our patients. Alternatively, one could speculate that this association might be due to a common histogenetic precursor of the cell types involved.
Child↗
A randomized trial of treatment for multisystem Langerhans' cell histiocytosis.
OBJECTIVE: To compare 2 active agents, vinblastine and etoposide, in the treatment of multisystem Langerhans' cell histiocytosis (LCH) in an international randomized study. STUDY DESIGN: One hundred forty-three untreated patients were randomly assigned to receive 24 weeks of vinblastine (6 mg/m(2), given intravenously every week) or etoposide (150 mg/m(2)/d, given intravenously for 3 days every 3 weeks), and a single initial dose of corticosteroids. RESULTS: Vinblastine and etoposide were equivalent (P > or = .2) in all respects: response at week 6 (57% and 49%); response at the last evaluation (58% and 69%); toxicity (47% and 58%); and probability of survival (76% and 83%) [corrected], of disease reactivation (61% and 55%), and of developing permanent consequences (39% and 51%) including diabetes insipidus (22% and 23%). LCH reactivations were usually mild, as was toxicity. All children > or = 2 years old without risk organ involvement (liver, lungs, hematopoietic system, or spleen) survived. With such involvement, lack of rapid (within 6 weeks) response was identified as a new prognostic indicator, predicting a high (66%) mortality rate. CONCLUSIONS: Vinblastine and etoposide, with one dose of corticosteroids, are equally effective treatments for multisystem LCH, but patients who do not respond within 6 weeks are at increased risk for treatment failure and may require different therapy.
Adolescent↗
Interferon-gamma receptor deficiency mimicking Langerhans' cell histiocytosis.
Two patients who were initially given a diagnosis of Langerhans' cell histiocytosis on the basis of the clinical, radiologic, and biopsy findings had mycobacterial infection subsequently identified. The correct diagnosis of dominant partial interferon-gamma receptor deficiency was established.
BCG Vaccine↗