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J Pritchard

Publications and source records attributed to J Pritchard.

At least 55 records · Page 3Linked to original sources
PubMed2000

Cisplatin, doxorubicin, and delayed surgery for childhood hepatoblastoma: a successful approach--results of the first prospective study of the International Society of Pediatric Oncology.

PURPOSE: Hepatoblastoma (HB) is a rare malignant liver tumor which occurs almost exclusively in childhood. In the 1970s, survival was approximately 20% to 30%. Since the introduction of cisplatin (PLA) and doxorubicin (DO) into the chemotherapy regimens used to treat these patients, the survival rate has improved dramatically. In most recent studies, primary surgery preceded chemotherapy. In this study by the liver group of the International Society of Pediatric Oncology the aim was to improve survival and reduce operative morbidity and mortality by using preoperative chemotherapy. PATIENTS AND METHODS: After biopsy and assessment of pretreatment extent of disease all patients were treated with continuous 24-hour intravenous infusion of PLA 80 mg/m(2) followed by DO 60 mg/m(2) over 48 hours (PLADO). After four courses of this chemotherapy, patients were reassessed. Where possible, the primary tumor was resected and treatment completed with two more courses of chemotherapy. RESULTS: One hundred fifty-four patients were registered in the study, and 138 received preoperative chemotherapy. One hundred thirteen (82%) showed a partial response with tumor shrinkage and serial decrease of serum alpha-fetoprotein levels. One hundred fifteen patients had delayed surgery, and 106 (including six with liver transplants) had complete resection of primary tumor. Five-year event-free survival was 66%, and overall survival was 75%. CONCLUSION: This study demonstrates that international collaboration on a large scale is feasible. The toxicity of chemotherapy and morbidity of surgery were acceptable and the overall survival gratifyingly high. We now regard PLADO chemotherapy and delayed surgery to be the best available treatment for children with HB. Other treatment programs should be measured against this standard.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Hepatoblastoma presenting with lung metastases: treatment results of the first cooperative, prospective study of the International Society of Paediatric Oncology on childhood liver tumors.

BACKGROUND: The prognosis of children who are affected by hepatoblastoma (HB) that presents with lung metastases has always been considered very poor. In light of the overall improvement in the survival of HB patients since the introduction of cisplatin (CDDP) in the therapeutic armament of this tumor, the question has been raised whether patients with metastatic HB also would benefit from this drug. The purpose of the current study was to address this issue by analyzing the treatment outcome of those patients presenting with metastases who entered into the first HB study on childhood liver tumors conducted by the International Society of Paediatric Oncology (SIOPEL 1). METHODS: SIOPEL 1 was a prospective, international, multicentric, single-arm study based on preoperative chemotherapy that was open to patient registration from January 1990 to February 1994. After undergoing a biopsy, patients received four courses of CDDP (80 mg/m(2) in a 24-hour, continuous infusion) on Day 1 followed by doxorubicin (60 mg/m(2) in a 48-hour, continuous infusion) on Days 2 and 3 (PLADO). Surgery was performed after four courses of PLADO and was followed by two more courses. Untreated children age < 16 years with biopsy-proven HB were eligible for the study. Metastatic spread was assessed by chest X-ray and, where available, lung computed tomography scan. RESULTS: Thirty-one of 154 children that entered into the trial presented with metastases. Eight children presently are alive with no evidence of disease (NED) after being treated with protocol therapy only (median follow-up, 60 months); nine children are alive with NED after having failed PLADO and having been rescued with alternative therapies (median follow-up, 80 months). The 5-year overall and event free survival rates for these children were 57% (95% confidence interval, 39-75%) and 28% (95% confidence interval, 12-44%), respectively. Persistent lung disease was the main reason for PLADO failure (17 of 23 patients; 74%). CONCLUSIONS: The SIOPEL 1 therapeutic strategy seems to cure 25% of the HB patients who present with metastases. However, further chemotherapy and the use of thoracotomies still can save significant numbers of these children.

Adolescent↗
PubMed2000

Recurrence of Langerhans cell histiocytosis in the graft after pediatric liver transplantation.

Two girls were diagnosed with Langerhans cell histiocytosis (LCH) at the age of 16 and 7 months and developed end stage chronic liver disease related to LCH-induced sclerosing cholangitis at 28 and 8 months, respectively. They received liver transplants at 34 and 14 months of age. Five months post-orthotopic liver transplantation (OLT) one of the patients developed posttransplant lymphoproliferative disease, successfully treated with a combination of surgery and reduction of immunosuppression. Fourteen months post-OLT she developed diabetes insipidus, bilateral ear discharge, and new osteolytic lesions. After transplantation both girls had mild skin reactivations of LCH, requiring minimal steroid increments. At 60 and 5 months post-OLT intrahepatic LCH recurrence was diagnosed on the basis of abnormal biliary enzymes and presence of Langerhans cells in the grafts. Initial cholangiography in both patients was unremarkable. LCH activity was controlled by maintenance chemotherapy with vinblastine, etoposide, and prednisolone. Ten months after reappearance of LCH in the liver graft a follow-up cholangiography in one of the girls demonstrated a low grade cholangiopathy. Residual elevation of liver enzymes probably represents an ongoing pathogenic process.

Cholangiography↗
PubMed2000

The influence of carrier morphology on drug delivery by dry powder inhalers.

Alpha-lactose monohydrate was prepared to have different morphological features but with similar particle size. The crystal shape and surface smoothness of lactose were quantified by a number of shape descriptors and these were supported qualitatively by the visual examination of scanning electron (SE) micrographs of the crystals. All batches of lactose were subjected to a similar history of processing before blending separately with micronised salbutamol sulphate (SS) in a ratio of 67.5:1, w/w, using similar procedures. In vitro deposition of SS from these formulations was investigated after aerosolisation of the formulations at 60 l min(-1) via the Rotahaler and the Cyclohaler into a twin stage liquid impinger. The formulations prepared using the different batches of lactose produced different deposition profiles of SS. The fine particle (< 6.4 microm) fraction (FPF) of aerosolised SS varied from 12.6 +/- 2.4 to 25.6 +/- 1.5% after aerosolisation from the Cyclohaler whilst it changed from 15.0 +/- 2.2 to 24.4 +/- 0.8% after aerosolisation from the Rotahaler. The fine particle dose (FPD) and dispersibility of SS followed a similar trend to the change in the FPF of the drug. No significant difference (ANOVA P > 0.05) was observed for the deposition profiles of SS after aerosolisation from the Rotahaler and the Cyclohaler. The FPF and dispersibility of SS increased with either the surface smoothness (P < 0.01) or elongation ratio (P < 0.01) of lactose crystals. The t-ratio values of FPF and dispersibility of SS generated by changes in the surface smoothness were similar to those resulting from changes in elongation ratio. Increasing either the surface smoothness or the elongation ratio of lactose crystals will increase the potentially respirable fraction of SS from dry powder formulations for inhalation.

Administration, Inhalation↗
PubMed2000

Clinical prognostic factors in 1277 patients with neuroblastoma: results of The European Neuroblastoma Study Group 'Survey' 1982-1992.

In 1982 the European Neuroblastoma Study Group (ENSG) established a prospective registry for patients with newly diagnosed neuroblastoma ('The ENSG Survey'). Clinical information was collected primarily to: (a) establish an ENSG database; and (b) investigate prognostic factors in neuroblastoma. This paper summarises the results of the survey. By 1992, 1277 patients with a median age of 26 months (range: 0-289 months), gender ratio of 1.19 M:F had been registered from 30 centres. The median follow-up of survivors is 9.7 years (range: 1-14 years). Overall 5-year survival (S) is 45% (95% CI 42-48%), and event-free survival (EFS) is 43% (95% CI 40-45%). For both survival and EFS the key established prognostic factors, stage and age, are highly significant (P<0.001). In particular, patients under 1 year of age at diagnosis, whatever the disease stage, had a more favourable prognosis than older patients; stage 2 (EFS 93% (95% (CI 85-97) versus 76% (95% CI 67-86), P=0.02), stage 3 (EFS 91% (95% CI 82-96) versus 52% (95% CI 44-60), P<0.001) and stage 4 (EFS 59% (95% CI 48-69) versus 16% (95% CI 13-19), P<0.001). Multivariate analysis established that the anatomical location of the primary tumour (i.e. abdominal versus other sites) and primary tumour volume also conferred a statistically significant difference. In stage 4 disease the 20% of patients without demonstrable bone marrow involvement had a more favourable prognosis than those with infiltrated marrow (EFS 36% (95% CI 13-19) versus 16% (95% CI 29-45), P<0.001). Urine catecholamine metabolite levels (raised versus normal), histology (ganglioneuroblastoma versus neuroblastoma) and gender had no significant effect on outcome after stage and age were accounted for. 5-year survival following first relapse is only 5.6% (95% CI 2.8-8.4). This ENSG Survey provides secure data for future comparisons with new prognostic factors and treatment programmes.

Adolescent↗
PubMed2000

Pretreatment prognostic factors for children with hepatoblastoma-- results from the International Society of Paediatric Oncology (SIOP) study SIOPEL 1.

The aim of this study was to investigate the prognostic significance of pretreatment patient and tumour characteristics for overall (OS) and event-free (EFS) survival in 154 children affected by hepatoblastoma (HB) in the first prospective liver tumour study run by the International Society of Paediatric Oncology. The pretreatment characteristics studied were age, alpha-fetoprotein, platelet count, histology; from radiology: intrahepatic tumour extension (PRETEXT), lung metastases, enlarged hilar lymph nodes, vena cava or extrahepatic vena porta tumour extension and tumour focality. Five-year OS was 75% (95% confidence interval (CI) 68-82%) and EFS 66% (95% CI 59-74%). Both were univariately associated with PRETEXT and the presence of metastases. Additionally tumour focality and enlargement of hilar lymph nodes at diagnosis were univariately associated with EFS. In multivariate analysis, PRETEXT was the only predictor of OS; PRETEXT and metastases were predictors of EFS. There is a need to investigate further these factors to confirm their validity.

Adolescent↗
PubMed2000

Crystallization of lactose from carbopol gels.

PURPOSE: To crystallize lactose under static conditions with a view to preparing crystals of well-defined morphology. METHODS: et-Lactose monohydrate was crystallized from neutralized Carbopol 934 gels. When the majority of crystals had grown to maturity, the gels were acidified using diluted hydrochloric acid and the crystals were harvested by filtration or centrifugation and washed with ethanol-water mixtures. RESULTS: Crystals prepared from the gel had a consistently narrower size distribution than control crystals, prepared from solution under constant stirring. If crystallization was effected in the gel without sedimentation of the crystals, then the resultant crystals had smooth surfaces without visually detectable surface roughness or asperities viewed by optical microscopy. The crystals from Carbopol gels also exhibited the uniform shape of an elongated tomahawk regardless of the crystallization conditions, in contrast to crystallization under constant stirring, where the crystal shape of lactose changed with crystallization conditions especially as a function of the initial concentration of lactose. All batches of lactose crystals prepared from Carbopol gels existed as alpha-lactose monohydrate, which showed better flowability than the controls of a similar particle size. CONCLUSIONS: Crystallization from Carbopol gel produces lactose crystals of uniform size, regular shape, smooth surface, and improved flowability.

Acrylic Resins↗
PubMed2000

Growth and endocrine disorders in multisystem Langerhans' cell histiocytosis.

INTRODUCTION: Langerhans' cell histiocytosis is a rare disorder, with diabetes insipidus occurring in up to half of patients. Causes of growth failure include the illness itself, treatments used and growth hormone insufficiency. PATIENTS AND METHODS: We identified all patients with an endocrinopathy secondary to Langerhans' cell histiocytosis (LCH). Growth data were analysed from all patients with multisystem involvement. RESULTS: Of 144 patients with multisystem LCH, 50 had an endocrinopathy, 49 of whom had diabetes insipidus. Growth hormone insufficiency (GHI) was present in 21 patients, seven of whom had other anterior pituitary deficiencies as well (gonadotrophin deficiency + GHI n = 2, gonadotrophin deficiency + TSH deficiency + GHI n = 2, panhypopituitarism n = 3). GH insufficiency, the development of which appeared to be independent of pituitary radiation, occurred at a median age of 8.3 years (4.7-18 years) and at a median interval of 3.5 years (0-11.8 years) after diagnosis of LCH. The median height SDS at diagnosis of growth hormone insufficiency was -2.9. Thirteen of the patients with growth hormone insufficiency attained final height with a median height SDS of -1.2. The final height SDS of 15 patients without GH insufficiency was closer to target height SDS, but not statistically different from that of the GH insufficient group. CONCLUSIONS: GH therapy significantly improves growth in GH insufficient patients with Langerhans' cell histiocytosis. Early institution of GH therapy may further improve height outcome. However, most children with Langerhans' cell histiocytosis regardless of endocrine function, failed to reach target height.

Adolescent↗
PubMed2000

Pelvic neuroblastoma: low mortality and high morbidity.

BACKGROUND/PURPOSE: Cervical, thoracic, and pelvic neuroblastomas are regarded as having a better outcome than abdominal primaries. The aim of the study was to analyze the results of treatment of pelvic neuroblastomas in our institution. METHODS: The authors reviewed the records of 284 patients with neuroblastoma treated in our hospital during the period 1983 through 1998 and identified 17 (6%) with pelvic tumors. The revised International Neuroblastoma Staging System was used. RESULTS: There were 6 patients with stage 1 disease, 8 with stage 2, 2 with stage 3, and 1 with stage 4 disease. Intraspinal extension of the tumor was present in 7 patients (41%). Except for one child with stage 4 disease, all patients underwent an attempt of tumor excision, and 6 had a complete resection. All 7 patients with intraspinal tumor survived. Permanent postoperative neurological complications occurred in 6 patients (35%). These included sciatic nerve palsy, urinary and fecal incontinence, neuropathic bladder, and leg weakness or nerve root injury L4-S1. Three of 17 patients died, but 1 fatality was unrelated to the tumor. The overall survival rate was 82% and was not influenced by the completeness of tumor resection. CONCLUSIONS: The survival of nonmetastatic pelvic neuroblastoma in our institution is good despite incomplete tumor resection. Intraspinal extension is not a negative prognostic factor. Considering the high incidence of permanent neurological damage after surgery and the generally favorable biological characteristics of these tumors, surgical treatment should not be overaggressive.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

The treatment of Wilms' tumour: results of the United Kingdom Children's cancer study group (UKCCSG) second Wilms' tumour study.

The aims of the UKW2 study were: (1) to further refine treatment for stage I and II favourable histology (FH) patients; (2) to consolidate the UKW1 results for stage III FH patients; (3) to improve the outlook for patients with inoperable primary tumours and those patients with stage IV and unfavourable histology disease. Treatment consisted of primary nephrectomy, wherever possible, followed by chemotherapy and radiotherapy, as dictated by stage and histology. Treatment was refined successfully for stage I and II FH patients. The 4-year event-free survival for these two groups was 94% and 91%, respectively. Stage III FH patients had a 4-year event free survival of 84%. The outlook for patients with clear cell sarcoma of the kidney is as good as for patients with favourable histology, whilst that for patients with anaplastic or rhabdoid variants remains poor. The outlook for the majority of children with Wilms' tumour is now excellent.

Adolescent↗
PubMed2000

Long term follow up of topical mustine treatment for cutaneous langerhans cell histiocytosis.

BACKGROUND AND OBJECTIVES: Skin lesions in Langerhans cell histiocytosis (LCH) are often painful and difficult to treat. Topical application of nitrogen mustard (0.02% mechlorethamine hydrochloride, mustine), an alkylating cytostatic agent, has been shown to be effective. There is, however, concern about potentially harmful long term side effects. STUDY DESIGN: In a retrospective study 20 children with LCH (average extent of initial skin involvement: 16.4% body surface) were followed up for an average of 8.3 years after completion of topical mustine therapy. They had received a total of 34 courses (mean duration 14.2 weeks) of topical mustine. Disease status on follow up was assessed according to the Histiocyte Society classification. RESULTS: After mustine was introduced, 16 patients were able to discontinue systemic steroids and/or chemotherapy. Topical mustine was well tolerated in 18 patients, but two developed irritant dermatitis. On follow up, the disease was inactive in 10 patients. Among the children with active disease, six had mild skin disease and four had progressive disease, two of them with skin lesions unresponsive to mustine treatment. Scars confined to areas of formerly active skin disease were found in six patients. There was no evidence of premalignant or malignant skin disease in the treated areas. CONCLUSION: Topical mustine is an effective and safe treatment for skin disease in most children with LCH. Residual scarring was probably a result of the disease itself rather than to mustine. Although no evidence of skin cancer was found in this study, continued long term follow up is advisable.

Administration, Topical↗
PubMed2000

Motor neuron disease--a review.

It is now clear that patients with MND are best managed using a multi-disciplinary approach conforming to evidence-based guidelines. Whilst scientific advances into the aetiology of MND have been of great importance in both the understanding of this and other neurodegenerative disease, they have only recently led to therapy directed at disease progression. The management of patients with MND remains largely supportive but it is hoped that the future may hold better prospects for those with the disease.

Adult↗
PubMed2000

The influence of crystallization conditions on the morphology of lactose intended for use as a carrier for dry powder aerosols.

Lactose has been widely used as a carrier for inhalation aerosols. The carrier morphology is believed to affect the delivery of the drug. The aim of this study was to investigate the effects of crystallization conditions on the morphology of alpha-lactose monohydrate intended for use as the carrier for dry powder aerosols. The crystallization of lactose was carried out from aqueous solutions at different supersaturations, temperatures, different stages of crystallization and in the presence of different water-miscible organic solvents. The majority of lactose crystals were found to be either tomahawk-shaped or pyramidal after crystallization at an initial lactose concentration between 33-43% w/w, but these became prismatic if the lactose concentration was increased to 50% w/w. A further increase in the lactose concentration to 60% w/w led to the preparation of elongated cuboidal crystals. Higher initial lactose concentrations tended to result in the crystallization of more elongated particles. Crystallization at 40 degrees C was shown to prepare lactose crystals with a more regular shape and a smoother surface than those crystallized at 0 degrees C. Lactose particles generated during the later stage of crystallization were found to be more regular in shape with a smoother surface than those prepared in the earlier stage. The addition of 10% (v/v) methanol or ethanol or acetone to the mother liquor increased the growth rate of lactose particles whereas addition of propanol or glycerine inhibited the rate of crystal growth. Lactose crystals prepared in the presence of glycerine were more regularly shaped with a smoother surface than those prepared in the presence of ethanol or acetone. All the resultant crystals were shown to comprise alpha-lactose monohydrate. Lactose crystals could be prepared with a precisely defined morphology by means of carefully controlling the crystallization conditions.

Aerosols↗
PubMed2000

The effects of carrier size and morphology on the dispersion of salbutamol sulphate after aerosolization at different flow rates.

We have investigated the interdependence of various factors (particle size, surface smoothness, carrier particle shape, inhalation flow rate) on the deposition of a model drug (salbutamol sulphate) after aerosolization from a model inhaler device (Rotahaler). Different batches of alpha-lactose monohydrate were prepared to have different particle size, particle shape and surface smoothness. Each batch of lactose was then mixed separately with salbutamol sulphate in a ratio of 67.5 : 1 (w/w), under similar conditions. Drug deposition from each formulation was investigated using a 4-stage liquid impinger after aerosolization at 28.3, 60.0 and 96.0 L min(-1) via a Rotahaler. At a flow rate of 28.3 L min(-1), a large portion of drug particles was not emitted from the inhaler, the % emission varying from 29.6% to 66.6% for all formulations investigated. Drug emission tended to increase with particle size of the carrier whilst fine particle fraction, fine particle dose and dispersibility appeared to increase with decreasing particle size but increasing elongation ratio of the carrier particles. Increasing the flow rate to 60.0 L min(-1) was shown to increase drug emission since > 75% total dose was found to be emitted from the inhaler. Again, smaller or more elongated lactose particles resulted in a higher fine particle dose or fine particle fraction of salbutamol sulphate than the coarser carrier, although they produced a similar (analysis of variance P > 0.05) drug emission. Increasing the flow rate to 96.0 L min(-1) did not increase drug emission. Increasing the flow rate resulted in an increase in the fine particle fraction and fine particle dose of salbutamol sulphate from all formulations. The flow rate of the airstream appeared to play the most important role, followed by particle size and elongation ratio of the carrier particles, with the surface smoothness relatively less significant in determining the deposition of salbutamol sulphate from the Rotahaler.

Aerosol Propellants↗
PubMed2000

Novel therapeutic approaches to Guillain-Barré syndrome.

Guillain-Barré syndrome is an autoimmune disease which occurs throughout the world. Whilst the majority of patients can expect a reasonable recovery, about 10% die and 10% are left disabled with current therapy. The standard treatment is a five day course of iv. immunoglobulin, given at a dose of 0.4 g/kg/day, with plasma exchange as an equally efficacious alternative. Steroids are ineffective in Guillain-Barré syndrome. All new potential therapeutic agents need to be tested in addition to the standard agents available. Future potential therapies are suggested by the study of the animal model experimental autoimmune neuritis in the Lewis rat. Whilst in theory it is possible to target the different stages of the immune response, in practice not all of the steps at which experimental autoimmune neuritis can be prevented will be translatable to human Guillain-Barré syndrome. This is because Guillain-Barré syndrome probably presents after the immune reaction has been ongoing for some time and therefore early aspects of the immune response cannot be prevented. Many of the possible measures would have widespread immunosuppressive effects which would be unacceptable to patients. Interfering with the immune response by attempting to block antigen binding or inducing tolerance may not be practical, owing to the possibility of exacerbating disease. Once we have a more thorough understanding of the pathogenesis of Guillain-Barré syndrome, then immune-specific therapy for Guillain-Barré syndrome may become a possibility, rather than general immunosuppressive measures. Trials of beta-interferon and of a combination of steroid and i.v. immunoglobulin are underway. A trial of a second course of i.v. immunoglobulin is planned.

Adjuvants, Immunologic↗