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Biomedical subjects

R Hobson

Publications and source records attributed to R Hobson.

At least 19 recordsLinked to original sources

Anaplastic large cell lymphoma of bone--is it a bad tumor?

A teenage boy presented with a CD30-positive anaplastic large cell lymphoma (ALCL) affecting his scapula and was successfully treated with chemotherapy. His clinical features and outcome were compared with other cases described in the literature. A further review of 11 ALCL cases with bony involvement treated in the UK since 1990, including two with primary bone disease, did not suggest an unfavorable treatment outcome. This finding will need to be confirmed by further study on a larger patient cohort with primary bone ALCL.

Activin Receptors, Type II↗

Endometrial safety, overall safety and tolerability of transdermal continuous combined hormone replacement therapy over 96 weeks: a randomized open-label study.

OBJECTIVES: To establish whether transdermal continuous hormone replacement therapy (HRT) with estrogen/progestogen provides adequate long-term endometrial protection in postmenopausal women over a period of 96 weeks. METHODS: This multicenter, randomized, open-label, parallel-group study evaluated the endometrial effects and overall safety and tolerability of a transdermal matrix patch delivering estradiol (E2) 50 microg/day and norethisterone acetate (NETA) 140 microg/day (Estalis; patches applied twice weekly without intermediate breaks) and a once-daily oral comparator (Kliogest; one tablet containing E2 2 mg/NETA 1 mg) in postmenopausal women. A total of 406 women with an intact uterus, aged 44-69 years, were randomized in the 48-week core phase of the study, and 239 continued into the 48-week extension phase. Subjects were randomized in the ratio 3 : 1 to transdermal or oral E2/NETA treatment. RESULTS: No cases of endometrial hyperplasia or endometrial cancer were reported with either treatment during the core or extension phase. Both treatments were generally well tolerated, with most adverse events (>90%) being mild to moderate, although minor differences in the tolerability profile were observed between treatments. CONCLUSIONS: Continuous combined transdermal HRT with E2/NETA shows no evidence of an increased endometrial hyperplasia or endometrial cancer risk over a 96-week period.

Administration, Cutaneous↗

'Schools without walls?' Developments and challenges in dental outreach teaching - report of a recent symposium.

During the 2004 annual meeting of the International Association for Dental Research, the Education Research Group held a symposium on dental outreach teaching. After a brief introduction, which reviews relevant aspects of the relatively sparse literature, this paper summarises the proceedings, the themes and conclusions that emerged and the research issues that were identified. It aims to describe aspects of current practice around the world and to promote future discussion. Presenters gave details of outreach programmes for dental undergraduates in Australia, Finland, Malaysia (and Southeast Asia), the United Kingdom and the United States. From these presentations four themes emerged. They were: reasons for the introduction of outreach teaching, its perceived beneficial effects, organisational issues, educational issues. The reasons included a recognition of the need to educate dental undergraduates as members of 'care teams' in the environments and communities where they were ultimately like to work and the current shortage of both suitable patients and teachers (faculty) in many dental schools. A wide range of potential benefits and some disadvantages were identified. The organisational issues were, in the main, seen to relate to finance and administration. The educational issues included the need to train and monitor the performance of teachers at outreach clinics and to assess the performance of the undergraduates whilst at the outreach locations. It was concluded that new technology made it easier to teach at a distance and it was possible to create a dental 'school without walls'. It was recognised that few evaluations of dental outreach teaching have been carried out and that there were many research questions to be answered, including: whether it should be a voluntary or compulsory part of the undergraduate curriculum, how long it should last and what type of outcomes should be assessed.

Asia, Southeastern↗

Acute neurotoxicity in children with advanced stage B-non-Hodgkin's lymphoma and B-acute lymphoblastic leukaemia treated with the United Kingdom children cancer study group 9002/9003 protocols.

We reviewed the pattern of acute neurotoxicity in children with B-non-Hodgkin's lymphoma (B-NHL) and B-acute lymphoblastic leukaemia (ALL) treated with the UKCCSG 9002/9003 protocols. Among 175 patients, 21 (12%) developed acute neurotoxicity: 9002 protocol (n=11/112) and 9003 (n=10/63). There were 20 boys and the median age was 10 years. Patients with neurological symptoms due to other causes were excluded. Acute neurological symptoms developed following induction chemotherapy in 7 patients, or after a more intensive course of chemotherapy containing high-dose methotrexate (n=14). Nine patients required their chemotherapy to be altered because of the acute neurotoxicity. One patient died of cerebral haemorrhage but none of the remaining six deaths was attributed to acute neurotoxicity. We conclude that acute neurotoxicity is common in children treated with the 9002/9003 protocols and tends to be transient. Intrathecal and systemic chemotherapy including high-dose methotrexate is probably the most common predisposing factor. Modification of subsequent chemotherapy is not invariably necessary.

Acute Disease↗

Microbiological water quality in a large in-building, water recycling facility.

The Thames Water recycling plant at the Millennium Dome, London, reclaimed three sources of water: greywater from the washbasins, rainwater from the Dome roof and groundwater from a borehole on site. These were pre-treated separately, and the mixed stream filtered using ultrafiltration and reverse osmosis membranes. Monitoring for indicator microorganisms was undertaken throughout the plant and in the reclaimed water distribution system, as well as ad-hoc monitoring for the presence of pathogens in the raw waters. Treatment to the level of ultrafiltration was more than adequate to produce a water quality meeting existing worldwide reclaimed water guidelines for toilet flushing. Owing to the excellent quality of the water leaving the plant, no significant microbiological growth was observed in the reclaimed water distribution system during the year. The raw greywater exhibited a higher faecal bacterial load than the rainwater and groundwater, as predicted from more human contact (i.e. hand washing). Environmental strains of Legionella were observed in the three raw greywater samples analysed for pathogens, as was Cryptosporidium, Giardia and faecal enterococci. The rainwater had relatively high levels of faecal bacteria, probably of avian origin. Giardia was detected in one rainwater sample confirming the potential for this water source to contain pathogens.

Conservation of Natural Resources↗

Temozolomide in malignant gliomas of childhood: a United Kingdom Children's Cancer Study Group and French Society for Pediatric Oncology Intergroup Study.

PURPOSE: To determine the response rate of the malignant gliomas of childhood to an oral, daily schedule of temozolomide. PATIENTS AND METHODS: A multicenter, phase II evaluation of an oral, daily schedule of temozolomide (200 mg/m(2) on 5 consecutive days) was undertaken in children with relapsed or progressive, biopsy-proven, high-grade glioma (arm A) and progressive, diffuse, intrinsic brainstem glioma (arm B). Evidence of activity was defined by radiologic evidence of a sustained reduction in tumor size on serial magnetic resonance imaging scans. RESULTS: Fifty-five patients were recruited (34 to arm A and 21 to arm B) and received 215 cycles of chemotherapy. Grade 3/4 thrombocytopenia was the most frequent toxic event (7% of cycles). Prolonged myelosuppression resulted in significant treatment delays and dose reductions (17% and 22% of cycles, respectively). Two toxic deaths were documented and were related to myelosuppression and sepsis in one patient and pneumonia in a second. The overall (best) response rate was 12% for arm A (95% confidence interval [CI], 3 to 28 in the study cohort, and 2 to 31 for eligible patients) and 5% and 6%, respectively, for arm B (95% CI, 0 to 26 in the study cohort, and 0 to 27 for eligible patients). Stabilization of disease was also documented and was most noteworthy for brainstem gliomas, where two patients achieved both radiologic static disease and discontinued steroid medication. CONCLUSION: Despite moderate toxicity, objective response rates to temozolomide have been low, indicating that temozolomide has minimal activity in the high-grade gliomas of childhood.

Adolescent↗

Immunodeficiency-related lymphoproliferative disorders: prospective data from the United Kingdom Children's Cancer Study Group Registry.

Clinical data and biological samples were prospectively collected in 42 children with lymphoproliferative disease (LPD) secondary to organ/bone marrow transplant-related immunosuppression (30: 11 liver, 10 heart/lung, 8 kidney and 1 bone marrow), other drug-induced immunosuppression (2), congenital immunodeficiency (8) or human immunodeficiency virus (HIV)-related immune dysfunction (2). Ages ranged from 10 months to 17 years and there were 15 girls. Pathology was centrally reviewed and showed polymorphic features in 5 cases, monomorphic in 23, mixed pattern in 5 patients and 9 other types. Using the Revised European-American Classification of Lymphoid Neoplasms, 5 were B lymphoblastoid, 24 were high-grade B and 14 were other subtypes. Using the Pittsburgh classification, 9 were lymphadenopathic, 10 were systemic, 25 were lymphomatous and, with the Murphy grouping for non-Hodgkin's lymphoma (NHL), 10 were localized and 32 non-localized. Twenty-four out of 38 evaluable cases were Epstein-Barr virus positive. Thirty-five patients were evaluable for clonality; 24 were monoclonal and 11 were polyclonal. Reduced immunosuppression in solid organ transplant patients resulted in resolution of disease in 14/24, which was sustained in 11. Nineteen patients received chemotherapy, 14/18 evaluable responded, which was sustained in 8 cases. Seven out of 29 solid organ transplant and 10/13 other immune-deficient patients died. In the largest group of patients, solid organ transplants, no significant clinical or biological characteristics that predicted outcome were identified. In the transplant group close monitoring of response during reduction in immunosuppression is essential and the early use of B NHL chemotherapy may be effective.

Adolescent↗

A phase I study of nolatrexed dihydrochloride in children with advanced cancer. A United Kingdom Children's Cancer Study Group Investigation.

A phase I study of nolatrexed, administered as a continuous 5 day intravenous infusion every 28 days, has been undertaken for children with advanced malignancy. 16 patients were treated at 3 dose levels; 420, 640 and 768 mg/m(2)24 h(-1). 8 patients were evaluable for toxicity. In the 6 patients treated at 768 mg/m(2)24 h(-1), dose-limiting oral mucositis and myelosuppression were observed. Plasma nolatrexed concentrations and systemic exposure, measured in 14 patients, were dose related, with mean AUC values of 36 mg(-1)ml(-1)min(-1), 50 mg ml(-1)min(-1)and 80 mg ml(-1)min(-1)at the 3 dose levels studied. Whereas no toxicity was encountered if the nolatrexed AUC was <45 mg ml(-1)min(-1), Grade 3 or 4 toxicity was observed with AUC values of >60 mg ml(-1)min(-1). Elevated plasma deoxyuridine levels, measured as a surrogate marker of thymidylate synthase inhibition, were seen at all of the dose levels studied. One patient with a spinal primitive neuroectodermal tumour had stable disease for 11 cycles of therapy, and in two patients with acute lymphoblastic leukaemia a short-lived 50% reduction in peripheral lymphoblast counts was observed. Nolatrexed can be safely administered to children with cancer, and there is evidence of therapeutic activity as well as antiproliferative toxicity. Phase II studies of nolatrexed in children at the maximum tolerated dose of 640 mg/m(2)24 h(-1)are warranted.

Acute Disease↗

Outcome of relapsed or refractory childhood B-cell acute lymphoblastic leukaemia and B-cell non-Hodgkin's lymphoma treated with the UKCCSG 9003/9002 protocols.

Twenty-six children with B-cell acute lymphoblastic leukaemia (B-ALL) or Murphy Stage III or IV B-cell non-Hodgkin's lymphoma (B-NHL) progressed or relapsed after first-line therapy with a short, intensive multiagent chemotherapy regimen [United Kingdom Childhood Cancer Study Group (UKCCSG) 9003] (n = 62) or a slightly less intensive regimen (UKCCSG 9002) (n = 112). Eight patients (4.6%) never achieved complete remission (CR) and 18 (10.3%) relapsed. Second-line therapy resulted in remission for eight patients (30%). All patients initially treated with the 9003 protocol died. Three patients (11.5%) in the 9002 group, including one who never achieved CR in the primary site, are alive after second-line therapy. This study confirms that the prognosis of relapsed or refractory B-ALL/B-NHL is poor and exceptionally so if relapse occurred less than 6 months from diagnosis. High-dose therapy with stem cell rescue was used in only seven patients; its role needs to be studied further.

Antineoplastic Combined Chemotherapy Protocols↗

Variations in acid-etch patterns with different acids and etch times.

Research has shown that mandibular premolars have the highest rate of orthodontic bracket bond failure. Bond strength is thought to depend on the quality and quantity of enamel etch produced by the acid. Phosphoric acid is the most commonly used acid for etching before bonding. Nitric acid is also commercially available for etching enamel; however, it has not been studied specifically for etching in orthodontic bonding. This ex vivo study compared the enamel etch patterns achieved on the orthodontic bonding area of extracted mandibular premolars treated with 37% wt/wt phosphoric acid and 2.5% wt/wt nitric acid applied for 15, 30, or 60 seconds. The etch patterns were viewed with a scanning electron microscope and assessed with a 5-point etch scale. Statistical analysis showed that increasing the duration of acid application (irrespective of acid type) significantly increased the amount of better quality etch. Phosphoric acid at 37% concentration was more effective at producing a good-quality etch than was nitric acid at 2.5% for all 3 application times. The quantity of good-quality etch produced by phosphoric acid at 37% was time specific, with 15 seconds being significantly less effective than 30 or 60 seconds. However, 60 seconds was not significantly better than 30. Comparing the upper half of the orthodontic bonding area with the lower half showed no statistically significant differences for either acid type or length of application (P >.005). These findings support the use of 37% wt/wt phosphoric acid and indicate an optimum application time of 30 seconds.

Acid Etching, Dental↗

Prospective validation of renal function-based carboplatin dosing in children with cancer: A United Kingdom Children's Cancer Study Group Trial.

PURPOSE: Carboplatin dosing in adults with cancer is based on renal function. The purpose of the current study was to validate a previously developed pediatric carboplatin-dosing formula. PATIENTS AND METHODS: Thirty-eight pediatric patients were randomized to receive a carboplatin dose calculated according to surface area or a renal function-based dosing formula. On the next course of therapy, the alternative dosing method was used for each patient. Carboplatin pharmacokinetics (based on free plasma platinum concentrations) were measured after both courses. RESULTS: The mean observed areas under the carboplatin concentration-versus-time curve (AUCs) after renal function- and surface area-based dosing were 98% and 95% of the target AUCs, respectively. The variation in the observed AUC was significantly less after renal function-based dosing (F test, P =.02), such that 74% of courses had an observed AUC within +/- 20% of the target value, versus 49% for courses after dosing according to surface area. Only one of 22 courses at the center with the most experience with renal function-based dosing was associated with an AUC outside +/- 20% of the target value, versus nine of 22 courses after surface area-based dosing in the same center. There was a relationship (r(2) =.71) between carboplatin AUC and thrombocytopenia in 10 neuroblastoma patients treated with a combination of carboplatin, vincristine, etoposide, and cyclophosphamide. CONCLUSION: Renal function-based carboplatin dosing in children results in more consistent drug exposure than surface area-based drug administration.

Adolescent↗

Improved outcome in children with advanced stage B-cell non-Hodgkin's lymphoma (B-NHL): results of the United Kingdom Children Cancer Study Group (UKCCSG) 9002 protocol.

From July 1990 to March 1996, 112 children with stage III or IV B-cell non-Hodgkin's lymphoma (B-NHL) with up to 70% FAB L3-type blasts (n = 42) in the bone marrow without central nervous system (CNS) disease were treated on the United Kingdom Children Cancer Study Group (UKCCSG) 9002 protocol (identical to the French LMB 84). The median age was 8.3 years. There were 81 boys and 31 girls. According to the extent of the primary disease, patients were sub-staged into three groups: IIIA with unresectable abdominal tumour (n = 39); IIIB with abdominal multiorgan involvement (n = 57) and IIIX with extra-abdominal primary lymphoma often presenting as pleural effusion (n = 16). Univariate and multivariate analyses were carried out to evaluate the prognostic significance of lactate dehydrogenase (LDH) level at diagnosis, the sub-stage and the time to achieve complete remission (CR). With a median follow up of 48 months (range 12-92), the overall and event free survival (EFS) is 87% (95% confidence interval (CI) 79.2-92.1 %) and 83.7% (95% CI 76.3-89.2%) respectively. Six patients (5.4%) never achieved CR, of whom one is alive following high-dose therapy. Eight patients (7.1%) relapsed after achieving CR, three are alive after second-line therapy. There were three early toxic deaths (2.7%), mainly from infection, and one late death from a second cancer. There was no significant difference in EFS according to LDH level at diagnosis, the sub-stage or the time to CR. This study confirms the overall good prognosis and low rate of toxic deaths in patients with advanced B-NHL treated with this intensive regimen. No significant difference in EFS according to the sub-stage, the time to achieve CR or LDH level at diagnosis making it difficult to identify a group that should not receive intensive therapy.

Adolescent↗

Improved cure rate in children with B-cell acute lymphoblastic leukaemia (B-ALL) and stage IV B-cell non-Hodgkin's lymphoma (B-NHL)--results of the UKCCSG 9003 protocol.

From June 1990 to February 1996, 35 patients with B-cell acute lymphoblastic leukaemia (B-ALL) 13 of whom had CNS disease and 28 patients with stage IV B-cell non-Hodgkin's lymphoma (B-NHL) 22 of whom had CNS involvement were treated with a short, intensive multiagent chemotherapy regimen (UKCCSG 9003 protocol) based on the French LMB 86 regimen. Fifty-five were boys. The age range was 11 months to 16.5 years (median 8.4 years). Chemotherapy included cyclophosphamide, vincristine, daunorubicin, high-dose methotrexate (COPADM) and etoposide/high-dose cytarabine (CYVE) with frequent intrathecal (i.t.) triple therapy (methotrexate, cytarabine and hydrocortisone). Cranial irradiation (24 Gy in 15 fractions) was recommended in patients with overt CNS disease. One patient with Wiskott-Aldrich syndrome was withdrawn after entry and has been excluded from the analysis. Ten patients (16%) have relapsed (CNS, four; BM, two; combined CNS and BM, three; and jaw, one) 4-11 months after diagnosis and two patients never achieved complete remission (CR). All have died. In seven of the patients who relapsed, treatment had been modified or delayed because of poor clinical condition. Seven patients (11%) died of toxicity 11 days to 4 months after diagnosis. The cause of death was sepsis (n = 5) or sepsis with renal failure (n = 2). With a median follow-up of 3.1 years from diagnosis (range 9 months to 6.3 years), 43 patients (69%) survive in CR. This study confirms the effectiveness of this regimen with regard to the relapse rate (16%), although the rate of toxic death is of concern.

Adolescent↗

Conservative management of follicular non-Hodgkin's lymphoma in childhood.

Among 447 children with non-Hodgkin's lymphoma (NHL) on the childhood U.K. registry, seven children with follicular (NHL) were identified. Four were male and their age ranged from 4.25 to 13.5 years (median 7.5); all had localized disease, Murphy's stage I (n = 4) and II (n = 3). Sites involved at presentation were cervical lymph nodes and tonsils (n = 5), ileum (n = 1) and parotid gland (n = 1). Three had complete surgical excision only and four had complete (n = 1) or incomplete excision (n= 3) followed by a short multi-agent chemotherapy regimen (UKCCSG 9001 protocol). With a median follow-up of 1.5 years (range 0.25-5 years) from diagnosis, six are alive in complete remission (CR) including three who had no chemotherapy. These results confirm previous reports that follicular lymphomas in children are rare (1.5%) and tend to be localized at presentation. Their rarity makes it difficult to produce guidelines about treatment, but in localized cases a period of non-intervention may be justified.

Antineoplastic Agents↗

Burkholderia (Pseudomonas) cepacia as a cause of brain abscesses secondary to chronic suppurative otitis media.

A patient with a cholesteatoma secondary to chronic suppurative otitis media developed infective complications including cerebellar and cerebello-pontine abscesses. Burkholderia cepacia was isolated from ear swabs, infected tissue and surgical pus on five occasions over a six-month period. Despite exhibiting three different antibiotic susceptibility profiles, all five isolates were confirmed as clonally indistinguishable by pulsed-field gel electrophoresis. To the best of the authors' knowledge there are no previous reports of Burkholderia cepacia causing infection of the adult central nervous system.

Adult↗