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Biomedical subjects

C Brock

Publications and source records attributed to C Brock.

At least 19 recordsLinked to original sources
PubMed2000

NCCN Practice Guidelines for Cancer Pain.

The overall approach to pain management encompassed in these guidelines is comprehensive. It is based on objective pain assessments, utilizes both pharmacologic and nonpharmacologic interventions, and requires continual reevaluation of the patient. The NCCN Cancer Pain Practice Guidelines Panel believes that cancer pain can be well controlled in the vast majority of patients if the algorithms presented are systematically applied, carefully monitored, and tailored to the needs of the individual patient.

Acetaminophen↗
PubMed1999

Loss of chromosome 10 is an independent prognostic factor in high-grade gliomas.

Loss of heterozygosity (LOH) for chromosome 10 is the most frequent genetic abnormality observed in high-grade gliomas. We have used fluorescent microsatellite markers to examine a series of 83 patients, 34 with anaplastic astrocytoma (grade 3) and 49 with glioblastoma multiforme (grade 4), for LOH of chromosome 10. Genotype analysis revealed LOH for all informative chromosome 10 markers in 12 (35%) of patients with grade 3 and 29 (59%) grade 4 tumours respectively, while partial LOH was found in a further eight (24%) grade 3 and ten (20%) grade 4 tumours. Partial LOH, was confined to the long arm (10q) in six and the short arm (10p) in three cases, while alleles from both arms were lost in four cases. Five tumours (one grade 3 and four grade 4) showed heterogeneity with respect to loss at different loci. There was a correlation between any chromosome 10 loss and poorer performance status at presentation (chi2 P = 0.005) and with increasing age at diagnosis (Mann-Whitney U-test P = 0.034) but not with tumour grade (chi2 p= 0.051). A Cox multivariate model for survival duration identified age (proportional hazards (PH), P= 0.004), grade (PH, P= 0.012) and any loss of chromosome 10 (PH, P= 0.009) as the only independent prognostic variables. Specifically, LOH for chromosome 10 was able to identify a subgroup of patients with grade 3 tumours who had a significantly shorter survival time. We conclude that LOH for chromosome 10 is an independent, adverse prognostic variable in high-grade glioma.

Brain Neoplasms↗
PubMed1998

New synthetic non-peptide ligands for classical major histocompatibility complex class I molecules.

Poly-N-acylated amines, as a new class of synthetic non-peptide ligands for the murine major histocompatibility complex (MHC) class I molecule H-2Kb, were developed on the basis of the ovalbumin-derived peptide epitope SIINFEKL. Non-peptidic structural elements were introduced at the C-terminal part of the ligand and include the two dominant anchors at positions 5 and 8. Several oligomers and five different combinatorial libraries were synthesized and tested for their H-2Kb-binding capacities in an MHC stabilization assay. First, the optimal spacing and geometry of the side chains were determined using a series of oligomers with different main chain modifications. Then, based on the structure with the highest binding efficiency, randomized libraries were designed that contain 26 different aromatic, heteroaromatic, or pseudoaromatic side chains for the dominant anchor at position 5, which is deeply buried inside the MHC peptide-binding groove and is crucial for the conformational stability of the entire peptide-MHC complex. Similarly, a series of aliphatic side chains were tested for the second dominant anchor at position 8. MHC-binding and MHC-stabilizing oligomers with defined structures were derived from these libraries by deconvolution.

Amines↗
PubMed1998

The management of high-risk gestational trophoblastic tumours (GTT).

Between 1979 and 1995 we have treated 272 consecutive women with high-risk (GTT including 121 previously treated patients who were treated with the weekly EMA/CO (etoposide, methotrexate, actinomycin D alternating with cyclophosphamide and vincristine). The median follow-up is 4.5 years (range 1-16 years). The cumulative 5 year survival is 86.2% (95% confidence interval 81.9-90.5%). No deaths from GTT occurred later than 2 years after starting EMA/CO. In a multivariate analysis, adverse prognostic factors were the presence of liver metastases (p < 0.0001), interval from antecedent pregnancy > 24 months (p < 0.0001), brain metastases (p=0.0008) and term delivery of antecedent pregnancy (p=0.045). There were 11 (4%) early deaths while 213 (78%) achieved complete remission. 47 (17%) developed drug resistance to EMA/CO of whom 33 (70%) were salvaged by further cisplatinum based chemotherapy and surgery. 2 women developed acute myeloid leukaemia after treatment with EMA/CO. 56% of women who have been in remission for at least 2 years and had fertility conserving surgery have achieved pregnancy since completing EMA/CO and there have been 112 live births including 3 babies with congenital abnormalities. EMA/CO is an effective, easy to administer and well tolerated regimen for treating patient with high-risk GTT. More than half of these women will retain their fertility. However, there is a small but significant increase in second malignancies.

Adolescent↗
PubMed1997

POMB/ACE chemotherapy for mediastinal germ cell tumours.

Mediastinal germ cell tumours (MGCT) are rare and most published series reflect the experiences of individual institutions over many years. Since 1979, we have treated 16 men (12 non-seminomatous germ cell tumours and 4 seminomas) with newly diagnosed primary MGCT with POMB/ACE chemotherapy and elective surgical resection of residual masses. This approach yielded complete remissions in 15/16 (94%) patients. The median follow-up was 6.0 years and no relapses occurred more than 2 years after treatment. The 5 year overall survival in the non-seminomatous germ cell tumours (NSGCT) is 73% (95% confidence interval 43-90%). One patient with NSGCT developed drug-resistant disease and died without achieving remission and 2 patients died of relapsed disease. In addition, 4 patients with bulky and/or metastatic seminoma were treated with POMB/ACE. One died of treatment-related neutropenic sepsis in complete remission and one died of relapsed disease. Finally, 4 patients (2 NSGCT and 2 seminomas) referred at relapse were treated with POMB/ACE and one was successfully salvaged. The combination of POMB/ACE chemotherapy and surgery is effective management for MGCT producing high long-term survival rates.

Adolescent↗
PubMed1997

EMA/CO for high-risk gestational trophoblastic tumors: results from a cohort of 272 patients.

PURPOSE: To evaluate the results of etoposide, methotrexate, and dactinomycin alternating with cyclophosphamide and vincristine (EMA/CO) chemotherapy in women with high-risk gestational trophoblastic tumors (GTT) and to document the middle- and long-term toxicity of the regimen. PATIENTS AND METHODS: A total of 272 consecutive women with high-risk GTT, including 121 previously treated patients, were treated with weekly EMA/CO. The median follow-up duration is 4.5 years (range, 1 to 16). RESULTS: The cumulative 5-year survival rate is 86.2% (95% confidence interval, 81.9% to 90.5%). No deaths from GTT have occurred later than 2 years after the end [corrected] of EMA/CO. In a multivariate model, adverse prognostic factors were the presence of liver metastases (P < .0001), interval from antecedent pregnancy (P < .0001), brain metastases (P = .0008), and term delivery of antecedent pregnancy (P = .045). There were 11 (4%) early deaths, while 213 patients (78%) achieved a complete remission. Forty-seven (17%) developed drug resistance to EMA/CO, of whom 33 (70%) were salvaged by further cisplatin-based chemotherapy and surgery. Two women developed acute myeloid leukemia, two cervical malignancy, and one gastric adenocarcinoma after EMA/CO. More than half (56%) of the women who had fertility-conserving surgery and who have been in remission at least 2 years have become pregnant since the completion of EMA/CO, with 112 live births, including three infants with congenital abnormalities. CONCLUSION: EMA/CO is an effective and well-tolerated regimen for high-risk GTT. More than half of the women will retain their fertility; however, there is a small but significant risk of second malignancy.

Adolescent↗
PubMed1996

A weekly alternating chemotherapy regimen with low toxicity for the treatment of aggressive lymphoma.

A total of 50 consecutive adult patients with newly diagnosed aggressive non-Hodgkin's lymphoma were treated with a weekly alternating combination chemotherapy schedule, BEMOP/CA, including bleomycin, etoposide, methotrexate, vincristine, cyclophosphamide and Adriamycin. Two-thirds of the patients were over 60 years old or had stage 4 disease. Clinical remission was achieved in 56% of cases. The 3-year survival is 53% (95% confidence interval, 39-66%). The presence of B symptoms and a serum albumin value of <33 g/l at presentation were poor prognostic indicators for survival in a multivariate proportional-hazards model. Overall, the response rate and survival for this group of patients with intermediate- and high-grade lymphomas is similar to results previously reported. The BEMOP/CA treatment was brief (16 weeks) and associated with a low fatal toxicity (one early death and one late fatality from Pneumocystis pneumonia), and the drug costs are equivalent to those for eight cycles of CHOP.

Adolescent↗
PubMed1996

The Charing Cross Hospital experience with temozolomide in patients with gliomas.

Temozolomide, a new oral cytotoxic agent, was given to 75 patients with malignant gliomas. The schedule used was for the first course 150 mg/m2 per day for 5 days (i.e. total dose 750 mg/m2), escalating, if no significant myelosuppression was noted on day 22, to 200 mg/m2 per day for 5 days (i.e. total dose 1000 mg/m2) for subsequent courses at 4-week intervals. There were 27 patients with primary disease treated with two courses of temozolomide prior to their radiotherapy and 8 (30%) fulfilled the criteria for an objective response. There were 48 patients whose disease recurred after their initial surgery and radiotherapy and 12 (25%) fulfilled the criteria for an objective response. This gave an overall objective response rate of 20 (27%) out of 75 patients. Temozolomide was generally well tolerated, with little subjective toxicity and predictable myelosuppression. However, the responses induced with this schedule were of short duration and had relatively little impact on overall survival. In conclusion, temozolomide given in this schedule has activity against high grade glioma. However, studies evaluating chemotherapy in primary brain tumours should include a quality-of-life/performance status evaluation in addition to CT or MRI scanning assessment.

Adult↗
PubMed1996

Whole body protein metabolism in children with cancer.

Whole body protein synthesis and catabolism were measured using the [ring-2H5]phenylalanine and [1-13C]leucine primed constant infusion technique in 32 paediatric patients with cancer at different stages of treatment. Rates of synthesis (S) and catabolism (C) derived from the [ring-2H5]phenylalanine and [1-13C]leucine models were 4.7 (SD 1.3) (S) and 6.0 (1.5) (C) g/d/kg, and 5.5 (0.8) (S) and 6.8 (1.2) (C) g/d/kg, respectively. These results show that these two tracer techniques give similar results in this study population. Comparison of these values with results previously reported for groups of control children using the [ring-2H5]phenylalanine model (S = 3.69 and 3.93; C = 4.09 and 4.28 g/d/kg) and the [1-13C]leucine model (S = 4.32; C = 4.85 g/d/kg) show that rates of synthesis and catabolism were higher in cancer patients than in controls. Thus whole body protein turnover is increased in children under treatment for cancer. Other indices of metabolism such as plasma amino acids and intermediary metabolites were also measured and showed that, although subjects were in isotopic steady state, there were significant metabolic changes during the course of the primed constant infusions used to measure protein turnover.

Adolescent↗
PubMed1995

A school and community outbreak of influenza A.

In May 1995 a department of public health medicine was informed of an outbreak of respiratory and gastrointestinal illness in a local school. Eighty-three pupils and staff were affected out of a total of 247 people--an attack rate of 34%. The outbreak was investigated, control measures were instigated, and the outbreak subsided. Pupils and staff were surveyed and faecal specimens were collected. Blood specimens from a sample of pupils were examined serologically. No organisms were isolated from faecal specimens. Nine of the 18 blood specimens taken showed raised antibody titres against influenza A. This labour intensive investigation revealed a community outbreak of influenza A. Investigations in schools can be useful in community surveillance.

Antibodies, Viral↗
PubMed1994

Mechanical anastomosis of nerves: a histological and functional comparison to conventional suturing.

The use of a mechanical coupling device in microsurgery offers speed of application in addition to a secure vascular union. Despite its success in a vascular setting, mechanical coupling device nerve repair remains to be studied. Forty-five male rats were tested over 7- and 14-week study periods. One half of the animals underwent primary suture repairs for transected sciatic nerves, and the remainder of the animals had their nerves repaired using a mechanical coupling device. Postoperative analysis consisted of histological evaluation of pre- and postrepair site nerve morphology (axonal continuity and counts) as well as functional testing using walking track analysis. Mechanical coupling device coaptation of the nerves using the epineurium was done in approximately one half the time compared with conventional suturing. After both 7 and 14 weeks postoperatively, walking track analysis showed no difference in the amount of functional return between the two repair groups. No animal exhibited complete return of function. Axonal continuity occurred across both repairs without significant difference in their pre- and postrepair axonal counts. Although no clear advantage was seen in this study, the concept of mechanical nerve coupling merits further investigation based on its potential clinical utility.

Anastomosis, Surgical↗
PubMed1993

Does the rapid response to cisplatin-based chemotherapy justify its use as primary treatment for intracranial germ-cell tumours?

We reviewed presentation, diagnostic problems and outcome of eight cases of primary intracranial germ-cell tumour (4 germinoma, 4 teratoma) treated with Cisplatin-based chemotherapy at our centre over the last ten years. Three patients received primary chemotherapy with Cisplatin-based regimens followed by radiotherapy for subsequent relapse, two were treated with a combination of chemotherapy and external radiotherapy, and three received chemotherapy for relapse after radiotherapy. The response to Cisplatin-based chemotherapy was rapid, with some patents exhibiting symptomatic improvement within 24 h. Four patients achieved complete remission within 21 days, and three of these have remained progression-free. Four patients in total have survived for 32 to 128+ months. Six of seven patients tested pre-treatment had central diabetes insipidus and five had partial anterior pituitary failure. The endocrine deficit progressed in two, with no recovery in any patient. It is arguable that chemotherapy should be the primary therapy in all such cases diagnosed on the basis of tumour markers and imaging, with surgery and/or radiotherapy as later options. As these tumours are rare, such questions can only be answered by collaboration studies.

Adolescent↗