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Biomedical subjects

D A Walker

Publications and source records attributed to D A Walker.

At least 37 records · Page 2Linked to original sources

Wilms' tumor: a 25-year review of the role of preoperative chemotherapy.

PURPOSE: This 25-year population based, single institution review was conducted to investigate the impact of preoperative chemotherapy on surgical and histological staging in patients with Wilms' tumors. RESULTS: Forty-nine patients under the age of 15 years were identified from case notes to have had histologically verified Wilms' tumors over the 25-year period from January 1972 to December 1996. Twenty-six patients were treated initially with preoperative chemotherapy, 23 with immediate surgery. Eleven had treatment randomized within the UKCCSG WT9101 trial (UKWT3), and the remainder received initial treatment according to unit policy. Surgical stages in the two groups (preoperative chemotherapy and immediate surgery) were respectively, stage 1:14(28.5%) and 11 (22.5%), stage II: one (2%) and eight (16.3%), stage III: 11 (22.5%) and four (8.2%). Seven patients had clinical stage IV disease at presentation. Histology results were favorable in 45 patients and unfavorable in four. All patients received chemotherapy during treatment, whereas 25 (51%) also received radiotherapy. No significant difference was evident in the two groups with respect to treatment-related morbidity. Five patients relapsed, three of whom died within the period of review, but a fourth has since died. CONCLUSIONS: This study suggests that the use of preoperative chemotherapy does not put the patient at increased risk of postoperative morbidity or reduced survival. The distribution of surgical stages suggests that limited tumor downstaging may have occurred as a result of preoperative chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Applicability of the Health Utilities Index to a population of childhood survivors of central nervous system tumours in the U.K.

This paper describes the application of a multi-attribute, preference-linked health status and health-related quality of life measurement system--the Health Utilities Index (developed in Canada)--to a group of subjects in the U.K. Children who had survived tumours of the central nervous system (n = 30, age 6-16 years) formed the study group. Respondents (children, parents, physicians and physiotherapists) found the activity (completion of a 15-item questionnaire) to be acceptable and not burdensome (it was accomplished easily by all children > or = 10 years of age). Instrumental reliability was established by acceptable intra- and interobserver agreement and construct validity was supported by strong similarities between the results obtained in this study and those reported from a similar group of children in Canada. The greatest burden of morbidity was reported for the attributes of emotion and cognition (each affected in > 50% of the children). Pain was surprisingly prevalent (affected in approximately one-third of children). The finding of a large number of unique health states emphasises the complex morbidity burden experienced by these children who self-reported poorer overall health (as reflected in utility scores) than did the proxy respondents. The information obtained from this study is readily interpretable and clinically useful. The results of this study also illustrate that extreme caution must be exercised in undertaking linguistic modifications to established instruments for, in this instance, these resulted in a loss of the ability to detect the most severe emotional morbidity and reduced the comparability of results between studies. With this provision, the Health Utilities Index is evidently applicable in the U.K. and the original version has been recommended for use in brain tumour studies by the U.K. CCSG (the U.K. Children's Cancer Study Group).

Adolescent↗

Modified antisense oligonucleotides directed against tumor necrosis factor receptor type I inhibit tumor necrosis factor alpha-mediated functions.

Tumor necrosis factor alpha (TNF alpha), a polypeptide produced by activated macrophages, is a highly pleiotropic cytokine which elicits inflammatory and immunological reactions. The binding of TNF alpha to tumor necrosis factor receptor type I (TNFRI) is considered the initial step responsible for some of the multiple biological functions mediated by TNF alpha. The role of TNF alpha as an inflammatory mediator through human TNFRI makes TNFRI an attractive target for intervention in both acute and chronic inflammatory diseases. In this study, we have identified partial phosphorothioate oligodeoxyribonucleotides (ODNs) containing C-5 propynyl or hexynyl derivatives of 2'-deoxyuridine which specifically inhibited TNFRI and subsequently inhibited the functions of TNF alpha mediated through TNFRI. The most active ODNs were directed against the 3'-poly adenylation signal site on the TNFRI mRNA, and in a cellular assay, gene-specific antisense inhibition occurred in a dose-dependent fashion at submicromolar concentrations, in the presence of Cellfectin. The inhibition of gene expression correlated with the binding affinity of the ODN for the target mRNA. The ODNs lowered TNFRI protein levels and TNF alpha-mediated functions by specifically reducing levels of TNFRI mRNA. These anti-TNFRI ODNs offer a novel approach for controlling biological functions of TNF alpha and may be useful as human therapeutic agents for treating diseases in which TNF alpha has been implicated.

Antigens, CD↗

School behaviour and health status after central nervous system tumours in childhood.

This study was designed to assess the overall morbidity burden of survival from central nervous system (CNS) tumours and its impact on return to a normal lifestyle. School behaviour and health status of 27 children after treatment for CNS tumours, of 25 of their school-aged siblings, plus age- and sex-matched controls is reported. Spinetta school behaviour, Lansky play-performance and Health Utilities Index (mark II and III) assessments have been made. Patients had reduced mobility and increased pain levels. They demonstrated a reluctance to participate in organized physical activities. Impaired cognition, emotion and self-esteem were reported. They worried more than controls but attended school willingly, interacted normally with their peers and viewed the future confidently. Their siblings were reluctant to express openly concern for others or feelings of joy. Teachers were reliable proxies for most attributes, notable exceptions being speech and emotion. This is the first study to have assessed the school behaviour of a cohort solely composed of survivors of childhood CNS tumours. The good social reintegration is reassuring and likely to reflect a high level of psychosocial support. However, the results presented identify these young people as a 'special educational needs' group as defined by the 1981 and 1993 Education Acts.

Adolescent↗

Surgically assisted rapid orthodontic lengthening of the maxilla in primates--a pilot study.

Orthodontic and surgical treatment of patients with maxillary retrusion and/or midface hypoplasia is challenging. This study was designed to show that the maxilla can be successfully lengthened by surgical assisted rapid orthopedic movement, using the principles of distraction osteogenesis. Three experimental and three control adolescent cynomolgus primates were used in this study. Metallic markers were placed in the cranial base and the maxilla and cephalometric x-ray films were taken. An orthodontic appliance was constructed with a Glen-Ross screw (Dentaurum, Newtown, Pa.) oriented anteroposteriorly. Anterior supraapical osteotomies of the maxilla were carried out. Bilateral horizontal and interdental osteotomies were created between the first premolars and the canine; the anterior six tooth dental-osseo segment was completely mobilized in all animals. Beginning 1 week after surgery, the orthodontic appliance was opened a quarter turn every 2 days until the anterior segment was advanced by 4 mm in two animals and 6 mm in one animal. Animals were killed at 6, 8, and 12 weeks after completion of the maxillary orthopedic advancement. Computerized tomographic scans of the maxillae were completed, and the specimens were then prepared by routine histologic methods for examination by light microscopy. The computerized tomographic scans showed bone deposition in the osteotomy sites, which was confirmed by histologic observations. Since this technique demonstrated repair by bone rather than soft connective tissue in the osteotomy sites, this procedure could be a useful method of treating midface retrusion.

Animals↗

Tori mandibularis: a case report and review of the literature.

Many dentists have patients in their practice with mandibular exostoses, termed torus mandibularis. The majority of these asymptomatic, benign bony outgrowths remain undisturbed over the patient's lifetime. However, the tori occasionally need to be removed. The differential diagnosis for the tori are discussed as well as the indications and techniques for their removal. Various hypotheses concerning the etiology and epidemiology of torus mandibularis are also reviewed.

Adult↗

Rapid orthopedic lengthening of the mandible in primates by sagittal split osteotomy and distraction osteogenesis: a pilot study.

This study proposes the development of an intraoral surgical approach to distraction osteogenesis to treat maxillofacial defects. Bilateral sagittal split osteotomies were made in the ascending ramus and body of the mandible of two adult cynomologus primates, and the dento-osseous segment was completely mobilized. A distraction device was fabricated from a Glen-Ross screw soldered between two mini bone plates. The bone plates were fixed by self-tapping screws to both right and left proximal and distal mandibular segments. Beginning 1 week postoperatively, both distraction plates were opened 1 mm every day until the mandible was advanced a total of 10 mm. Comparison of cephalometric radiographs and study casts prepared preoperatively, at the completion of the mandibular orthopedic advancement, and up to 12 weeks postdistraction, showed that mandibular advancement was successful and stable. There was radiographic evidence of bone filling the osteotomy sites, and there was no scar tissue formation or evidence of relapse.

Animals↗

Surgically assisted-rapid orthopedic lengthening of the maxilla in primates--relapse following distraction osteogenesis.

A recent study has shown that the maxilla in primates can be successfully lengthened (0.5 mm every other day up to 6.0 mm) by means of surgically assisted-rapid orthopedic movement, using the principles of distraction osteogenesis. The present study was designed to determine if the maxilla can be advanced at a faster rate and if relapse would occur after removal of the orthodontic appliance. Metallic markers were placed in the cranial base and maxilla of two Cynomolgus primates, and cephalometric radiographs were taken. Bilateral horizontal and interdental osteotomies were created between in the first premolars and the canines, and the anterior segment was completely mobilized. An orthodontic appliance was bonded to the teeth and the screw was closed, compressing the osteotomy site. One week postoperatively the appliance was opened four quarter turns every day until the anterior segment was advanced by 10 mm. Cephalometric radiographs were taken at 6, 8, and 12 weeks postadvancement. At 12 weeks, the orthodontic appliance was removed, and at that time and 2, 4, and 6 weeks later, cephalometric radiographs were taken and study models fabricated. At the end of the postretention period, the animals were sacrificed, and the maxillae were evaluated by light microscopy. Results showed that the maxilla can be successfully advanced at a faster rate and for longer distances, and that the advanced maxilla does not relapse during the 6-week postretention period.

Animals↗

Assessment of health status in survivors of cancer.

The health status of 48 survivors of cancer was assessed using a rating system for six attributes: senses, mobility, emotion, cognition, self care, and pain. Paired assessments were made by doctors and patients (or their parents, or both) at routine clinic attendances. Sixteen (33%) assessments by the patient/parent and 19 (40%) assessments by the doctor identified no deficits in health status. The doctors identified fewer deficits in all attributes than the patients/parents, the differences being most marked for subjective attributes. Health status index scores on a scale of 0 (worst health state) to 1 (perfect health) were derived from the rating system and showed good overall agreement between the doctors and the patients/parents. Survivors of neuroaxial tumours tended to have lower scores than other diagnostic groups. This simple, compact system could be used in clinical trials to compare treatment strategies in terms of the health status of survivors. It could also be a valuable tool in the assessment of health status in other areas of paediatrics.

Activities of Daily Living↗