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Biomedical subjects

F Cameron

Publications and source records attributed to F Cameron.

At least 19 recordsLinked to original sources
PubMed2005

Importance of radiation time and dose factors on outcome for childhood medulloblastoma.

The purpose of this study was to investigate the relationship of posterior fossa radiation therapy duration (PFRTD) and relapse-free survival (RFS) following adjuvant craniospinal RT for childhood medulloblastoma. A retrospective audit was performed assessing all children aged <18 years managed with adjuvant craniospinal RT for medulloblastoma in Australia and New Zealand in 1980-1993. Children receiving prolonged (>180 days) pre-RT chemotherapy were excluded. Data were obtained for potential prognostic factors in domains of patient, tumour and treatment factors. Radiation therapy time factors assessed were PFRTD and time interval from surgery to commencement of RT (SRTD). The end-point assessed was RFS and analysis was performed using Cox regression and Kaplan-Meier survival. One hundred and eighty-nine children were identified from 10 oncology units, with data available from 182 children for analysis. Median follow up was 5.3 years. Seventy-three per cent of children presented with disease confined to the cerebellum; 13% had initial neuraxis disease. Macroscopic resection was described in 54%; 42% received adjuvant chemotherapy. Median RT dose and RT duration to PF was 55 Gy and 45 days, respectively. Seventy-eight relapses occurred with a 10-year actuarial RFS of 58.2% (standard error +/- 4%). On univariate analysis, increasing PF dose (P = 0.002), age >5 years (P = 0.006), and more thorough extent of surgical resection (P = 0.043) were associated with improved RFS; PFRTD (P = 0.20) and SRTD (P = 0.51) were not associated with RFS. On multivariate analysis, although both PF dose (P = 0.004) and extent of surgery (P = 0.045) remained strongly significant, RT duration was now associated with RFS (P = 0.049). Other factors assessed that did not reach significance were patient age, local tumour extent, presence of internal shunt and use of chemotherapy. The importance of local treatment factors was confirmed in this audit with established prognostic factors such as primary tumour macroscopic resection and adequate PF RT dose being associated with RFS. A treatment time effect is weakly suggested, although less significant than RT dose delivered.

Adolescent↗
PubMed2005

Cisplatin and gemcitabine induction chemotherapy followed by concurrent chemoradiotherapy or surgery for locally advanced non-small cell lung cancer.

BACKGROUND: We report a study of induction chemotherapy followed by concurrent chemoradiotherapy for stage IIIA/IIIB non-small cell lung cancer. METHODS: Patients received two cycles of induction chemotherapy with cisplatin 100 mg/m(2) on day 1 and gemcitabine 1000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. If the disease was resectable [corrected] surgery was followed with two further cycles. If unresectable, patients received cisplatin 100 mg/m(2) day 1, 29 with 5-fluorouracil 1000 mg/m(2) per 24 h continuous infusion for 96 h on days 2-5 and days 30-33 of the radiotherapy administration. Radiation therapy consisted of 63 Gy, 35 fractions, 7 weeks. RESULTS: Of 48 patients, 40% had a partial response to induction chemotherapy. Four of eleven patients with stage IIIA tumours had resectable disease. The remaining seven patients plus 37 with stage IIIB disease had chemoradiotherapy. Response at the completion of all therapy was 62% (IIIA 73%, IIIB 59%). For all patients the median survival was 15.3 months: 1 year and 3 years, 58% and 25%, respectively. Those with IIIB disease responding to induction chemotherapy had significantly superior survival to those that did not respond (37 months vs 11 months; P = 0.005). This remained significant from a landmark at 8 weeks after the start of treatment (P = 0.01). CONCLUSION: These results are equivalent to other studies using induction chemotherapy prior to concurrent chemoradiotherapy. Response to induction chemotherapy may have major prognostic significance.

Adult↗
PubMed2004

Preclinical evaluation of a prostate-targeted gene-directed enzyme prodrug therapy delivered by ovine atadenovirus.

Gene-directed enzyme prodrug therapy (GDEPT) based on the Escherichia coli enzyme, purine nucleoside phosphorylase (PNP), provides a novel strategy for treating slowly growing tumors like prostate cancer (CaP). PNP converts systemically administered prodrug, fludarabine phosphate, to a toxic metabolite, 2-fluoroadenine, that kills PNP-expressing and nearby cells by inhibiting DNA, RNA and protein synthesis. Reporter gene expression directed by a hybrid prostate-directed promoter and enhancer, PSMEPb, was assayed after plasmid transfection or viral transduction of prostate and non-CaP cell lines. Androgen-sensitive (AS) LNCaP-LN3 and androgen-independent (AI) PC3 human CaP xenografts in nude mice were injected intratumorally with an ovine atadenovirus vector, OAdV623, that carries the PNP gene under PSMEPb, formulated with cationic lipid for enhanced infectivity. Fludarabine phosphate was then given intraperitoneally for 5 days at 75 mg/m2/day. PNP expression was evaluated by enzymic conversion of its substrate using reverse phase HPLC. OAdV623 showed excellent in vitro transcriptional specificity for CaP cells. In vivo, expression of PNP persisted for > 6 days after OAdV623 injection and a single treatment provided 100% increase in tumor doubling time and > 50% inhibition of tumor growth for both LNCaP-LN3 and PC3 lines, with increased tumor necrosis and apoptosis and decreased tumor cell proliferation. OAdV623 significantly suppressed the growth of AS and AI human CaP xenografts in mice.

Adenine↗
PubMed2001

Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia.

We have previously shown that familial septo-optic dysplasia (SOD), a syndromic form of congenital hypopituitarism involving optic nerve hypoplasia and agenesis of midline brain structures, is associated with homozygosity for an inactivating mutation in the homeobox gene HESX1/Hesx1 in man and mouse. However, as most SOD/congenital hypopituitarism occurs sporadically, the possible contribution of HESX1 mutations to the aetiology of these cases is presently unclear. Interestingly, a small proportion of mice heterozygous for the Hesx1 null allele show a milder SOD phenocopy, implying that heterozygous mutations in human HESX1 could underlie some cases of congenital pituitary hypoplasia with or without midline defects. Accordingly, we have now scanned for HESX1 mutations in 228 patients with a broad spectrum of congenital pituitary defects, ranging in severity from isolated growth hormone deficiency to SOD with panhypopituitarism. Three different heterozygous missense mutations were detected in individuals with relatively mild pituitary hypoplasia or SOD, which display incomplete penetrance and variable phenotype amongst heterozygous family members. Gel shift analysis of the HESX1-S170L mutant protein, which is encoded by the C509T mutated allele, indicated that a significant reduction in relative DNA binding activity results from this mutation. Segregation analysis of a haplotype spanning 6.1 cM, which contains the HESX1 locus, indicated that only one HESX1 mutation was present in the families containing the C509T and A541G mutations. These results demonstrate that some sporadic cases of the more common mild forms of pituitary hypoplasia have a genetic basis, resulting from heterozygous mutation of the HESX1 gene.

Alleles↗
PubMed2001

Stimulation of appetite by alcohol.

To investigate the effects of alcohol on appetite and food intake, 26 males attended the laboratory on three occasions. On each occasion, they were given a standard breakfast. Visual analog scale ratings of hunger, desire to eat and fullness (appetite ratings) were recorded from before breakfast until their return to the laboratory for lunch. Thirty minutes before lunch, subjects either rested (baseline), were given 330 ml of a no-alcohol lager (264 kJ: no-alcohol condition) or 330 ml of the same lager spiked with 3 units of alcohol (24 g ethyl alcohol; total energy=969 kJ: alcohol condition). Ratings of appetite were taken before and after the preload or baseline rest period and again before and hourly after lunch. The test meal at lunch consisted of a buffet-style array of foods and chilled water. Ad libitum intake at lunch (excluding energy from alcohol) was significantly higher following alcohol (7301+/-442 kJ) compared to both baseline (6365+/-334 kJ) and the no-alcohol conditions (6479+/-289 kJ). Appetite ratings failed to demonstrate any differences between alcohol and the no-alcohol condition. Total energy intake (including energy from alcohol) was enhanced in the alcohol condition by 30%, suggesting that energy from alcohol is not compensated in the short-term and may even have a stimulatory effect on food intake.

Adult↗
PubMed2001

Review of the outcome of management of Graves' disease in children and adolescents.

OBJECTIVE: To review our recent experience in the management of paediatric Graves' disease, the leading cause of hyperthyroidism in childhood, in view of ongoing international debate regarding therapy. METHODOLOGY: Retrospective medical record review of patients with Graves' disease, treated between 1985 and 1999, at the Royal Children's Hospital, Melbourne. RESULTS: Forty patients, aged at diagnosis between 2.9 and 17.6 years (median age 11 years; 31 females), were treated. Thirty-three patients received either definitive therapy or at least 24 months medical therapy and follow up at the time of the study. Six patients experienced successful remission upon withdrawal of medication (median medication duration 3.2 years; four females; median follow up 4.1 years). Children successfully achieving remission were younger at presentation than those requiring surgery (9.5 vs 12.9 years, respectively; P = 0.01). Ten patients were treated surgically, leaving 4-6 g residual thyroid tissue. Surgical indications included failed initial medical therapy, relapse after medication cessation, non-compliance and significant medication side effects. During a median follow up of 1.7 years (range 0.2-5 years), three of 10 patients have subsequently relapsed and four of 10 patients are receiving postoperative thyroxine replacement. Transient hypocalcaemia occurred in five patients and temporary recurrent laryngeal nerve palsy occurred in two patients. CONCLUSIONS: Fewer than 20% of children experienced successful sustained remission at median follow up of 3.2 years. Medication remains a well-tolerated therapeutic option. Surgery is a reasonable alternative when there are specific indications. In order to decrease the likelihood of surgical relapse, less than 4 g thyroid tissue should be left postoperatively.

Adolescent↗
PubMed2000

Tris lipidation: a chemically flexible technology for modifying the delivery of drugs and genes.

1. One of the major challenges in the development of pharmaceuticals is their formulation with other materials to give them the desired bioavailability profile when administered into the body. 2. We have developed a flexible platform technology (Tris lipidation) to simply and effectively alter the lipophilicity of drugs. As implied by the name, the technology uses the common buffer Tris as a linker between the drugs of interest and a domain of variable hydrophobicity. 3. We demonstrate, using a mouse melanoma model, that Tris-lipidated conjugates of the widely used cytotoxic and anti-inflammatory drug methotrexate (MTX) display enhanced potency in the local treatment of tumours and reduced systemic toxicity when compared with the unconjugated drug. 4. With genes now being predicted to be the pharmaceuticals of the future, we show that Tris-lipidated cationic peptides can efficiently deliver DNA into (transfect) cells in culture. Furthermore, by comparing the abilities of variants of these Tris-based cationic lipids to transfect cultured cells, we demonstrate that modifications made to variable regions of Tris-lipidated compounds can dramatically alter their delivery profiles.

Animals↗
PubMed2000

The Child Health Questionnaire in children with diabetes: cross-sectional survey of parent and adolescent-reported functional health status.

AIMS: To study parent and adolescent-reported physical, psychosocial and family wellbeing in children aged 5-18 years with diabetes. METHODS SUBJECTS: 5-18-year-olds attending a diabetes clinic at a tertiary children's hospital. MEASURES: (1) Child Health Questionnaire (CHQ) PF-50, a functional heath status measure for children aged 5-18 years (parents); (2) CHQ CF-80, a similar self-report measure (adolescents aged 12-18 years); (3) 11 study-designed questions related to diabetes-specific concerns (parents); (4) global ratings of physical and psychosocial health (clinicians); (5) HbA1c level (all subjects). CHQ data were compared with Australian normative data collected six months earlier. RESULTS: Reports were obtained from 128 parents and 71 adolescents (90 and 92% response). The CHQ demonstrated good psychometric properties in this sample of children with diabetes. Parents reported children with diabetes to have generally poorer health than children in the normative sample, especially on psychosocial and parent/family scales. Psychosocial health was markedly lower in 5-11-year-olds with HbA1c > 8.8%, but not in 12-18-year-olds. Presence of diabetes-related symptoms and concerns correlated with lower physical and psychosocial functioning. Parents and clinicians concurred in their ratings of health for 12-18-year-olds but not 5-11-year-olds. Adolescents reported their own health similarly to adolescents in the normative sample. CONCLUSIONS: Parents report children aged 5-18 years with diabetes to have poorer health than children in the normative sample across all domains. Clinicians may underrate the impact of diabetes for younger children, with possible therapeutic implications. In providing an overall description of health, instruments like the CHQ may add another dimension to the care of children with diabetes and can feasibly be used within clinical settings.

Adolescent↗
PubMed1999

Pre-operative chemo-radiotherapy in locally advanced rectal cancer: is this the way of future management?

The purpose of the present paper was to update a prospective analysis (H Elsaleh et al. unpubl. data, 1997) investigating the effectiveness and toxicity of pre-operative pelvic radiotherapy with modest dose 5-fluorouracil (5-FU) in locally advanced rectal cancer (T3-T4). A total of 31 patients were assessed (28 T3 and three T4 tumours). Pre-operative pelvic radiotherapy was delivered in four fields, 45 Gy to the International Commission on Radiation Units and Measurements (ICRU) point in 25 fractions over 5 weeks. A radiosensitizing dose of 5-FU was delivered at 500 mg/m2 on days 1, 2 and 3, and days 22, 23 and 24. Mesorectal excision of the rectal tumour either by anterior or abdomino-perineal resection was planned at 4-6 weeks from completion of pre-operative treatment. Response to therapy was assessed by fresh macroscopic measurement of the surgical specimen. Patients had a low toxicity profile; an estimated 50% or greater response was seen in 24 out of 31 (two complete responses). There were no surgical difficulties achieving resection. No late complications were documented, although follow-up was short. In locally advanced rectal cancer, pre-operative chemo-radiotherapy had a low toxicity profile. Appropriately fractionated pre-operative chemo-radiotherapy is a reasonable option in this disease and should be further evaluated. The optimal method of delivery of the radiosensitizing agent (5-FU) is the subject of further investigation.

Adult↗
PubMed1998

Predicting the severity of radiation skin reactions in women with breast cancer.

PURPOSE/OBJECTIVES: To develop a method of predicting the severity of acute radiation skin reactions. DESIGN: Prospective, descriptive correlational with repeated measures. SETTING: Outpatient radiation oncology department in a metropolitan public teaching hospital in Western Australia. SAMPLE: 126 adult women aged 30-78 receiving postlumpectomy radiation therapy for breast cancer. METHODS: Data about potential predictive factors were collected during the first week of radiation. Weekly observations of the skin reaction using the Radiation Therapy Oncology Group scoring system were recorded throughout treatment with an inter-rater reliability of 0.85. RESULTS: Chi square analysis and t-tests revealed many factors related to severe skin reactions on a univariate level. Logistic regression analysis calculated the relative risk and probability of developing a severe skin reaction. Predictive factors included weight, breast size, lymphocele aspiration, smoking, age, skin cancer, tumor stage, and radiation dose. CONCLUSIONS: In addition to radiation dose, some factors that impair wound healing also contribute to the cause of patient-to-patient variation, thus making it possible to predict who is likely to develop a severe skin reaction. IMPLICATIONS FOR NURSING PRACTICE: The findings will assist in individualizing the assessment, education, and management of women undergoing radiation therapy for breast cancer. Further research could lead to the development of a method of risk assessment for skin reactions for use in radiation therapy nursing.

Adult↗
PubMed1994

Breast cancer in Western Australia in 1989: III. Accuracy of FNA cytology in diagnosis.

A population-based study of all cases of breast cancer diagnosed in Western Australia (WA) in 1989 revealed 701 cases of cancer in 692 women. Three hundred and ninety-six (56.5%) of these cancers had fine needle aspiration (FNA) cytology. Forty-three cases were managed non-surgically, on the basis of an FNA diagnosis and without histologic follow up. Of the cases with histological follow-up, 73% received an unequivocal diagnosis of malignancy by FNA, and abnormal cells (atypical, suspicious or malignant diagnoses) were reported in 94.2%. Of the cases, 3.2% were reported as benign and in 2.6% the samples taken were unsatisfactory. There were no false positive cytological diagnoses of malignancy. This study is the first to examine the results of FNA diagnosis of breast cancer from a medical community as a whole, rather than for individual or specialist units; the accuracy of diagnosis was similar for different pathology practices including public and private sector laboratories. Lower absolute sensitivity (the proportion of cases given an unequivocal diagnosis of malignancy) was seen in very small and very large tumours, pure duct carcinoma in situ (DCIS), and invasive lobular carcinoma. False negative rates (the proportion of cases given a benign cytological diagnosis) were very low for all laboratories (0-4.5%) and for all types of carcinoma, and the proportion of unsatisfactory samples was exceptionally low for all laboratories (0-4.5%). The overall figures for accuracy are similar to those reported from other centres in Australasia and overseas, and confirm the effective use of FNA cytology throughout the clinical and pathology community in WA.

Adenocarcinoma, Mucinous↗
PubMed1989

Maintenance chemotherapy in limited small cell lung cancer: a randomised controlled clinical trial.

In a prospective randomised study 68 patients with limited small cell bronchogenic carcinoma were assigned to induction treatment with combined alternating non-cross-resistant chemotherapy plus split course radiotherapy without (NM) or with (M) subsequent maintenance therapy. Induction chemotherapy consisted of cisplatinum and VP16213q. 3 weeks followed by cyclophosphamide, vincristine and methotrexate (CVM)q. 4 weeks. Three courses of this 7-week chemotherapy programme were given. Radiotherapy to the primary lesion of 25 Gy in 13 fractions was given after each of the first and second courses of chemotherapy. Those in complete remission following the induction phase received prophylactic cranial irradiation. Those assigned to maintenance received a further six cycles of CVM after induction. The overall survival of patients randomised to maintenance therapy was significantly inferior to that of those randomised to no maintenance therapy (median survival NM 19.2 vs M 14.1 months, P = 0.05 log rank). Among patients achieving a complete remission of disease on induction therapy those receiving maintenance also showed a trend towards inferior survival (median survival NM 26.8 vs 18.0 months, P = 0.06 log rank). Deaths in each group of patients were predominantly due to tumour progression. The results do not support the use of maintenance chemotherapy after the use of intensive combined therapy induction programmes in the management of limited small cell bronchogenic carcinoma.

Adult↗
PubMed1988

Transpapillary iridium-192 wire in the treatment of malignant bile duct obstruction.

Twenty four patients with malignant bile duct obstruction were treated with intraluminal radiotherapy using iridium-192 wire inserted through an endoscopically placed nasobiliary catheter. Biliary drainage after treatment was maintained by an endoprosthesis. The median dose of intraluminal radiotherapy was 6000 cGy; two patients with cholangiocarcinoma were given a second course because of disease extension; four patients with pancreatic carcinoma received additional external irradiation (3000 cGy). There was one early death from a cerebrovascular accident (30 day mortality, 4.2%). Cholangitis (30%) was the major early complication and stent blockage (40%) the major late complication; there were no complications directly attributable to radiotherapy. The median survival for patients with pancreatic carcinoma was 250 days and for cholangiocarcinoma, 300 days. This method is technically feasible and may prove safer than the transhepatic technique. The ability of intraluminal irradiation to improve palliation or lengthen survival in patients with malignant bile duct obstruction remains uncertain. Assessment by a prospective, controlled trial is essential.

Adenoma, Bile Duct↗
PubMed1985

Studies of peritoneal macrophage function in murine systemic lupus erythematosus. 2. Nature of elevated resident peritoneal cells in NZB and (NZB x NZW)F1 mice.

The numbers of resident peritoneal cells recovered from NZB and (NZB X NZW)F1 hybrid mice, which develop systemic lupus erythematosus (SLE), increased strikingly with age as compared with cells recovered from normal mice. The rise paralleled the onset of anti-DNA antibodies, occurring earlier in females than in males. The increased number of cells was due to an accumulation of medium-sized cells with an indeterminate appearance, but with the functional characteristics and cell markers typical of a macrophage. The unusual cells were esterase, F4/80 and Mac-1 positive, peroxidase, and Alcian blue negative, and were shown on sedimentation velocity separation to be phagocytic for EA and C3 (serum-treated) zymosan; 47-48% of peritoneal cells were Ia positive.

Age Factors↗
PubMed1983

Salivary gland dysfunction following radioactive iodine therapy.

Radioactive iodine is used extensively for the treatment of thyrotoxicosis and thyroid carcinoma. Iodine is actively taken up by the salivary glands and, following its use, salivary dysfunction may result as a consequence of radiation damage. The literature is reviewed and a case is reported in which a patient presented with a significant increase in caries rate attributed to salivary dysfunction following radioactive iodine therapy for a thyroid carcinoma.

Adult↗