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Biomedical subjects

R Allison

Publications and source records attributed to R Allison.

At least 19 recordsLinked to original sources

Myeloablative allogeneic stem cell transplantation for advanced stage multiple myeloma: very long-term follow up of a single center experience.

We aimed to review the long-term outcome of myeloablative allogeneic stem cell transplantation (SCT) performed for multiple myeloma (MM) at our institution. Records of all patients who received standard myeloablative allogeneic SCT for MM were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS), and event-free survival (EFS) were calculated using the Kaplan-Meier method. In total 37 transplants had been performed. Median follow up post-SCT was 108 months (range: 33-148). The majority of patients suffered advanced stage disease and/or had received multiple prior therapies prior to SCT. Transplant-related mortality (TRM) at 100 days was 32%. Grades 2-4 acute graft-vs.-host disease (GVHD) occurred in 18 patients (49%), and extensive stage chronic GVHD in seven (28%) of 25 patients surviving greater than day 100. Median OS, PFS, and EFS were 28 months, 66 months and 13 months, respectively, with 5 year OS, PFS, and EFS 40%, 54% and 24%. Our results suggest that allogeneic SCT, even when performed in advanced stage, heavily pretreated MM, still results in long-term EFS in a significant minority of patients. Efforts should continue on alternative allogeneic SCT approaches to reduce the high early TRM rate associated with myeloablative conditioning.

Adult↗

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↗

The effect of a diet containing excess quickly degradable nitrogen (QDN) on reproductive and metabolic hormonal profiles of lactating dairy cows.

The objective of this experiment was to examine the effects of an excess intake of quickly degradable nitrogen (QDN) on metabolic and reproductive parameters in lactating dairy cows. Twenty-two lactating dairy cows were fed a total mixed ration once daily. The control diet was a typical ration for high producing cows in the UK (CP = 17.5%, ME = 11.8 MJ/kg DM). The cows were randomly divided into two groups, control diet (control; n = 12) and excess QDN diet (QDN; n = 10). The QDN group was fed an additional 250 g of urea per cow per day, from 10 days before insemination (day 0) until the end of the experiment, 17 days after the second insemination. Ten days before insemination, a synchronized oestrus was induced and the cows inseminated twice, 48 and 72 h after synchronization, with commercial frozen semen from a single sire. Ovaries were scanned using B-mode ultrasonography 10 days before insemination and then daily from 3 days before insemination. Eighteen of the cows (9 control and 9 QDN) were sampled more intensively to determine the pulsatile pattern of secretion of luteinizing hormone (LH) and growth hormone (GH). Cows were slaughtered 17 days after insemination, the reproductive tracts recovered and flushed to retrieve embryos. The excess QDN diet resulted in elevated (P < 0.05) plasma urea concentrations 3 days after starting urea feeding and these were maintained until the end of the experiment. However, the excess QDN diet did not significantly affect daily milk production or plasma concentrations of insulin and IGF-I. The QDN treatment did not significantly affect pulsatile patterns of secretion of LH and GH or the number of small (< 0.5 cm diameter) and medium to large follicles (> 0.5 cm diameter). Twenty cows ovulated following synchronization (control 11/12; QDN 9/10). There were no significant differences between the control and the QDN groups in the peak concentrations of oestradiol during the follicular phase or in the post-ovulatory pattern of plasma and milk progesterone secretion. Embryos and/or foetal membranes were recovered from 10 cows (5 control and 5 QDN). The results of the current study show that feeding excess QDN, as urea, for 27 days commencing 10 days before insemination had no effect on reproductive or metabolic hormonal parameters. Ovulation and the formation and function of the post-ovulatory corpus luteum were also unaffected by excess QDN. These data suggest that the harmful effects of excess intakes of QDN on fertility occur after 17 days following ovulation.

Animals↗

Cytokine profiles in patients receiving wide-field + prostate boost radiotherapy (xRT) for adenocarcinoma of the prostate.

As a result of the association between ionizing irradiation and the induction of inflammatory and fibrogenic cytokines, circulating levels of IL-1alpha, macrophage colony stimulating factor (M-CSF) and TGFbeta were measured in a group of 37 patients who presented with well-defined adenocarcinoma of the prostate and were treated with wide-field pelvic (WFP) + prostate boost (PB) radiotherapy (xRT) according to RTOG protocols 94-08 and 94-13. First and foremost, patients with prostate cancer (PC) were found to have a significantly (p<0.05) elevated plasma level of the three cytokines prior to treatment. Moreover, during WFP + PB xRT, these circulating cytokine levels were further elevated, the elevation occurring in the form of cyclic waves; the concurrent waves of elevated IL-1alpha and M-CSF preceding that of TGFbeta. In addition to providing support for the existence of a humoral response to xRT in patients receiving WFP + PB xRT, the data demonstrated a significant correlation between the integral radiation dose (ID) and the temporal expression and magnitude of plasma IL-1alpha, M-CSF and TGFbeta levels in patients that had received 1-5 fractions (1.8-9Gy) of WFP + PB xRT. Thereafter, the appearance of elevated waves of cytokine expression in the patient's plasma continued independent of additional fractions of WFP + PB xRT.

Adenocarcinoma↗

A comparative analysis: storm water pollution policy in California, USA and Victoria, Australia.

Urban drainage systems historically were developed on principles of hydraulic capacity for the transport of storm water to reduce the risk of flooding. However, with urbanization the percent of impervious surfaces increases dramatically resulting in increased flood volumes, peak discharge rates, velocities and duration, and a significant increase in pollutant loads. Storm water and urban runoff are the leading causes of the impairment of receiving waters and their beneficial uses in Australia and the United States today. Strict environmental and technology controls on wastewater treatment facilities and industry for more than three decades have ensured that these sources are less significant today as the cause of impairment of receiving waters. This paper compares the approach undertaken by the Environmental Protection Authority Victoria for the Melbourne metropolitan area with the approach implemented by the California Environmental Protection Agency for the Los Angeles area to control storm water pollution. Both these communities are largely similar in population size and the extent of urbanization. The authors present an analysis of the different approaches contrasting Australia with the USA, comment on their comparative success, and discuss the relevance of the two experiences for developed and developing nations in the context of environmental policy making to control storm water and urban runoff pollution.

California↗

153Sm EDTMP for bone marrow ablation prior to stem cell transplantation for haematological malignancies.

This study examined the safety of adding 153Sm lexidronam to standard conditioning regimens in patients undergoing stem cell transplantation for marrow based haematological malignancies in whom total-body irradiation as part of conditioning was desirable but not feasible. Ten such patients were enrolled, seven with multiple myeloma. An escalating regimen of 19-45 GBq of 153Sm lexidronam was added 12-14 days prior to the standard transplantation regimen. Evaluation parameters included time to engraftment, status at day +100 by International Bone Marrow Transplant Registry (IBMTR) criteria and toxicity during this period. Absorbed marrow radiation doses were estimated using the MIRDOSE 3 program. No adverse events were attributable to 153Sm lexidronam. Of the seven patients with multiple myeloma, four achieved complete response, two partial response, and another had stable monoclonal band at 3 months post-transplant. One patient with Refractory Anaemic with Excess Blasts in transformation (RAEBt) died of a presumed fungal infection, whilst another with acute myeloid leukaemia relapsed, dying at day +153. A patient with low-grade lymphoma showed no evidence of residual disease at day +100. The total marrow absorbed dose was estimated to be 0.7+/-0.2 mGy x MBq(-1). Regional uptake was markedly non-uniform with poor uptake in the appendicular skeleton. Dose-limiting toxicity was not attained. At the activities used 153Sm lexidronam was not associated with additional toxicity in this population. Adequate absorbed radiation dose to appendicular marrow is unlikely to be deliverable by this approach alone.

Adult↗

A dynamic model of N metabolism in the lactating dairy cow and an assessment of impact of N excretion on the environment.

Improving N utilization in dairy cows and especially reducing N output in excreta is desirable due to global concerns of agricultural contribution of N to environmental pollution, particularly as ammonia. Data from five N balance experiments were used to develop a dynamic model that was evaluated with independent data. Model predictions of feces, urine, and milk outputs were close to observed values. Statistical analysis showed that 96% of mean square prediction error for feces and urine N output predictions was due to random variation. However, the model tends to overpredict milk N output, especially at higher N intake levels. Evaluation of model predictions for independent experimental observations from Agricultural Development Advisory Service at Bridgets (U.K.) showed good agreement between predicted and observed urine N output (95% due to random variation). However, there was a slight underprediction for fecal N output (14% mean square prediction error due to bias) and overprediction of milk N output (22% of mean square prediction error due to bias). The model predictions of N outputs in excreta were sensitive to changes in energy concentration of the diet. Dietary protein degradability had only a small influence on predicted fecal N output. However, the model was sensitive in its predictions of urine N when protein degradability was varied. Application of the model to assess reduction in ammonia emissions from dairy cows showed that increasing the energy concentration could potentially reduce ammonia emissions by up to 25% per cow. Similarly, reducing CP concentration in the diet to about 16% could reduce ammonia production by 20% and lower degradability of CP to match microbial requirement by 19% per cow. The model is a first step toward a mechanistic approach of nutrient modeling, and it is a valuable method for predicting N excretions and estimating N emissions from dairy systems.

Ammonia↗

Photodynamic therapy for chest wall progression from breast carcinoma is an underutilized treatment modality.

BACKGROUND: Chest wall progression of breast carcinoma after failure of salvage surgery, radiation, and chemohormonal therapy is a quagmire with limited therapeutic options. Because photodynamic therapy (PDT) offers excellent results in cutaneous lesions, PDT may play a role in this indication. However, to the authors' knowledge, published data for this subgroup of patients using the only commercially available photosensitizing agent, Photofrin, often show high treatment morbidity, limiting PDT's usefulness. The authors report the feasibility of decreasing the photosensitizer drug dose as a means of exploiting photobleaching kinetics to improve the therapeutic ratio for these individuals. METHODS: One hundred two chest wall sites were treated with PDT after failure of multimodality salvage therapy. In these 9 patients, lesion size ranged from 0.57 to 9 cm. Photodynamic therapy consisted of outpatient intravenous infusion of 0.8 mg/kg of Photofrin, followed 48 hours later by 630 nm light treatment of 135-170 J/cm2 delivered by a KTP:YAG laser coupled to dye unit. Two patients underwent a second PDT procedure due to new lesion formation. All patients were observed for a minimum of 6 months, and none was lost to follow-up. RESULTS: Photodynamic therapy was well tolerated with no photosensitivity reported. Despite all patients having failed surgery, full dose radiation and multiagent chemohormonal therapy, chest wall lesions healed with no scarring. Only 1 (9 cm) lesion took longer than 3 months to granulate over. The authors were able to evaluate all treatment sites, and complete response, defined as total lesion elimination, was noted in 89% of the lesions; reduction without regrowth occurred in 8% with no response in 3% of the lesions. CONCLUSIONS: Despite having prior treatment and fragile tissues, low dose Photofrin-induced PDT offers excellent clinical response with minimal morbidity. These results show that PDT should play an important role in the management of chest wall failure from breast carcinoma.

Adult↗

Effects of dietary cholesterol restriction in a feline model of Niemann-Pick type C disease.

A feline model of Niemann-Pick disease type C (NPC) was employed to evaluate the effect of dietary cholesterol restriction on progression of disease. Two NPC-affected treated cats were fed a cholesterol-restricted diet beginning at 8 weeks of age; the cats remained on the diet for 150 and 270 days respectively. The study goal was to lower the amount of low density lipoprotein (LDL) available to cells, hypothetically reducing subsequent lysosomal accumulation of unesterified cholesterol and other lipids. Neurological progression of disease was not altered and dietary cholesterol restriction did not significantly decrease storage in NPC-affected treated cats. One NPC-affected treated cat had decreased serum alkaline phosphatase activity (ALP) and decreased serum cholesterol concentration. Liver lipid concentrations of unesterified cholesterol, cholesterol ester and phospholipids in NPC-affected treated cats were similar to those seen in NPC-affected untreated cats. Ganglioside concentrations in the NPC-affected treated cats and NPC-affected untreated cats were similar. Histological findings in liver sections from NPC-affected treated cats showed a diffuse uniform microvacuolar pattern within hepatocytes and Kupffer cells, in contrast to a heterogeneous macro/microvacuolar pattern and prominent nodular fibrosis in NPC-affected untreated cats. Similar differences in vacuolar patterns were seen in splenic macrophages. Although some hepatic parameters were modified, dietary cholesterol restriction did not appear to alter disease progression in NPC-affected kittens.

Alanine Transaminase↗

Spinal cord dose is higher than expected in head and neck radiation.

Myelopathy is a feared consequence of radiation therapy. Risk factors are multifocal; therefore, total dose calculation is crucial. We evaluated the contribution of scatter radiation to obtain an accurate cumulative spinal cord dose. Twenty patients undergoing three field head and neck radiation by Cobalt or 6 MV Linac had a total cord dose calculated from direct and scatter radiation. The cord was removed from the radiation field at tumor doses no higher than 4,400 cGy. Total tumor dose ranged from 5,400-7,400 cGy (mean 6060). All patients achieved the prescribed dose and none were lost to follow up (mean 36 months). It was found that scatter radiation can contribute as much as 20% extra dose to the spinal cord. Mean extra dose was 9% (range 1%-20%). This additional dose ranged from 52-810 cGy (mean 339 cGy). No apparent difference was seen with Cobalt or Linac source. Our conclusion was that significant additional dose is delivered to the spinal cord by scatter radiation and that scatter may contribute more to the development of myelopathy than previously believed.

Cobalt Radioisotopes↗

Tuberculous meningitis in a five-week-old infant.

We present the case of a five-week-old infant with tuberculous meningitis. The contact investigation and a review of the literature helped us differentiate congenital from acquired tuberculous meningitis. Though rare, we with to emphasize the importance of considering tuberculosis in any neonate with meningitis that fails to respond to conventional treatment, particularly in infants living in an environment where tuberculosis is prevalent.

Contact Tracing↗

Suicide rate following attendance at an accident and emergency department with deliberate self harm.

OBJECTIVE: To determine the risk of suicide in patients attending an accident and emergency (A&E) department with deliberate self harm. METHODS: Information was obtained on suicides and open verdicts from the coroner's office and cross checked with computerised records in the A&E department. RESULTS: There was a trend to suicide among younger socially isolated males and older females. CONCLUSIONS: There is a significant association between suicide and a previous attendance at A&E with deliberate self harm. Appropriate assessment of these patients is an efficient way of managing self harm.

Adult↗

Conservative therapy of breast cancer in Queensland.

PURPOSE: Primary radiation therapy following breast-conserving surgery has been an accepted alternative to mastectomy in Europe and North America for many years. In Australia, however, the history of breast conservation for early invasive breast cancer is much shorter. The purpose of this study was to evaluate the results of breast conservation in a state-wide Australian radiotherapy service. METHODS AND MATERIALS: Between January 1982 and December 1989, 512 patients were treated with primary radiation therapy after breast conserving surgery. This analysis is based on a review of these patients, all of whom had Stage I or II breast cancer. RESULTS: With a median follow-up of 50 months, the 5-year actuarial rate of overall survival was 84% and disease-free survival was 80%. There have been 22 isolated local recurrences in the breast. The time to an isolated breast recurrence ranged from 12 to 83 months (median, 26 months). The 5-year actuarial rate of an isolated breast recurrence was 4%. The recurrence rate was higher for patients with involved margins (15% vs. 2%, p < 0.01). Local recurrence was also more likely in the presence of extensive ductal carcinoma in situ (DCIS), as opposed to no extensive DCIS (10% vs. 2%, p < 0.01). CONCLUSION: These results affirm that primary radiation therapy after breast conserving surgery in Queensland, has been given with a low rate of local recurrence, comparable to that obtained in other centers.

Actuarial Analysis↗

CNS germinomas: curable tumours in two adolescents.

Two cases of central nervous system germinoma are described which highlight the various presentations of this tumour in different anatomical locations. The first case is that of a 15 year old boy with a suprasellar germinoma who presented with the classical triad of diabetes insipidus, visual disturbance and hypopituitarism. The need for full hormonal evaluation and replacement therapy is stressed. In the second case a 14 year old boy with pineal germinoma presented with features of raised intracranial pressure, Parinaud's syndrome and normal anterior pituitary function. Both cases were treated with corticospinal irradiation which resulted in regression of the tumours. Follow up has now been for over 4 years with no sign of recurrence.

Adolescent↗

High dose-rate intraluminal irradiation in bronchogenic carcinoma. Technique and results.

Patients who present with symptomatic airway obstruction often have limited therapeutic options. Intraluminal irradiation has been used in an attempt to obtain sustained palliation. Patients treated with high dose-rate endobronchial irradiation have shown good to excellent palliation of symptoms, as well as a high rate of local control; however, these results have not always been devoid of complications. Some recent reports have shown a high incidence of morbidity, including an excessive incidence of fatal pulmonary hemorrhage. In this series, we report on 80 high dose-rate endobronchial treatments in 32 patients who were treated with remote afterloading endobronchial irradiation. All patients had endoscopic and histologic proof of tumor. Patients were divided into two groups. Group 1 consisted of 17 patients who were treated with endobronchial brachytherapy as a boost to primary external-beam irradiation. The remaining 15 patients comprised group 2 and were treated for endobronchial recurrence after prior irradiation with an external beam (main dose, 5,000 cGy). The endobronchial irradiation treatments were delivered using a high dose-rate remote afterloader. The standard dose per fraction was 500 cGy prescribed at a distance of 1 cm from the central axis of the catheter for a median of 3 fractions at weekly intervals. Treatment length averaged 5 cm; the median total dose was 1,500 cGy. The median follow-up for the entire group was 9.3 months, with a range of 6 to 24 months. Symptomatic improvement was attained in 15 of 15 patients presenting with hemoptysis, in 6 of 7 of those with cough, and in 10 of 10 who presented with dyspnea. In ten patients, follow-up endoscopy was performed, which revealed a pathologic complete response (by negative results on biopsies). At 6 months past the last brachytherapy, clinical and radiographic local control was obtained in 15/17 (88 percent) of the patients in group 1 and in 70 percent of the patients in group 2. All patients tolerated treatment well, without any acute or late complications, and there were no instances of fistula formation or fatal pulmonary hemorrhage. There was no association between the location of recurrence and complications. Fractionation, dose per fraction, and total combined dose appear to be important parameters in reducing complications.

Brachytherapy↗