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Biomedical subjects

B Jones

Publications and source records attributed to B Jones.

At least 235 records · Page 13Linked to original sources
PubMed1996

A modelled comparison of the effects of using different ways to compensate for missed treatment days in radiotherapy.

There is much evidence for the detrimental effect on tumour control of missed treatment days during radiotherapy, amounting for example to approximately a 1.6% absolute decrease in local control probability per day of treatment prolongation in the case of head and neck squamous cell cancer. Various methods to compensate for missed treatment days are compared quantitatively in this article, using the linear-quadratic formalism. The overall time and fraction size can be maintained by either treating on weekend days (the preferred way (Method 1a), although with unsocial hours and at extra cost) or using two fractions per day to "catch up' (Method 1b). The latter might incur a small loss of tolerance regarding late reactions, when intervals of 6-8 h are used rather than 24 h, and there may be logistical/scheduling difficulties with larger numbers of patients in some centres when using this method. A second type of strategy retains overall treatment time, and also one fraction per day, but the size of the dose per fraction is increased. For example, this may be done for the same number of "post-gap' days as gap days (Method 2). However, with this method, calculated isoeffect doses regarding late reactions indicate a probable decrease in tumour control rate (Method 2a). Otherwise, isoeffective doses regarding tumour control result in an increase in late reactions (Method 2b). In addition, this method is unsuitable for short regimens already using high doses per fraction. To reduce this problem, overall treatment time can also be retained by using fewer fractions, all of greater size in the case of planned gaps (statutory holidays), or larger remaining fractions after unplanned gaps (Method 2c). The problem also with this method is that equivalence for tumour control gives an increase in late reactions. The least satisfactory strategy (Method 3) is to accept the protraction caused by the missed treatment days, and give either the same prescribed number of (slightly larger) fractions or the planned treatment followed by one (or more) extra fraction to compensate for the gap. This would retain the expected local control rate, but there would be an increase in late reactions. An example of this, using average parameter values, is that a 3-day gap (necessitating four extra days to complete treatment with one fraction of 2.4 Gy) might maintain a 70% local control rate for glottic carcinoma, but severe reactions might rise from 1% to 4% and minor/moderate reactions from 37% to 50%. In this example, the inclusion of an extra weekend would increase the required extra dose and hence may further increase the morbidity rates. A final point is that the effect of treatment interruptions for an individual patient is expected to be greater than that for a group of patients because of interpatient heterogeneity tending to flatten dose-response curves. Calculations show that the above value of 1.6% loss of local control per day for a group of patients may reflect values for individual patients that range around a median value of as much as 5% per day, so stressing further the importance of gaps in treatment. It is concluded that, wherever possible, treatment days should not be missed. If they are missed, it is important to compensate for them, preferably by one of the first of the above methods (1a or 1b), in order to keep as close as possible to the original/standard prescription in terms of total dose, dose per fraction and overall time.

Brachytherapy↗
PubMed1996

Abnormal saccadic distractibility in patients with schizophrenia: a 99mTc-HMPAO SPET study.

Recent research has shown that some patients with schizophrenia have a severe impairment in the suppression of reflexive saccadic eye movements in the ANTI-saccade task. This saccadic distractibility has previously been found in patients with lesions of dorsolateral prefrontal cortex, implicating an abnormality of prefrontal cortex. The objective of the present study was to determine the contribution of these and other areas to the ANTI-saccadic abnormality in schizophrenia by functional neuroimaging. Using 99mtechnetium-HMPAO high resolution multidetector single-photon emission tomography, regional cerebral blood flow (rCBF) during performance of the ANTI-saccade eye-movement task was compared, by statistical parametric mapping, in ten male schizophrenic patients on stable antipsychotic medication who had a high distractibility error rate on the task, and eight similar patients who had normal distractibility error rates. Compared with the normal error group, the patients with high error rates showed significantly decreased rCBF bilaterally, in the anterior cingulate, insula, and in left striatum. These same patients also had increased perseverative errors on the Wisconsin Card Sort Test.

Adult↗
PubMed1996

Maladaptive coping and affective disorders among cancer patients.

Coping has attracted much attention in research as a possible mediator of the psychological impact of cancer. Yet, conceptual ambiguity and methodological limitations have resulted in weak and contradictory findings. A major shortcoming has been the use of designs which do not represent adequately the complexity or the diversity of demands which arise from the diagnosis and treatment of cancer. The neglect of appraisal in the assessment of the relationship between coping and mental health is of particular concern, given the role it has been found to play in the onset and maintenance of affective disorders. In a prospective study 673 newly diagnosed cancer patients were interviewed 4 to 8 weeks and 1 year later to assess the effects of their appraisals, coping responses and resolution of any concerns on subsequent mental health. Logistic regression analyses, adjusted for possible confounding variables, were used to investigate the relationships between coping variables and affective disorders. When examined separately the degree of threat appraised, the reporting of a helpless response and perceived success of primary responses in resolving concerns all predicted subsequent effective disorder. However, in a multivariate model only appraisal and success of the response in resolving the concern were significant. No response was found to prevent affective disorders, however certain types of responses were associated with the resolution of specific concerns. The results highlight the importance of assessing the whole coping process and the need to address the complex and multifaceted characteristics of cancer demands. On the basis of our findings we describe a maladaptive cycle of coping, which we believe contributes to the later onset of affective disorders in cancer patients.

Adaptation, Psychological↗
PubMed1996

Systemic anomalies in 77 patients with congenital anophthalmos or microphthalmos.

Congenital anophthalmos and microphthalmos are rare conditions which can have associated pathology in the second eye and/or systemic anomalies. A retrospective review of 77 patients with congenital anophthalmos or microphthalmos seen at Moorfields Eye Hospital over a 13 year period was performed. A detailed description of the ocular and systemic anomalies present in our series of patients is given, and the current understanding of the pathogenesis of congenital anophthalmos and microphthalmos is reviewed.

Abnormalities, Multiple↗
PubMed1996

Generalized immune activation in pulmonary tuberculosis: co-activation with HIV infection.

Parameters of immune activation/differentiation were studied in a group of newly diagnosed HIV- and HIV+ pulmonary tuberculosis (TB) patients. Compared with controls, HLA-DR expression on both CD4 and CD8 T cells from the HIV- TB patients was approximately doubled; HLA-DR on T cells from the HIV+ group was tripled. The monocytes from both groups of patients expressed abnormally high levels of the Fc gamma receptors I and III. Serum levels of tumour necrosis factor-alpha (TNF-alpha), neopterin and beta 2-microglobulin were increased in HIV- and even more so in HIV+ TB patients. The expression of HLA-DR on T cell subsets and of Fc gamma R on monocytes correlated with each other, but not with serum activation markers. This pattern of non-specific activation during TB infection may be associated with enhanced susceptibility to HIV infection.

Adult↗
PubMed1996

Age of onset in familial and sporadic schizophrenia.

We have studied the gender and family history differences with regard to age of onset of schizophrenia. These differences have often been viewed as an important clue to the aetiology of the illness. Patients from three centres in Europe and Canada were included in the study. A sample of 1089 subjects was categorized according to the subject's sex, family history of schizophrenia, and the centre. The principal statistical method was analysis of variance. Patients with no family history of schizophrenia had a consistently higher average age of onset. This effect was seen in both male and female subjects across all three groups. These results support the relationship between familial risk and early onset, but no interaction of gender and family history was found.

Adult↗
PubMed1996

A clinical and academic outcome study of children attending a day treatment program.

OBJECTIVE: To assess the behavioural and academic improvement of children who attended a day treatment program during a defined period of time. METHOD: Forty-six children admitted consecutively to the project were assessed on admission and discharge using behavioural and academic measures. They also had intelligence and language assessments. The subjects attended the program for one academic year, on the average. The large majority presented with disruptive behaviour disorders and low academic achievement levels. RESULTS: There was a significant improvement reported by the parents in externalizing (P < 0.001) and internalizing (P < 0.05) behaviour. The subjects also gained one academic year, but their levels continued to be low in terms of percentiles. Measures of academic improvement showed significant associations with cognitive measures only (subscales of Wechsler Intelligence Scale for Children-Revised [WISC-R] and Clinical Evaluation of Language Fundamentals-Revised [CELF-R]). CONCLUSION: A day treatment and school program is an effective modality for treatment and remediation of children with severe psychiatric disorders. The academic underachievement may be resistant to remediation within the limited period of attendance in such a program.

Adolescent↗
PubMed1996

Case report: low dose rate and high dose rate intracavitary brachytherapy in a patient with carcinoma of the cervix.

The role of low dose rate (LDR) intracavitary radiotherapy in the management of carcinoma of the uterine cervix is well established. However, there are selected groups of patients in whom high dose rate (HDR) intracavitary radiotherapy may have particular advantages. A case report of a patient with carcinoma of the cervix who received both LDR and HDR intracavitary radiotherapy is presented. A comparison of the normal tissue doses produced by the two forms of brachytherapy is made. The choice of dose for the HDR treatment was calculated using standard linear quadratic isoeffect equations. The relative clinical merits of LDR and HDR treatments in gynaecological cancer are discussed.

Brachytherapy↗
PubMed1996

Treatment of carcinomas of the uterine cervix which remain bulky after initial external beam radiotherapy: a pilot study using integrated cytotoxic chemotherapy prior to brachytherapy.

The use of cytotoxic chemotherapy (CT) between external beam radiotherapy (EBRT) and intracavitary brachytherapy (BT) in patients with bulky carcinomas of the uterine cervix which regress poorly after initial EBRT has been evaluated in a pilot study. The aim of CT was to limit tumour clonogen repopulation while awaiting further tumour regression in order to improve the BT dose distribution. Between 1989 and 1992, 22 patients with FIGO Stage IIA, IIB and IIIB cervical carcinomas were given two to three cycles of cisplatin-based CT between EBRT and intracavitary BT. Patients were selected for CT if there was bulky residual tumour extending beyond the range of point "A" after completion of EBRT. The median survival of patients with Stage IIA/B and Stage IIIB disease was 24 months and 13 months, respectively. The 5 year actuarial survival rate for patients with Stage IIA/B disease was 42%. There were no long-term survivors among patients with Stage IIIB disease. Survival difference between Stage IIA/B patients and Stage IIIB patients was statistically significant (p < 0.04). 5 year actuarial pelvic control rates were 38% and 0% for Stage IIA/B and Stage IIIB patients, respectively. There were no serious late radiation complications in the entire study group. Bulky carcinomas of the cervix which respond poorly to initial EBRT have a particularly poor prognosis. For Stage IB-IIB patients with persistent bulky disease after EBRT, published reports suggest that a 5 year actuarial survival rate of around 40% can be obtained using higher doses of radiation alone, but the risk of serious late morbidity is considerable. The results of our study suggest that in Stage IIA/B carcinomas of the cervix which remain bulky after initial EBRT, the use of integrated cytotoxic chemotherapy prior to intracavitary BT can give similar 5 year survival rates but with minimal treatment related morbidity.

Adenocarcinoma↗
PubMed1996

The influence of air cavities on the optic chiasm dose during pituitary radiotherapy for acromegaly.

The treatment planning of acromegalic patients can be complicated by the presence of abnormally large frontal air sinuses which allow increased anterior beam transmission causing increased dose to the optic nerve and chiasm which, if excessive, can result in blindness. This potential problem has been investigated by computer treatment planning exercises which have allowed for a variable thickness (1-3 cm) of air cavity beneath the frontal field and for different weightings of the lateral opposed fields relative to the anterior field. The resultant overdosage can be greater than 5% of the intended dose. The increased biological effect from errors of this magnitude is sufficient to increase the risk of optic nerve damage since neural tissue is very sensitive to small increments in fraction size. Even when the reduced attenuation is allowed for in the computer plan, the thickness of the air sinuses varies across the field so that irradiation through the frontal enlarged frontal air sinuses causes inhomogeneous dose distributions in the target volume. Acromegalic patients should therefore be treated with a more superior beam which would avoid the air sinuses altogether.

Acromegaly↗
PubMed1996

The reduction of tumour control with increasing overall time: mathematical considerations.

The rate of loss of tumour control (dP/dt) with extension of treatment time is analysed to assess the relative contributions of radiobiological parameters (radiosensitivity, clonogen doubling time, clonogen numbers and fractionation schedule) on such loss. Linear quadratic modelling and Poisson statistics are used to study individual tumour responses. A heterogeneous tumour population is constructed by the use of random sampling techniques to allow for variations in intrinsic radiosensitivity and clonogen doubling times. Average tumour control probability is calculated for this population for two different fractionation schedules (60 Gy in 30 fractions and 50 Gy in 15 fractions), each given over 15-60 days. The magnitude of dP/dt will depend upon the tumour cure probability (P): the loss of control will be most significant for tumours which have a cure of 37% when the Poisson survival model is used. The analysis suggests that compensation for short unscheduled treatment gaps (e.g. by increasing the total dose or rescheduling with use of weekend treatment sessions) may only be required for difficult tumours (i.e. radioresistant and/or with short clonogen doubling times). Where pre-treatment clonogen numbers are relatively low as in small volume tumours or after surgical debulking, the model predicts that correction for short treatment gaps is probably not required if the average effective clonogen doubling times are longer than 5 days. Different dose-time-fractionation schedules, even though producing similar overall cure rates in clinical practice, may actually be achieving cures in different subpopulations within a population of tumours, since the value of dP/dt in each individual tumour will depend upon the set of radiobiological parameters given above. For a hypothetical randomly selected heterogeneous tumour population the predicted rates of loss of tumour control produced by an extension in treatment time are 0.9 and 1.1% per day, respectively, for the above fractionation schedules. These values are close to those reported in the clinical literature for the first 2 weeks of treatment prolongation (1-2% per day for squamous cell carcinomas). The Poisson method, when combined with random sampling techniques, consequently provides realistic data. Modelling of this clinical problem provides an insight into how tumour sub-populations, each characterized by its own set of radiobiological parameters, can influence the overall rate of loss of tumour control in a heterogeneous population. Random sampling techniques should be considered as necessary precursors for the assessment of the choices of dose-fractionation in future clinical trials particularly when more precise data regarding the radiobiological parameters and their statistical variations become available.

Humans↗
PubMed1996

Bladder dose estimation during intracavitary brachytherapy for carcinoma of the cervix using a single line source system.

The estimation of maximum bladder doses from orthogonal radiographs is unreliable when triple source systems are used for intracavitary brachytherapy (BT) for gynaecological cancers. For single line source systems, the estimation of maximum bladder doses from radiographs should be more reliable due to the radial symmetry of the isodose distribution. A pilot study has been carried out to compare the estimated maximum bladder doses from standard radiographs with data obtained from CT for single line source BT treatments. 12 patients undergoing treatment for carcinoma of the cervix were selected for CT assessment of their bladder doses. For each patient, the dose rates at the International Commission of Radiation Units and Measurements (ICRU) bladder reference point B1 and a second reference point B2 2.5 cm cranially were computed from orthogonal radiographs and were compared with the maximum bladder dose rate as determined by CT scanning. Dose rates were computed for two different source loading patterns: (1) a 6 cm line source with uniformly distributed linear activity along its length; (2) a 6 cm line source with increased activity in the central 2 cm segment. The mean ratio of the maximum CT bladder dose rate to the dose rate at the ICRU reference point B1 on orthogonal radiographs for the line source with uniform linear activity was 1.32 (range 0.62-2.43, SD = 0.54). When the dose rates at both reference points B1 and B2 were considered, the mean ratio of the maximum CT dose rate to the maximum dose rate from radiographs was only 1.05 (range 0.72-1.72, SD = 0.24). For the line source with increased activity in the central segment, the mean ratio of the maximum CT bladder dose rate to the dose rate at B1 was 1.38 (range 0.60-2.63, SD = 0.64). When both B1 and B2 were considered, the variation in the ratio of the maximum CT dose rate to the maximum dose rate from radiographs was considerably smaller (mean ratio = 1.07, range 0.69-1.76, SD = 0.26). For single line source systems, single point dose estimation using the ICRU reference point on orthogonal radiographs will underestimate the maximum bladder dose although the discrepancy is less than for triple source systems. If the ICRU reference point is used in conjunction with a second reference point 2.5 cm cranially, then underestimation of the maximum bladder dose is unlikely to occur as at least one of the points is likely to be a reasonable estimate of the maximum bladder dose.

Brachytherapy↗
PubMed1996

Hyaluronan turnover in the synovial fluid in metacarpophalangeal--and middle carpal joints in standardbred horses.

The biological turnover of hyaluronan (sodium hyaluronate) of different molecular weights (0.6 x 10(6) and 2.5 x 10(6) Daltons) was studied in the synovial fluid of the middle carpal and metacarpophalangeal joints of 6 clinically healthy Standardbred horses. The hyaluronan was radioactively labelled with 14C. The biological half-life (t1/2) was calculated from repeated synovial samples after injection of the labelled hyaluronan. The mean t1/2 in the metacarpophalangeal joints was 9.7 h for low molecular weight hyaluronan and 8.9 h for high molecular weight hyaluronan and in the middle carpal joints 16.0 h and 12.5 h respectively. These was no significant difference in turnover of the different molecular weights of hyaluronan.

Animals↗