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Biomedical subjects

C MacLeod

Publications and source records attributed to C MacLeod.

At least 19 recordsLinked to original sources
PubMed2002

The Child Protection Register: a tool in the accident and emergency department?

AIMS: To determine the number of children on the Child Protection Register (CPR) attending the accident and emergency (A&E) department and the referral source, diagnostic category, and frequency distribution for such attendances. To determine whether lack of knowledge that a child is on the CPR results in failure to suspect non-accidental injury (NAI) if the standard indicators of NAI have been sought. METHODS: Access to the CPR was obtained. Records of each child attending the A&E departments of the United Hospitals Trust between June 1994 and May 2000 were reviewed. RESULTS: Over the six years 191 children were on the CPR. Seventy nine (41%) attended A&E departments on 206 occasions. Frequency of attendance ranged to 18 with a mean of 2.6. Self referral was the commonest source of referral (81%) followed by general practitioners (13%), 999 calls (5%), and a small number from schools (1%). Most presentations involved trauma-upper limb (21%), lower limb (14%), and head injury (8%). Almost all cases of trauma were adjudged to be consistent with the history and NAI not suspected. Common childhood illnesses accounted for the remainder of presentations. Only six children were identified as being on the CPR at the time of presentation. Concerns were raised in two other cases and concerns should have been raised in three other children. Social Services were alerted on five occasions directly by the parents themselves. CONCLUSIONS: It is concluded that in the absence of knowledge of the status of a child on the CPR attending the A&E department, that screening for the standard indicators of NAI is adequate to detect most cases of NAI.

Child↗
PubMed2001

Lipopolysaccharide-induced apoptosis of macrophages determines the up-regulation of concentrative nucleoside transporters Cnt1 and Cnt2 through tumor necrosis factor-alpha-dependent and -independent mechanisms.

In murine bone marrow macrophages, lipopolysaccharide (LPS) induces apoptosis through the autocrine production of tumor necrosis factor-alpha (TNF-alpha), as demonstrated by the fact that macrophages from TNF-alpha receptor I knock-out mice did not undergo early apoptosis. In these conditions LPS up-regulated the two concentrative high affinity nucleoside transporters here shown to be expressed in murine bone marrow macrophages, concentrative nucleoside transporter (CNT) 1 and 2, in a rapid manner that is nevertheless consistent with the de novo synthesis of carrier proteins. This effect was not dependent on the presence of macrophage colony-stimulating factor, although LPS blocked the macrophage colony-stimulating factor-mediated up-regulation of the equilibrative nucleoside transport system es. TNF-alpha mimicked the regulatory response of nucleoside transporters triggered by LPS, but macrophages isolated from TNF-alpha receptor I knock-out mice similarly up-regulated nucleoside transport after LPS treatment. Although NO is produced by macrophages after LPS treatment, NO is not involved in these regulatory responses because LPS up-regulated CNT1 and CNT2 transport activity and expression in macrophages from inducible nitric oxide synthase and cationic amino acid transporter (CAT) 2 knock-out mice, both of which lack inducible nitric oxide synthesis. These data indicate that the early proapoptotic responses of macrophages, involving the up-regulation of CNT transporters, follow redundant regulatory pathways in which TNF-alpha-dependent- and -independent mechanisms are involved. These observations also support a role for CNT transporters in determining extracellular nucleoside availability and modulating macrophage apoptosis.

Animals↗
PubMed2001

Australian high-dose-rate brachytherapy protocols for gynaecological malignancy.

There is no consensus over the optimal dose fractionation schedules for high-dose-rate (HDR) brachytherapy used for gynaecological malignancy. In Australian public hospital departments of radiation oncology, HDR brachytherapy for gynaecological cancer is being more commonly used. A survey of public departments that are using this technology, or that plan to introduce this technology, was performed. Their current protocols are presented. In general, protocols are similar biologically; however, the practical aspects such as the number of fractions given do vary and may reflect resource restrictions or, alternatively, differences in interpretations of the literature and of the best protocols by clinicians.

Australia↗
PubMed2001

Locally advanced cervix cancer: chemotherapy prior to definitive surgery or radiotherapy. A single institutional experience.

Primary or neoadjuvant chemotherapy prior to definitive local therapy has potential advantages for locally advanced cervix cancer. It can downstage a cancer and allow definitive local therapy to be technically possible (surgery), or potentially more effective (radiotherapy). It can also eradicate subclinical systemic metastases. This report reviews a single institution's experience of neoadjuvant chemotherapy prior to definitive local therapy for cervix cancer over a 13-year period. One hundred and six patients were treated with this intent. The patients were analysed for their response to chemotherapy, treatment received, survival, relapse and toxicity. The chemotherapy was feasible and the majority of patients had a complete or partial response (58.5%). Eight patients did not proceed to local treatment. Forty-six patients had definitive surgery and 52 had definitive radiotherapy. The 5-year overall survival was 27% and the majority of patients died with disease. The first site of relapse was usually in the pelvis (46.2%). Late complications that required ongoing medical therapy (n=6) or surgical intervention (n=2) were recorded in eight patients (7.5%). On univariate analysis stage (P=0.04), tumour size (P=0.01), lymph node status (P=0.003), response to chemotherapy (P=0.045) and treatment (P=0.003) were all significant predictors of survival. On multivariate analysis, tumour size (P < 0.0001) and nodal status (P=0.02) were significant predictors of survival. Despite the impressive responses to chemotherapy of advanced cervix cancer, there is evidence from randomized trials that it does not improve or compromise survival prior to radiotherapy. As its role prior to surgery remains unclear, it should not be used in this setting outside a prospective randomized trial.

Adult↗
PubMed2000

Radiation treatment in recurrent squamous cell cancer of the vulva.

PURPOSE: To evaluate the treatment and outcome of recurrent vulvar cancer. METHODS AND MATERIALS: In a retrospective review of 26 women referred to the department of radiation oncology between 1982 and 1995, patient records were analyzed with respect to the findings at original surgery, the time to locoregional recurrence, the location of the recurrence, and the subsequent management and outcome. RESULTS: Sixteen recurrences were managed with a combination of surgery and radiotherapy, and the remainder with radiation treatment, combined with chemotherapy in some cases. The overall survival for the entire cohort at 5 years was 22%. The 5-year survival for those with recurrence confined to the vulva (n = 13) was 46%, compared with 0% for those women with a recurrence located or extending beyond the vulva (p = 0.002). The local control rate was 34.6%. CONCLUSION: Our results confirm the poor overall prognosis for this condition. In particular, they highlight the importance of the location of the recurrence as a prognostic indicator. Based on this review, we conclude that radiotherapy fields should encompass the region at risk if the intent is curative. Finally, low-dose palliation for groin node recurrence is ineffectual.

Adult↗
PubMed1999

Accelerated hyperfractionated radiotherapy for locally advanced cervix cancer.

PURPOSE: A phase II trial was designed to evaluate the toxicity and outcome of patients with locally advanced cervix cancer treated with accelerated hyperfractionated radiotherapy (AHFX). METHODS AND MATERIALS: In this prospective trial, AHFX doses of 1.25 Gy were administered twice daily at least 6 hours apart to a total pelvic dose of 57.5 Gy. A booster dose was then administered via either low-dose rate brachytherapy or external beam therapy to a smaller volume. All patients were accrued and treated at Peter MacCallum Cancer Institute (PMCI) between 1986 until April 1991. RESULTS: Sixty-one eligible patients were enrolled in this protocol; 2 (3.2%) had Stage IIB; 42 (68.9%) had Stage III; 8 (13.1%) had Stage IV and 9 (14.8%) had recurrent cervical cancer. Fifty-two patients (85%) completed the planned external beam without a treatment break. Thirty patients had acute toxicity that required regular medication. One patient died of acute treatment related toxicity. Fifty-five patients received booster therapy: 45 with intrauterine brachytherapy, 6 with interstitial brachtherapy, and 4 with external beam. The median follow-up of surviving patients was 6 years. Overall 5-year survival is 27% and 5-year relapse free survival is 36%. Nineteen patients died with pelvic disease and the actuarial local control rate was 66%. There were 8 severe late complications observed in 7 patients. Seven required surgical intervention (an actuarial rate of 27%). Five patients also required total hip replacement. CONCLUSIONS: The local control rate was favorable compared with other series that have used standard fractionation, although overall survival remained similar. The severe late complication rate was high for this protocol and higher than similar protocols reported in the literature.

Adenocarcinoma↗
PubMed1999

Whole abdominal radiotherapy following second-look laparotomy for ovarian carcinoma.

AIM: The safety and efficacy of whole abdominal radiotherapy was evaluated as salvage or consolidation treatment for ovarian cancer patients treated with primary surgery and chemotherapy, followed by second-look laparotomy (SLL). Overall survival and acute and late toxicity of treated patients were assessed. METHODS: Patients were recruited between April 1981 and June 1994. All patients had SLL performed at Royal Prince Alfred Hospital after completion of primary chemotherapy. Data collected included demographic details, diagnosis, tumor stage, histology, grade, adjuvant chemotherapy, and radiotherapy. Radiation dose and fractionation, field size, boost volume and dose, failure to complete treatment and treatment interruptions, renal dose, and acute and late toxicity were recorded. RESULTS: Fifty-one patients were evaluated; the median age was 51 years. Median follow-up for patients still alive was 62 months. Prior to 1988, chemotherapy comprised oral chlorambucil, with or without cisplatin (n = 25), while after this date all patients (n = 26) received primary cisplatin-based therapy. A radiation dose of 22. 5 Gy over 22 fractions was planned to the whole abdomen followed by a pelvic boost of 22 Gy in 11 fractions. Radiotherapy was completed in 37 (73%) patients. Treatment interruptions were necessary in 12 (24%) patients. Thrombocytopenia, neutropenia, nausea, vomiting, and diarrhea were the main causes of incomplete or interrupted treatment. Late bowel toxicity was seen in 6 (12%) patients, 2 of whom required laparotomy to relieve obstruction. There were no treatment-related deaths. Seven of the 51 patients are alive and free of disease, 2 died from other causes, and 2 are alive with evidence of recurrent or progressive disease. Mean follow-up time for surviving patients is 78.5 months. Overall survival at 2, 5, and 10 years was 65, 27, and 10%, respectively. Residual disease after primary surgery, smaller preirradiation tumor residuum, and completion of radiotherapy were independently associated with improved overall survival. CONCLUSION: In this poor-prognosis group of patients, a combined approach of surgery, chemotherapy, and radiotherapy, while associated with acceptable toxicity, may not afford a prolongation of survival.

Abdomen↗
PubMed1999

Depression and the interpretation of ambiguity.

A number of studies have produced findings consistent with the possibility that depressives display a negative bias in interpretation. However, the results of such studies can equally well be explained by the operation of a depression-linked response bias, reflecting an elevated tendency for depressives to emit or endorse negatively-toned response options. The present experiment compares the patterns of interpretative processing displayed by subjects who differ in their BDI scores, using a priming methodology developed by anxiety researchers to eliminate the contaminating influence of emotional response bias. The pattern of priming effects obtained provides no evidence to support the existence of a negative interpretative bias in the more depressive individuals. Indeed, quite the reverse conclusion is sustained by the findings, which indicate that high BDI subjects showed an attenuated tendency to activate the more negative interpretations of the ambiguous textual stimuli. The conceptual and methodological implications of these findings are discussed, together with some specific suggestions for future research on this topic.

Adult↗
PubMed1999

Effects of female relative support in labor: a randomized controlled trial.

BACKGROUND: This study was a randomized controlled trial of primigravidas in Botswana to determine the effectiveness of the presence of a female relative as a labor companion on labor outcomes. METHODS: One hundred and nine primigravidas in uncomplicated spontaneous labor were randomly distributed into a control group who labored without family members present, and an experimental group who had a female relative with them during labor. RESULTS: Significantly more mothers in the experimental group had a spontaneous vaginal delivery (91% vs 71%), less intrapartum analgesia (53% vs 73%), less oxytocin (13% vs 30%), fewer amniotomies to augment labor (30% vs 54%), fewer vacuum extractions (4% vs 16%), and fewer cesarean sections (6% vs 13%) than in the control group. These differences were all significant at p < 0.05. Epidural analgesia was not used in the hospital at the time of the study. The only analgesics used were intramuscular pethidine or hyoscine N-butylbromide (Buscopan). CONCLUSIONS: The presence in labor of a female relative was shown to be associated with fewer interventions and a higher frequency of normal delivery compared with the outcomes of those without family member support. The presence of a female relative as a labor companion is a low-cost, preventative intervention that is consistent with the traditional cultural practices in Botswana. In the light of this and previous studies, all women giving birth in a hospital should be offered the choice of a female relative as a companion to give support during labor.

Adult↗
PubMed1999

Doctors' participation in randomized trials of adjuvant systemic therapy in breast cancer: how does it relate to their recommendations for standard therapy in breast cancer?

A cross-sectional survey of all medical and radiation oncologists in Australia was undertaken, plus surgeons listed as participants of the ANZ Breast Cancer Trials Group, to examine whether doctors' participation in randomized trials of adjuvant systemic therapy for breast cancer, is associated with their recommendations for adjuvant therapy in two clinical scenarios. Two-hundred and sixty-nine questionnaires were returned (response rate 71%). Fifty-six per cent of respondents, were participating in current adjuvant systemic therapy trials. Radiation oncologists were significantly more likely than surgeons or medical oncologists to recommend radiotherapy, while medical oncologists and surgeons were significantly more likely than radiation oncologists to recommend chemotherapy, in both clinical scenarios. In a multivariate analysis adjusting for the differences between specialist groups, respondents recommending chemotherapy were more likely to be high accruers to clinical trials (OR 3.6, 95% CI 0.93 to 13.9, P=0.08) in scenario 1, or participants of a breast cancer trials organization (OR 3.1, 95% CI 1.6 to 5.9, P=0.001) in scenario 2. Some of the variation in adjuvant systemic therapy recommendations is associated with participation in adjuvant systemic therapy trials. However, this study is unable to determine if trial participation influences opinions about adjuvant therapy, or opinions influence trial participation.

Journal Article↗
PubMed1999

Osteolymphoma (primary bone lymphoma): an Australian review of 70 cases. Australasian Radiation Oncology Lymphoma Group (AROLG).

BACKGROUND: To examine prognostic factors, treatment outcomes and design future studies for Osteolymphoma (OL)--also known as primary bone lymphoma. METHODS: Between 1979 and 1993, 70 patients with OL were treated in nine Australian centres. The effect of patient-, tumour-, and treatment-related factors on local control, distant disease-free survival and overall survival were assessed by multivariate analysis. RESULTS: Most patients (94%) received radiotherapy (RT) (median dose 40 Gy) and 56% received chemotherapy. Multifocal disease was present in 20% of patients. The five year rates of overall survival and local control were 59% and 82%. Although there was a trend towards better results with the addition of chemotherapy, on multivariate analysis, there were no factors identified which appeared to impact upon overall and disease-free survival. Among the distant recurrences, there was a high proportion in bone (33%). Six patients suffered pathological fractures after treatment. CONCLUSION: High rates of local control were achieved by RT, but the overall survival remains relatively poor, worse than nodal lymphoma. The natural history of the disease suggests that OL may be a distinct entity, different to nodal lymphomas, so the results of clinical trials in nodal lymphoma may not be relevant to OL. Prospective studies could define the outcome of combined modality therapy and set a benchmark for testing further proposals, as well as improving our knowledge of the clinical features of OL.

Adult↗
PubMed1999

Argument for the surgical staging of apparent early endometrial cancer.

Cancer of the uterine corpus, commonly referred to as cancer of the endometrium or cancer of the uterus, continues to be the most common pelvic genital malignancy affecting western women (1). In 1998 in the United States 36,100 women were diagnosed with this cancer, and there were 6,300 deaths from this condition in that year. Of concern is that despite a relatively stable incidence over the last decade, the annual number of deaths since 1987 from endometrial cancer has more than doubled (2). Many controversies exist in the management of apparent early endometrial cancer. These include: 1. The role of surgical staging which includes pelvic lymphadenectomy. 2. The role of the subspecialist gynaecological oncologist in primary surgical treatment. 3. Indications for vaginal and external beam radiotherapy. 4. Who is at risk for recurrence? 5. The role of laparoscopic approach to the management of this disease. Despite their importance, these and other issues have not been appropriately addressed by prospective randomized studies. Treatment strategies and algorithms have thus been based upon a combination of clinicopathological studies and uncontrolled reviews. The views expressed in this clinical opinion are those of the Sydney Gynaecologic Oncology Group and reflect our philosophy on the current management of this tumour, supported by recent and appropriate peer reviewed scientific literature.

Brachytherapy↗
PubMed1999

Modern radiotherapy. Does the GP have a role?

BACKGROUND: Radiotherapy has advanced dramatically in the last 20 years. OBJECTIVE: This article describes the basic biology of radiotherapy, which has led to models being produced that predict for outcome and side effects. Technical innovations allow for better tumour localisation and dose delivery. DISCUSSION: Radiotherapy has an important role in the multi-disciplinary care of the cancer patient and early involvement of a radiation oncologist may help optimise an individual patient's care.

Family Practice↗
PubMed1999

Investigating fatigue of less than 6 months' duration. Guidelines for family physicians.

OBJECTIVE: To develop an evidence-based systematic approach to assessment of adult patients who present to family physicians complaining of fatigue of less than 6 months' duration. The guidelines present investigative options, making explicit what should be considered in all cases and what should be considered only in specific situations. They aim to provide physicians with an approach that, to the extent possible, is based on evidence so that time and cost are minimized and detection and management of the cause of the fatigue are optimized. QUALITY OF EVIDENCE: MEDLINE was searched from 1966 to 1997 using the key words "family practice" and "fatigue." Articles about chronic fatigue syndrome were excluded. Articles with level 3 evidence were found, but no randomized trials, cohort studies, or case-control studies were found. Articles looking specifically at the epidemiology, demographics, investigations, and diagnoses of patients with fatigue were chosen. Articles based on studies at referral and specialty centres were given less weight than those based on studies in family physicians' offices. MAIN MESSAGE: Adherence to these guidelines will decrease the cost of investigating the symptom of fatigue and optimize diagnosis and management. This needs to be proved in practice, however, and with research that produces level 1 and 2 evidence. CONCLUSIONS: Adults presenting with fatigue of less than 6 months' duration should be assessed for psychosocial causes and should have a focused history and physical examination to determine whether further investigations should be done. The guidelines outline investigations to be considered. The elderly require special consideration. These guidelines have group validation, but they need to be tested by more physicians in various locations and types of practices.

Adult↗