Search PubMed⌕ Search

Biomedical subjects

C MacLeod

Publications and source records attributed to C MacLeod.

At least 19 recordsLinked to original sources
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

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↗
PubMed1998

High-dose-rate brachytherapy alone post-hysterectomy for endometrial cancer.

PURPOSE: To evaluate the outcome of post-hysterectomy adjuvant vaginal high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: A retrospective analysis was performed on a series of 143 patients with endometrial cancer treated with HDR brachytherapy alone post-hysterectomy from 1985 to June 1993. Of these patients, 141 received 34 Gy in four fractions prescribed to the vaginal mucosa in a 2-week period. The median follow-up was 6.9 years. Patients were analyzed for treatment parameters, survival, local recurrence, distant relapse, and toxicity. RESULTS: Five-year relapse free survival and overall survival was 100% and 88% for Stage 1A, 98% and 94% for Stage IB, 100% and 86% for Stage IC, and 92% and 92% for Stage IIA. The overall vaginal recurrence rate was 1.4%. The overall late-toxicity rate was low, and no RTOG grade 3, 4, or 5 complications were recorded. CONCLUSION: These results are similar to reported international series that have used either low-dose-rate or HDR brachytherapy. The biological effective dose was low for both acute and late responding tissues compared with some of the HDR brachytherapy series, and supports using this lower dose and possibly decreasing late side-effects with no apparent increased risk of vaginal recurrence.

Adult↗
PubMed1998

Two case reports: carcinoma of the cervix and carcinoma of the endometrium treated with radiotherapy after previous irradiation for benign uterine bleeding.

In the 1940s, 1950s and 1960s, low doses of radiotherapy were used to treat benign uterine bleeding. The cases of two women who received this form of therapy and later developed gynaecological malignancies and had high-dose pelvic radiotherapy are presented. A 76-year-old woman with an International Federation of Gynecology and Obstetrics (FIGO) stage-IIB squamous cell carcinoma of the cervix received external beam radiotherapy and intra-uterine brachytherapy and a 77-year-old women with a FIGO stage-IB endometrial adenocarcinoma received adjuvant postoperative pelvic radiotherapy. Both women had a significant past history of low-dose-rate intra-uterine irradiation for dysfunctional uterine bleeding. Therefore the theoretical question of carcinogenesis was raised, and also the practical questions of what dose had previously been given and what further dose could be safely given with regard to normal tissue tolerance.

Adenocarcinoma↗
PubMed1997

High-dose-rate brachytherapy in the management of high-grade intraepithelial neoplasia of the vagina.

The majority of women with high-grade intraepithelial neoplasia (VAIN 3) are over 60 years of age and have a history of premalignant or malignant disease of the cervix. Although the natural history of VAIN is not well defined, high-grade lesions are premalignant. Ablative treatment with laser or 5-fluorouracil cream is commonly unsatisfactory. Several series have reported a low rate of recurrence and complications if VAIN 3 is treated with low-dose-rate brachytherapy. This retrospective review reports the outcome of 14 patients treated with high-dose-rate brachytherapy, with a dose of 34 to 45 Gy in 4.5- to 8.5-Gy fractions. Treatment was well tolerated with no severe early or late toxicity observed. At a median follow-up of 46 months 1 patient progressed to invasive carcinoma of the vagina; in another patient VAIN 3 persisted.

Adult↗