Biomedical subjects

P Blake

Publications and source records attributed to P Blake.

At least 19 recordsLinked to original sources

PubMed2007

Recurrent endometrial cancer: patterns of recurrent disease and assessment of prognosis.

AIM: To evaluate patterns of disease and identify factors predicting outcome in patients presenting with recurrent endometrial adenocarcinoma following primary surgery. MATERIALS AND METHODS: A retrospective review was performed of the imaging and clinical data in 86 patients (median age 66 years, range 42-88 years) presenting with recurrent endometrial adenocarcinoma following primary surgery. RESULTS: Following primary surgery recurrent disease occurred within 2 years in 64% and within 3 years in 87%. Relapse was seen within lymph nodes in 41 (46%), the vagina in 36 (42%) the peritoneum in 24 (28%) and the lung in 21 (24%). Unusual sites of disease included spleen, pancreas, rectum, muscle and brain. Univariate survival analysis showed the factors significant for poor outcome were: multiple sites of disease, liver and splenic disease, haematogenous, peritoneal and nodal spread, poorly differentiated tumour, and early relapse. The presence of disease within the vagina, bladder or lung was not associated with poor prognosis. Multivariate analysis identified multiple sites of disease, liver and splenic metastases to be independent predictors of poor outcome. CONCLUSION: The most frequently observed sites of relapse are: lymph nodes, vagina, peritoneum and lung. Significant predictors of poor outcome in recurrent disease are multiple sites of disease and liver and splenic metastases.

Adenocarcinoma↗

PubMed2006

Movement of the cervix in after-loading brachytherapy: implications for designing external-beam radiotherapy boost fields.

AIMS: Women with invasive carcinoma of the cervix treated by chemo-radiotherapy and brachytherapy may also receive a pelvic sidewall boost using a midline shield (MLS). The purpose of this study was to assess the usefulness of implanted gold grains in detecting the movement of the cervix caused by the insertion of low-dose-rate brachytherapy applicators, and its implications in designing the MLS. MATERIALS AND METHODS: The medical records of 42 women with various stages of cervical carcinoma, who were treated by radical chemo-radiotherapy, were reviewed. All of these women underwent examination under anaesthesia (EUA) and a gold-grain insertion to demarcate the vaginal tumour extent, in the antero-posterior and lateral planes, before starting external-beam radiotherapy. The isocentric orthogonal films (simulator films) of external radiotherapy and brachytherapy were compared to assess the change in position of the gold grains and the consequences for the design of the MLS for parametrial and pelvic sidewall boosts. RESULTS: A significant shift in the position of the gold grains was noted in both the x (lateral) and the y (cranial/caudal) axes. The median shift of the midline, right and left lateral gold grains was 4.5, 5 and 7 mm in the x axis, whereas it was 10, 8 and 9.5 mm in the y axis, respectively. The median shift in the x and y axes was 5.5 and 9 mm, ranging from 1 to 40 mm and 1 to 45 mm, respectively. The gold grains were shifted cranially in 34 (80%) and laterally in 29 (69%) women. Thirty-two women (76.2%) received parametrial boost radiotherapy, of which 25 (59.5%) women had a customised, pear-shaped shield, and the remaining seven (16.7%) had a straight-sided, rectangular MLS. Four women (9.5%) relapsed locally, and three of them had been treated using a customised shield. In two of these four women, there was an absolute under-dosage of the central pelvis at the tip of the intra-uterine tube by 50% of the parametrial boost dose (5.4 Gy/3 fractions/3 days). CONCLUSIONS: Insertion of the gold grains during pre-treatment EUA is a useful technique in detecting the movement of the cervix. A significant shift in the position of the gold grains was noted in both the x (lateral) and the y (cranial/caudal) axes. These shifts in the cervix can result in under-dosage of the central pelvis when delivering parametrial boosts with the MLS in place on the basis of the brachytherapy check films. When designing the individualised MLS, the resulting under-dosage could be avoided by taking account of the shift in the gold grain markers and allow the delivery of a more homogenous dose to the pelvis.

Adult↗

PubMed2005

Evaluation of a software package for automated quality assessment of contrast detail images--comparison with subjective visual assessment.

Contrast detail analysis is commonly used to assess image quality (IQ) associated with diagnostic imaging systems. Applications include routine assessment of equipment performance and optimization studies. Most frequently, the evaluation of contrast detail images involves human observers visually detecting the threshold contrast detail combinations in the image. However, the subjective nature of human perception and the variations in the decision threshold pose limits to the minimum image quality variations detectable with reliability. Objective methods of assessment of image quality such as automated scoring have the potential to overcome the above limitations. A software package (CDRAD analyser) developed for automated scoring of images produced with the CDRAD test object was evaluated. Its performance to assess absolute and relative IQ was compared with that of an average observer. Results show that the software does not mimic the absolute performance of the average observer. The software proved more sensitive and was able to detect smaller low-contrast variations. The observer's performance was superior to the software's in the detection of smaller details. Both scoring methods showed frequent agreement in the detection of image quality variations resulting from changes in kVp and KERMA(detector), which indicates the potential to use the software CDRAD analyser for assessment of relative IQ.

Algorithms↗

PubMed2005

Is supplementation with elemental diet feasible in patients undergoing pelvic radiotherapy?

BACKGROUND: Acute gastrointestinal upset occurs in approximately 80% of patients undergoing radiotherapy for pelvic cancers. Underlying changes relate to denudation of the mucosal layer which renders the small intestine vulnerable to additional damage from proteolytic enzymes and bile acids. Severe acute bowel symptoms may predispose to progressive fibrotic and ischaemic changes. Elemental diet given during treatment may reduce acute and chronic bowel symptoms induced by pelvic radiotherapy. METHODS: This study aimed to assess compliance with elemental diet during pelvic radiotherapy. Patients with gynaecological, urological or rectal malignancy undergoing radical or adjuvant pelvic radiotherapy were randomised to one of five groups. Each group was assigned a target quantity of three different elemental sip feeds (Group 1, 20%, Group 2, 50%, Group 3, 75% of calorie requirements taken as E028 extra liquid; Group 4, 50% of calorie requirements taken as E028 extra powder; Group 5, 50% of calorie requirements taken as Emsogen powder). Compliance was assessed using a diary card and weekly assessment. Statistical analyses were conducted on an intention to treat basis. RESULTS: Fifty patients (44 female, six male) mean age 58 yr (95% CI 55-61), were recruited to the study (24 endometrial, 17 cervical, 7 rectal, 1 vulval and 1 bladder carcinoma). Mean weight at baseline was 74.5 kg (95% CI 69-80) and this did not change during treatment. Full compliance was achieved in three patients, all from Group 1. By week 5, only 46% of patients were consuming elemental diet. Post hoc analysis of variance with repeated measures indicated that there were no significant differences in volume of elemental diet consumed between groups (P = 0.937). There was a significant inverse linear relationship between intake of elemental diet and time (P < 0.001). CONCLUSIONS: Different formulations of elemental diet do not influence compliance. Patients are unlikely to be able to consume more than one-third of their calorie requirements in the form of an elemental sip feed. Further investigation is warranted to determine if intervention with this volume of elemental diet is beneficial.

Analysis of Variance↗

PubMed2005

A modified Inflammatory Bowel Disease questionnaire and the Vaizey Incontinence questionnaire are simple ways to identify patients with significant gastrointestinal symptoms after pelvic radiotherapy.

After radiotherapy for pelvic cancer, chronic gastrointestinal problems may affect quality of life (QOL) in 6-78% of patients. This variation may be due to true differences in outcome in different diseases, and may also represent the inadequacy of the scales used to measure radiotherapy-induced gastrointestinal side effects. The aim of this study was to assess whether outcome measures used for nonmalignant gastrointestinal disease are useful to detect gastrointestinal morbidity after radiotherapy. Results obtained from a Vaizey Incontinence questionnaire and a modified Inflammatory Bowel Disease questionnaire (IBDQ)--both patient completed--were compared to those from a staff administered Late Effects on Normal Tissue (LENT)--Subjective, Objective, Management and Analytic (SOMA) questionnaire in patients who had completed radiotherapy for a pelvic tumour at least 3 months previously. In all, 142 consecutive patients were recruited, 72 male and 70 female, median age 66 years (range 26-90 years), a median of 27 (range 3-258) months after radiotherapy. In total, 62 had been treated for a gynaecological, 58, a urological and 22, a gastrointestinal tract tumour. Of these, 21 had undergone previous gastrointestinal surgery and seven suffered chronic gastrointestinal disorders preceding their diagnosis of cancer. The Vaizey questionnaire suggested that 27% patients were incontinent for solid stools, 35% for liquid stools and 37% could not defer defaecation for 15 min. The IBDQ suggested that 89% had developed a chronic change in bowel habit and this change significantly affected 49% patients: 44% had more frequent or looser bowel movements, 30% were troubled by abdominal pain, 30% were troubled by bloating, 28% complained of tenesmus, 27% were troubled by their accidental soiling and 20% had rectal bleeding. At least 34% suffered emotional distress and 22% impairment of social function because of their bowels. The small intestine/colon SOMA median score was 0.1538 (range 0-1) and the rectal SOMA median score was 0.1428 (range 0-1). Pearson's correlations for the IBDQ score and small intestine/colon SOMA score was -0.630 (P<0.001), IBDQ and rectum SOMA -0.616 (P<0.001), IBDQ and Vaizey scores -0.599 (P<0.001), Vaizey and small intestine/colon SOMA 0.452 (P<0.001) and Vaizey and rectum SOMA 0.760 (P<0.001). After radiotherapy for a tumour in the pelvis, half of all patients develop gastrointestinal morbidity, which affects their QOL. A modified IBDQ and Vaizey questionnaire are reliable in assessing new gastrointestinal symptoms as well as overall QOL and are much easier to use than LENT SOMA.

Adult↗

PubMed2005

The significance of rectal bleeding after pelvic radiotherapy.

BACKGROUND: Rectal bleeding after pelvic radiotherapy is often attributed to radiation proctitis and patients do not routinely undergo flexible endoscopy. AIMS: To assess the significance of bleeding after radiotherapy. METHODS: We maintained a prospective register of all such patients referred to our endoscopy unit. RESULTS: One hundred and thirty-nine men (median age 70 years; range 31-82), and 32 women (median age 61 years; range 30-81) were referred with rectal bleeding (median 2 years; range 0-21) after pelvic radiotherapy. Primary tumour sites were urological (n = 139), gastrointestinal (n = 7) and gynaecological (n = 25). Ninety patients had bleeding alone; 81 had other symptoms. One hundred and forty-one had typical radiation proctitis; in 65 this was the sole diagnosis; eight had cancer, nine had high-risk adenomas, and six had three or more small adenomas. Ninety-five other diagnoses were made. Eleven (73%) patients with advanced polyps or cancer required only flexible sigmoidoscopy to make the diagnosis, while four (27%) diagnoses were made only after colonoscopy; 47% of these patients had no other symptoms apart from rectal bleeding. CONCLUSIONS: After pelvic radiotherapy, clinical symptoms are not reliable in differentiating between radiation proctitis alone or more significant pathology. It is mandatory that all patients with new onset rectal bleeding are investigated with, at least, flexible sigmoidoscopy.

Adult↗

PubMed2005

Do serum levels of eosinophil granule-derived protein change in patients undergoing pelvic radiotherapy?

AIMS: Eosinophils have an important role in the pathogenesis of inflammatory bowel disease, with faecal levels of the eosinophil granule proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX) reflecting disease activity. Eosinophil crypt abscesses are a characteristic histological finding in acute gastrointestinal radiation-induced mucosal damage. This pilot study aimed to investigate changes in serum levels of ECP/EPX during pelvic radiotherapy. MATERIALS AND METHODS: Patients with no history of inflammatory bowel disease, starting a 5-week course of pelvic radiotherapy, had serum ECP/EPX levels measured before radiotherapy and during the fourth week of treatment. Bowel toxicity was graded at week 4 using the Common Toxicity Criteria Scale. RESULTS: Fifteen patients who were to undergo adjuvant radiotherapy for gynaecological cancer were recruited. The mean serum levels of ECP and EPX before treatment were 17.3 microg/l (range 2.0-49.3 microg/l) and 37.3 microg/l (range 12.0-94.0 microg/l), respectively. The mean serum levels during week 4 of radiotherapy for ECP and EPX were 43.0 microg/l (range 2.4-164.0 microg/l) and 38.7 microg/l (range 9.0-79.0 microg/l), respectively. Serum ECP levels increased at week 4 compared with levels before radiotherapy (P = 0.02). Acute bowel toxicity was seen in 12 patients (80%) at week 4: Grade 1 in 25% patients and Grade 2 in 75%. In this small study, no correlation was seen between acute bowel toxicity at week 4 and serum ECP or EPX levels. CONCLUSIONS: Serum ECP levels increase in response to pelvic irradiation. This may reflect the known involvement of eosinophils in the acute response to radiotherapy. Further study is required to determine when levels start to rise and their relationship to the degree of acute bowel toxicity.

Aged↗

PubMed2004

Treatment of uterine sarcoma at the Royal Marsden Hospital from 1974 to 1998.

AIMS: Uterine sarcomas are rare tumours with histopathological diversity characterised by rapid clinical progression and poor prognosis. Optimal management consists of complete surgical removal, but is not clear whether adjuvant radiotherapy improves the prognosis. The aim of this retrospective study was to investigate the clinical and histopathological characteristics together with treatment and outcome of patients with uterine sarcomas. MATERIALS AND METHODS: Records of 100 patients treated at the Royal Marsden Hospital between 1974-1998 were reviewed: 47 leiomyosarcoma (LMS), 30 mixed mullerian tumours (MMT), 19 endometrial stromal sarcoma (ESS), one haemangiopericytoma, one rhabdomyosarcoma and two unspecified sarcoma. There were 50, 11, 21 and 18 patients with stage I, II, III and IV carcinoma, respectively. Thirty-four patients had high-grade disease. Fifty-three patients received adjuvant radiotherapy. The median age was 55 years (range: 18-83 years). The median follow-up was 54 months (range: 3 months to 27 years). RESULTS: The overall 3, 5 and 10-year survival rates were 39%, 30% and 20%, respectively. Survival was significantly related to stage (P = 0.002), grade (P = 0.003) and histological type (P = 0.04), but not to use of postoperative irradiation. At 3 years, the survival rate was 42% for LMS, 22% for MMT and 63% for ESS. Local recurrence rate, however, was significantly improved after adjuvant radiotherapy with dose higher than 50 Gy (P = 0.001). CONCLUSIONS: Prognosis is dependent on histopathological sub-type, grade and tumour stage. Adjuvant radiotherapy decreases local recurrence rate, but without significant impact on survival.

Adolescent↗

PubMed2003

Uterine sarcoma: twenty-seven years of experience.

PURPOSE: A correlation of treatment for uterine sarcoma with outcome, prognostic importance of pathology, and clinical parameters. PATIENTS AND METHODS: One hundred forty-one patients (median age: 56 years, range: 19-85 years) with a histologically verified uterine sarcoma were identified from a database compiled at the Royal Marsden Hospital and the University of Florence between 1974 and 2001. Seventy-two patients had leiomyosarcoma, 42 had mixed müllerian tumors, 22 had endometrial stromal sarcoma, 1 hemangiopericytoma, 1 rhabdomyosarcoma, and 3 patients had unspecified sarcoma. According to FIGO classification, Stage I, II, III, and IV tumors were identified in 71, 13, 31, and 26 patients, respectively. RESULTS: At the time of analysis, 73.7% of patients were dead, and 26.3% were alive with a median survival of 2 years from initial diagnosis. Univariate analysis for cause-specific survival demonstrated statistical significance for histology (p = 0.02), grade (p = 0.003), stage (p = 0.007), and age (p = 0.02). Multivariate analysis demonstrated significant prognostic values for stage (p = 0.02) and histology (p = 0.05) only. Postoperative radiotherapy with a total dose higher than 50 Gy seems to be significant (p = 0.001) in reducing local recurrence. CONCLUSIONS: Our data favor treatment for Stages I, II, and III of uterine sarcoma with radical surgery plus radical dose irradiation comprising both external beam radiotherapy and brachytherapy.

Adult↗

PubMed2003

How patients manage gastrointestinal symptoms after pelvic radiotherapy.

BACKGROUND: Approximately 13,000 patients undergo pelvic radiotherapy annually in the UK. It is not clear how frequently patients develop a permanent change in bowel habit after pelvic radiotherapy that affects their quality of life because the measures of gastrointestinal toxicity used in trials in the past have generally been inadequate. It has been suggested that patients who are symptomatic are only rarely referred to a gastroenterologist and it is not known how patients manage their symptoms. METHODS: Patients who had completed radiotherapy for pelvic cancer at least 1 year previously were invited to answer 30 structured questions in a face-to-face interview to determine the frequency of gastrointestinal symptoms and what orthodox, dietary and complementary therapies they used to deal with them. They were also asked to score the effectiveness of the measures they had taken. RESULTS: One hundred and seven patients were recruited [35 males; median age, 65 years (range, 35-80 years); 72 females; median age, 67.5 years (range, 31-87 years)]. Eight had been treated for a gastrointestinal primary tumour, 34 for a urological tumour and 65 for gynaecological tumours. Eighty-seven patients (81%) described new-onset gastrointestinal problems starting after radiotherapy. These symptoms affected the quality of life in 56 patients (52%). Significant effects on the quality of life were caused by diarrhoea or constipation (n = 53), faecal leakage (n = 19), abdominal, rectal or perineal pain (n = 14) and rectal bleeding (n = 6). Fifty-nine patients had seen a doctor for their symptoms (86% found this helpful), 12 had seen a dietician or nurse (50% found this helpful) and 14 had seen alternative practitioners (88% found this helpful). Dietary manipulation generally did not improve symptoms, except in a small group of patients (14/15) who avoided raw vegetables to great benefit. CONCLUSIONS: At least 1 year after pelvic radiotherapy, gastrointestinal symptoms which have an adverse effect on the quality of life may be more common than generally reported. Patients found that advice from doctors and alternative practitioners was equally valuable. Dietary manipulation was generally unhelpful for gastrointestinal symptoms after pelvic radiotherapy, although the role of eliminating raw vegetables may benefit from further evaluation.

Adult↗

PubMed2003

Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group.

BACKGROUND: Combination chemotherapy yields better response rates which do not always lead to a survival advantage. The aim of this study was to investigate whether the reported differences in the efficacy and toxicity of monotherapy with doxorubicin (DOX) versus combination therapy with cisplatin (CDDP) in endometrial adenocarcinoma lead to significant advantage in favour of the combination. PATIENTS AND METHODS: Eligible patients had histologically-proven advanced and/or recurrent endometrial adenocarcinoma and were chemo-naïve. Treatment consisted of either DOX 60 mg/m(2) alone or CDDP 50 mg/m2 added to DOX 60 mg/m2, every 4 weeks. RESULTS: A total of 177 patients were entered and median follow-up is 7.1 years. The combination DOX-CDDP was more toxic than DOX alone. Haematological toxicity consisted mainly of white blood cell toxicity grade 3 and 4 (55% versus 30%). Non-haematological toxicity consisted mainly of grade 3 and 4 alopecia (72% versus 65%) and nausea/vomiting (36 % versus 12%). The combination DOX-CDDP provided a significantly higher response rate than single agent DOX (P <0.001). Thirty-nine patients (43%) responded on DOX-CDDP [13 complete responses (CRs) and 26 partial responses (PRs)], versus 15 patients (17%) on DOX alone (8 CR and 7 PR). The median overall survival (OS) was 9 months in the DOX-CDDP arm versus 7 months in the DOX alone arm (Wilcoxon P = 0.0654). Regression analysis showed that WHO performance status was statistically significant as a prognostic factor for survival, and stratifying for this factor, treatment effect reaches significance (hazard ratio = 1.46, 95% confidence interval 1.05-2.03, P = 0.024). CONCLUSIONS: In comparison to single agent DOX, the combination of DOX-CDDP results in higher but acceptable toxicity. The response rate produced is significantly higher, and a modest survival benefit is achieved with this combination regimen, especially in patients with a good performance status.

Adenocarcinoma↗

PubMed2002

A population-based estimate of the burden of diarrhoeal illness in the United States: FoodNet, 1996-7.

This study was performed to better understand and more precisely quantify the amount and burden of illness caused by acute diarrhoea in the United States today. A telephone-based population survey was conducted between 1 July, 1996, and 31 June, 1997, in sites of the Foodborne Diseases Active Surveillance Network (FoodNet). The overall prevalence of acute diarrhoea in the 4 weeks before interview was 11%, giving a rate of 1.4 episodes of diarrhoea per person per year. The rate of diarrhoeal illness defined as a diarrhoeal episode lasting longer than 1 day or which resulted in significant impairment of daily activities was 0.7 per person per year. It can be concluded that acute diarrhoea is common and represents a significant burden of illness in the United States. Our data on self-reported diarrhoea, when generalized to the entire nation, suggests 375 million episodes of acute diarrhoea each year in the United States. Many of these episodes are mild. However, our data also indicate that there are approximately 200 million episodes of diarrhoeal illness each year in the United States.

Acute Disease↗

PubMed2002

Canadian survey of clinical status at dialysis initiation 1998-1999: a multicenter prospective survey.

AIMS: The current growth in end-stage kidney disease populations has led to increased efforts to understand the impact of status at dialysis initiation on long-term outcomes. Our main objective was to improve the understanding of current Canadian nephrology practice between October 1998 and December 1999. METHODS: Fifteen nephrology centers in 7 provinces participated in a prospective data collection survey. The main outcome of interest was the clinical status at dialysis initiation determined by: residual kidney function, preparedness for chronic dialysis as measured by presence or absence of permanent peritoneal or hemodialysis access, hemoglobin and serum albumin. Uremic symptoms at dialysis initiation were also recorded, however, in some cases these symptom data were obtained retrospectively. RESULTS: Data on 251 patients during 1-month periods were collected. Patients commenced dialysis at mean calculated creatinine clearance levels of approximately 10 ml/min, with an average of 3 symptoms. 35% of patients starting dialysis had been known to nephrologists for less than 3 months. These patients are more likely to commence without permanent access and with lower hemoglobin and albumin levels. Even of those known to nephrologists, only 66% had permanent access in place. CONCLUSIONS: Patients commencing dialysis in Canada appear to be doing so in relative concordance with published guidelines with respect to timing of initiation. Despite an increased awareness of kidney disease, a substantial number of patients continues to commence dialysis without previous care by a nephrologist. Of those who are seen by nephrologists, clinical and laboratory parameters are suboptimal according to current guidelines. This survey serves as an important baseline for future comparisons after the implementation of educational strategies for referring physicians and nephrologists.

Adult↗

PubMed2001

Chlorine inactivation of Escherichia coli O157:H7 in water.

Six human isolates of Escherichia coli O157:H7 and E. coli (ATCC 11229) were used to determine the concentrations of free chlorine and exposure times required for inactivation. Free chlorine concentrations of 0.25, 0.5, 1.0, and 2.0 ppm at 23 degrees C were evaluated, with sampling times at 0, 0.5, 1.0, and 2.0 min. Results revealed that five of six E. coli O157:H7 isolates and the E. coli control strain were highly susceptible to chlorine, with >7 log10 CFU/ml reduction of each of these strains by 0.25 ppm free chlorine within 1 min. However, comparatively, one of the seven strains was unusually tolerant to chlorine at 23 degrees C for 1 min, with a 4-, 5.5-, 5.8-, and >5.8-log CFU/ml reduction at free chlorine concentrations (ppm) of 0.25, 0.5, 1.0, and 2.0. respectively. Based on these studies most isolates of E. coli O157:H7 have no unusual tolerance to chlorine; however, one strain was exceptional in being recovered after 1-min of exposure of 10(7) CFU/ml to 2.0 ppm of free chlorine. This isolate may be a useful reference strain for future studies on chlorine tolerance of E. coli O157:H7.

Chlorine↗

PubMed2001

Pharmaceutical industry overview: optimal drug therapy.

Today's revolutionary genomics research is the key to the search for tomorrow's new drugs. Over the next 10 to 20 years, there could be 15 times the number of therapeutic agents that there are today. With these scientific advances, optimal drug therapy becomes an even more significant component of health care. Canada's Research-Based Pharmaceutical Companies have proposed a therapeutic management system designed to make the optimum use of health care while controlling costs. The proposal is based on the disease management approach, applied first to diseases that are the most widespread in the population and that represent the highest costs for the health care system. The concept involves comparing the best available practices with the care provided and making the necessary adjustments to improve patients' health in line with the most cost effective approach. Preliminary results from similar programs underway in Canada, such as those in the field of asthma treatment, suggest that they can lead to improvements in the quality of care and represent a step forward in comparison with measures focusing only on cutting costs. The future will bring new challenges in achieving optimal drug therapy as genomics leads to tailor-made medications, necessitating changes in drug plan policies and reimbursement. With personalized treatment regimens and an increased understanding of how to prevent and treat diseases, optimal drug therapy can be taken to a new level. Quality of life can be further improved, more lives can be saved and the health care system can be saved more money while providing the best possible treatments.

Canada↗

PubMed2000

Butyltins in shellfish, finfish, water and sediment from the Coos Bay estuary (Oregon, USA).

Butyltin was measured in tissue, water and sediment samples collected throughout Coos Bay estuary between 1986 and 1997. Butyltin-induced shell deformation in commercial oysters prompted this assessment. Butyltins are released from tributyltin oxide (TBTO)-containing boat paint. Clams from three sites contained tributyltin (TBT) levels ranging from 168 to 457 microg/kg in 1992-1994. Consequently, Oregon Health Division (OHD) issued a shellfish consumption advisory in 1995; it was rescinded in 1997 after US Environmental Protection Agency (EPA) revised the TBTO oral reference dose (RfD). The revised RfD changed the tissue screening level from 112 to 1120 microg TBT/kg. Fifty percent of sediment samples collected during 1991-1997 and analyzed for total butyltins (TotBT) exceeded the Puget Sound Dredge Disposal Analysis Screening Level (PSDDA SL) of 73 microg TBT/kg dw. TotBT at three shipyards selected for site assessment by EPA ranged from 24 to 68,613 microg/kg dw. Sediment and tissue butyltins have been decreasing in all but one area of the estuary.

Animals↗

PubMed2000

Combining platinum, paclitaxel and anthracycline in patients with advanced gynaecological malignancy.

Two meta-analyses have suggested that the addition of an anthracycline to platinum-based chemotherapy may improve survival in advanced ovarian cancer, and two randomised trials have demonstrated superiority of paclitaxel over cyclophosphamide in platinum combinations. A combination of platinum, anthracycline and paclitaxel would, therefore, be a reasonable experimental arm of any future randomised trial in patients with epithelial ovarian carcinoma (EOC). Patients who required chemotherapy for EOC but were ineligible for standard trials or had other gynaecological tumours that required similar platinum-based chemotherapy were considered for this pilot. The platinum/anthracycline/paclitaxel regimen (G-CAT) was given 3-weekly and consisted of doxorubicin 50 mg/m(2) or epirubicin 60 mg/m(2) intravenously (i.v.) bolus, paclitaxel 175 mg/m(2) (i.v.) over 3 h and either cisplatin 75 mg/m(2) (i.v.) or carboplatin AUC 6, with granulocyte colony-stimulating factor (G-CSF) at the neutrophil nadir. Different combinations were used in order to determine the least toxic regimen. Toxicity and response were assessed according to CTC and WHO criteria, respectively. 26 patients entered the study, 13 with EOC and 13 with other gynaecological cancers (peritoneal, fallopian tube, mixed Mullerian). Median age was 49 years (range: 27-67). 8 patients received carboplatin/doxorubicin/paclitaxel, 8 cisplatin/doxorubicin/paclitaxel and 10 carboplatin/epirubicin/paclitaxel. A total of 135 cycles of chemotherapy were delivered, with a median of 6 cycles per patient (range: 2-6). 54 (40%) cycles required G-CSF support and 17 (65%) patients required at least one dose reduction. All patients experienced grade 4 neutropenia and 13 (50%) patients developed grade 3-4 thrombocytopenia (12 of whom had received carboplatin). There were 4 (15%) patients with grade 3/4 infections but no septic deaths. Non-haematological toxicities were manageable, lethargy occurred in 75% of cisplatin-treated patients. Grade 1/2 cardiotoxicity, as assessed pre- and post-treatment by left ventricular ejection fraction, was observed in 6/13 (46%) patients who had received doxorubicin and 2/7 (29%) epirubicin-treated patients. No clinically detectable cardiac toxicity was encountered. The response rate in 25 evaluable patients was 76% (12 CR, 7 PR). Dose intensity was highest in the carboplatin/epirubicin/paclitaxel combination. G-CAT shows high activity and can be administered safely, but only very fit patients are suitable for this regimen as it is associated with considerable toxicity. Carboplatin/epirubicin/paclitaxel was the best tolerated regimen overall.

Adult↗

PubMed2000

A patient with 17 primary tumours and a germ line mutation in TP53: tumour induction by adjuvant therapy?

We report the case history of a woman with a germ line mutation in the TP53 gene who developed 17 separate primary tumours. The incidence of new tumours rose steeply after adjuvant tamoxifen treatment for breast cancer and adjuvant vaginal vault radiotherapy for endometrial cancer. This increase could be due to cumulative genetic damage from environmental agents and the fact that the patient lived to the relatively late age of 60 years, or to a high inherent deleterious somatic mutation rate, which could represent the inability of cells from patients with TP53 mutations to repair therapy-induced genetic damage.

Antineoplastic Agents, Hormonal↗