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Biomedical subjects

Michael Sharpe

Publications and source records attributed to Michael Sharpe.

18 recordsLinked to original sources

Ongoing clinical experience utilizing 3D conformal external beam radiotherapy to deliver partial-breast irradiation in patients with early-stage breast cancer treated with breast-conserving therapy.

PURPOSE: We present our ongoing clinical experience utilizing 3D conformal radiation therapy (3D-CRT) to deliver partial-breast irradiation (PBI) in patients with early-stage breast cancer treated with breast-conserving therapy. MATERIALS AND METHODS: Thirty-one patients referred for postoperative radiation therapy after lumpectomy were treated with PBI using our previously reported 3D-CRT technique. Ninety-four percent of patients had surgical clips outlining the lumpectomy cavity (mean: 6 clips). The clinical target volume (CTV) consisted of the lumpectomy cavity plus a 10-mm margin in 9 patients and 15-mm margin in 22 (median: 15 mm). The planning target volume consisted of the CTV plus a 10-mm margin for breathing motion and treatment setup uncertainties. The prescribed dose (PD) was 34 or 38.5 Gy (6 patients and 25 patients, respectively) in 10 fractions b.i.d. separated by 6 h and delivered in 5 consecutive days. Patients were treated in the supine position with 3-5 beams (mean: 4) designed to irradiate the CTV with <10% inhomogeneity and a comparable or lower dose to the heart, lung, and contralateral breast compared with standard whole-breast tangents. The median follow-up duration is 10 months (range: 1-30 months). Four patients have been followed >2 years, 6 >1.5 years, and 5 >1 year. The remaining 16 patients have been followed <12 months. RESULTS: No skin changes greater than Grade 1 erythema were noted during treatment. At the initial 4-8-week follow-up visit, 19 patients (61%) experienced Grade 1 toxicity and 3 patients (10%) Grade 2 toxicity. No Grade 3 toxicities were observed. The remaining 9 patients (29%) had no observable radiation effects. Cosmetic results were rated as good/excellent in all evaluable patients at 6 months (n = 3), 12 months (n = 5), 18 months (n = 6), and in the 4 evaluable patients at >2 years after treatment. The mean coverage of the CTV by the 100% isodose line (IDL) was 98% (range: 54-100%, median: 100%) and by the 95% IDL, 100% (range: 99-100%). The mean coverage of the planning target volume by the 95% IDL was 100% (range: 97-100%). The mean percentage of the breast receiving 100% of the PD was 23% (range: 14-39%). The mean percentage of the breast receiving 50% of the PD was 47% (range: 34-60%). CONCLUSIONS: Utilizing 3D-CRT to deliver PBI is technically feasible, and acute toxicity to date has been minimal. Additional follow-up will be needed to assess the long-term effects of these larger fraction sizes on normal-tissue sequelae and the impact of this fractionation schedule on treatment efficacy.

Aged↗

Techniques to modulate radiotherapy toxicity and outcome in soft tissue sarcoma.

Radiotherapy (RT) targeting of soft tissue sarcoma presents considerable opportunity and challenges in realizing the dual goals of tissue and function preservation and maintaining high local control. Traditional RT target volumes used for soft tissue sarcoma have largely been constrained by available technology and are not ideal in some situations. The advent of very precise treatment planning and delivery systems, including three-dimensional conformal radiotherapy and intensity-modulated radiotherapy, means it is possible to select target volumes that more closely approach the optimum. Consequently, these new approaches provide great opportunity for treatment enhancement in the future. It can be expected that newer techniques for RT planning and delivery will challenge the existing dogma concerning target delineation for optimal radiotherapy outcome. It can be foreseen that the precise knowledge of appropriate targets will continue to evolve for different clinical scenarios and likely be greatly influenced by enhanced imaging capability. Advancement of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy over the next decade must rely on the consistent reporting and sharing of results concerning outcome of normal tissue from volumetric treatment planning.

Clinical Trials as Topic↗

Diagnosing major depression in medical outpatients: acceptability of telephone interviews.

OBJECTIVE: To assess the acceptability to patients of a diagnostic interview for depression (Structured Clinical Interview for DSM-IV; SCID) conducted over the telephone to their homes. METHOD: Postal questionnaire survey of patients who had attended an oncology outpatient clinic where they had scored high on a screening questionnaire and had subsequently undergone an SCID interview over the telephone. RESULTS: Of the 224 patients telephoned, five refused the diagnostic interview. Of the 219 who were interviewed, 184 satisfactorily completed and returned the postal questionnaire (84% response rate). Only 17% reported the interview to be distressing. Ninety-four percent of all questionnaire respondents and 84% (n=31) of those who reported the interview to have been distressing endorsed the item "Had I known in advance what answering the questions would have been like for me, I would still have agreed to take part". Perceiving the interview as distressing was associated with having major depression (P<.001). Forty-seven percent said that, given the choice, they would have preferred a face-to-face interview. CONCLUSION: Telephone-administered diagnostic interviews are acceptable to most cancer patients and may even be preferred to face-to-face interviews at the hospital. This finding, together with the existing evidence of its validity, should encourage the use of telephone diagnostic interviews for depression, particularly when face-to-face interviews are impracticable, in both research studies and clinical practice. Indeed, a substantial proportion of patients may actually prefer them.

Depressive Disorder↗

What should we call pseudoseizures? The patient's perspective.

BACKGROUND: There are numerous terms to describe seizure-like episodes not explained by disease-for example pseudoseizures, psychogenic seizures and non-epileptic attack disorder. Debates about which is best to use tend to centre around theoretical arguments and not scientific evaluation. In this study we examine the meanings of these labels for patients, which have the least potential to offend, and consequently to provide a more positive basis for further management. METHODS AND RESULTS: We interviewed 102 consecutive general neurology outpatients who were asked to consider a scenario that they were being given a diagnosis by a doctor after experiencing a blackout with normal tests. We investigated 10 different diagnoses for blackouts with six different connotations. Three of these connotations--'putting it on', 'mad' and 'imagining symptoms'--were used to derive an overall 'offence score'. Using this score some labels were highly offensive, e.g. 'symptoms all in the mind' (89%) and 'hysterical seizures' (48%). There were no significant differences between the labels 'pseudoseizures', 'psychogenic seizures' and 'non-epileptic attack disorder'. 'Stress-related seizures' and 'functional seizures' were significantly less offensive than these three diagnoses and were equivalent to 'tonic-clonic' and 'grand mal'. CONCLUSIONS: Many labels for seizures unexplained by disease are potentially offensive to patients. The search for labels that accurately describe the phenomenon, can be used by patients, doctors and researchers and enhance trust and recovery is worthwhile and amenable to scientific study.

Adolescent↗

The long-term survival of baboon-to-monkey kidney and liver xenografts.

The present study was undertaken to develop an optimum immunosuppressive regimen in baboon-to-monkey life-supporting kidney xenografts. Baseline therapy for all groups include cyclosporine (CsA) and steroids. We compared adding (1) cyclophosphamide (CyP) at dose of 20 mg/kg/day given on post-operative day (POD) 0, 2, 5 and 7; (2) mycophenolic mofetil (MMF) at a dose of 40 mg/kg/day by daily gavage; or (3) CyP + rapamycin (Rap). The latter group was divided into high and low dose subgroups. Untreated xenografts were rejected on POD 6, CsA alone treated xenografts survived for 35 days and CsA + CyP treated xenografts survived for 45 days. Adding MMF significantly prolonged mean survival to 111 +/- 53 days, but the xenografts eventually developed rejection. Combination therapy including CsA, CyP and Rap reliably prevented xenogenic rejection and achieved a mean survival of 290 +/- 30 days. However, high dose CyP + Rap led to high incidence of post-transplant lymphoproliferation disorders (PTLD), while the incidence of PTLD was significantly less in the low dose subgroup (P < 0.01). Four animals in this subgroup survived for more than 300 days with normal renal function and histology. In addition, two liver recipients treated with CsA + CyP survived for 91 and 1,076 days. We conclude that long-term survival of kidney or liver xenografts can be achieved in a non-human concordant xenograft model using currently available immunosuppressive agents.

Animals↗

Unexplained symptoms after terrorism and war: an expert consensus statement.

Twelve years of concern regarding a possible "Gulf War syndrome" has now given way to societal concerns of a "World Trade Center syndrome" and efforts to prevent unexplained symptoms following the most recent war in Iraq. These events serve to remind us that unexplained symptoms frequently occur after war and are likely after terrorist attacks. An important social priority is to recognize, define, prevent, and care for individuals with unexplained symptoms after war and related events (eg, terrorism, natural or industrial disasters). An international, multidisciplinary, and multiinstitutional consensus project was completed to summarize current knowledge on unexplained symptoms after terrorism and war.

Causality↗

Optimizing breast cancer treatment efficacy with intensity-modulated radiotherapy.

PURPOSE: To present our clinical experience using intensity-modulated radiation therapy (IMRT) to improve dose uniformity and treatment efficacy in patients with early-stage breast cancer treated with breast-conserving therapy. METHODS AND MATERIALS: A total of 281 patients with Stage 0, I, and II breast cancer treated with breast-conserving therapy received whole breast RT after lumpectomy using our static, multileaf collimator (sMLC) IMRT technique. The technical and practical aspects of implementing this technique on a large scale in the clinic were analyzed. The clinical outcome of patients treated with this technique was also reviewed. RESULTS: The median time required for three-dimensional alignment of the tangential fields and dosimetric IMRT planning was 40 and 45 min, respectively. The median number of sMLC segments required per patient to meet the predefined dose-volume constraints was 6 (range 3-12). The median percentage of the treatment given with open fields (no sMLC segments) was 83% (range 38-96%), and the median treatment time was <10 min. The median volume of breast receiving 105% of the prescribed dose was 11% (range 0-67.6%). The median breast volume receiving 110% of the prescribed dose was 0% (range 0-39%), and the median breast volume receiving 115% of the prescribed dose was also 0%. A total of 157 patients (56%) experienced Radiation Therapy Oncology Group Grade 0 or I acute skin toxicity; 102 patients (43%) developed Grade II acute skin toxicity and only 3 (1%) experienced Grade III toxicity. The cosmetic results at 12 months (95 patients analyzable) were rated as excellent/good in 94 patients (99%). No skin telengiectasias, significant fibrosis, or persistent breast pain was noted. CONCLUSION: The use of intensity modulation with our sMLC technique for tangential whole breast RT is an efficient method for achieving a uniform and standardized dose throughout the whole breast. Strict dose-volume constraints can be readily achieved resulting in both uniform coverage of breast tissue and a potential reduction in acute and chronic toxicities. Because the median number of sMLC segments required per patient is only 6, the treatment time is equivalent to conventional wedged-tangent treatment techniques. As a result, widespread implementation of this technology can be achieved with minimal imposition on clinic resources and time constraints.

Breast Neoplasms↗

Fatigue.

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Anxiety↗

Somatoform disorders in DSM-V.

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Diagnostic and Statistical Manual of Mental Disord↗

The report of the Chief Medical Officer's CFS/ME working group: what does it say and will it help?

Chronic fatigue syndrome (CFS) sometimes known as myalgic encephalomyelitis or encephalopathy (ME) has long been a controversial topic. This year has seen the publication of a report from an independent working party set up by the UK Chief Medical Officer (CMO) to make recommendations for the management of the condition. The report makes a number of general recommendations about the provision of appropriate care and services. The more controversial issues of what to call the illness, the nature of the illness and what treatment should be recommended are all addressed, but in the form of compromise rather than resolution. To the extent that this report is a step towards highlighting the needs not only of patients with CFS but the larger group of patients with symptom-defined conditions, it is to be welcomed. As a guide to management it raises as many questions as it answers. Much remains to be resolved before guidance that is both evidence based and acceptable to all parties is achieved.

Fatigue Syndrome, Chronic↗