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Biomedical subjects

J Haviland

Publications and source records attributed to J Haviland.

10 recordsLinked to original sources

High dose chemotherapy and autologous stem cell transplantation as adjuvant therapy for primary breast cancer patients with four or more lymph nodes involved: long-term results of an international randomised trial.

BACKGROUND: The purpose of this study was to assess whether a short course of anthracycline containing chemotherapy followed by high dose therapy with autologous stem-cell support improves disease-free and overall survival as compared with conventional, anthracycline containing chemotherapy, in patients with primary breast cancer and four or more histologically involved lymph nodes. PATIENTS AND METHODS: Two hundred and eighty one patients entered into a randomised clinical trial were allocated to receive standard, conventional treatment (5-fluorouracil, epirubicin and cyclophosphamide-FEC for six cycles) or FEC for three cycles followed by high dose therapy consisting of cyclophosphamide, thiotepa and carboplatin and stem cell rescue (HDT). To be eligible, patients had to be free of overt metastatic disease and be < or =60 years of age. Analyses were according to intention to treat. RESULTS: At a median follow up of 68 months, 118 patients have experienced a relapse or death from breast cancer (62 in the FEC followed by HDT arm and 56 in the conventional FEC arm) and a total of 100 patients have died (54 in the FEC followed by HDT arm and 46 in the conventional FEC arm). No significant difference was observed in relapse-free survival [hazard ratio 1.06, 95% CI 0.74-1.52, p = 0.76] or overall survival [hazard ratio 1.18, 95% CI 0.80-1.75, p = 0.40]. Five patients died from treatment related causes, three as a consequence of HDT and two in the conventional FEC arm. CONCLUSIONS: At the present time, no benefit has been observed from replacing three cycles of conventional chemotherapy with the HDT regimen described here. Patients should continue to receive conventional chemotherapy as adjuvant therapy for breast cancer.

Adult↗

A cancer research (UK) randomized phase II study of idoxifene in patients with locally advanced/metastatic breast cancer resistant to tamoxifen.

Idoxifene is a novel selective oestrogen receptor modulator (SERM) which had greater binding affinity for the oestrogen receptor (ER) and reduced agonist activity compared with tamoxifen in preclinical studies. In a randomized phase II trial in 56 postmenopausal patients with progressive locally advanced/metastatic breast cancer we assessed whether idoxifene showed evidence of activity compared with an increased 40 mg/day dose of tamoxifen in patients who had previously demonstrated resistance to the standard 20 mg/day dose of tamoxifen. Of 47 patients eligible for response (25 idoxifene, 22 tamoxifen), two partial responses and two disease stabilizations (SD) for >6 months were seen with idoxifene (overall clinical benefit rate 16%, 95% CI 4.5-36.1%). The median duration of clinical benefit was 9.8 months. In contrast, no objective responses were seen with the increased 40 mg/day dose of tamoxifen, although two patients had SD for 7 and 14 months (clinical benefit rate 9%, 95% CI 1.1-29.2%). Idoxifene was well tolerated and the reported possible drug-related toxicities were similar in frequency to those with tamoxifen (hot flushes 13% vs 15%, mild nausea 20% vs 15%). Endocrine and lipid analysis in both groups showed a similar significant fall in serum follicle-stimulating hormone and luteinizing hormone after 4 weeks, together with a significant rise in sex hormone binding globulin levels and 11% reduction in serum cholesterol levels. In conclusion, while idoxifene was associated with only modest evidence of clinical activity in patients with tamoxifen-resistant breast cancer, its toxicity profile and effects on endocrine/lipid parameters were similar to those of tamoxifen.

Adult↗

Older patients' experiences of treatment for colorectal cancer: an analysis of functional status and service use.

Age and ageing are an important part of the context within which the care and treatment of people with cancer is provided. More information is needed about the effects of cancer treatment on the lives of older people following inpatient care. We conducted a 3-year study in which older people with colorectal cancer completed a detailed questionnaire on multidimensional function and service use before and after elective treatment. Here we present an analysis of changes in functional status and service use over the pre- to post-treatment period, and set out a detailed picture of older people's experiences before and after treatment. In total, 337 patients with colorectal adenocarcinoma aged 58-95 years were interviewed before treatment using the OARS Multidimensional Functional Assessment Questionnaire (OMFAQ), Rotterdam Symptom Checklist (RSCL) and a severity of morbidity score. Study end points were defined as post-treatment functional status, symptom distress, severity of morbidity and frequency of service use. Pre- and post-treatment data were compared using matched analyses. Logistic regression was used to assess associations between age and the main outcome measures, and frequency of service use after treatment was compared between age groups using the chi2 test. Overall, patients experienced both positive and negative outcomes following treatment. It was notable that patients aged > or = 75 years showed improvement in only one of the principal outcome measures. Patterns of service use following treatment suggest that support at home is a key issue for patients. With the exception of nursing care, however, help at home is provided on a majority of occasions by families themselves. This raises important questions about how much preparation patients and families receive or would like before they leave hospital after treatment for cancer. A collaborative, family-centred approach to meeting people's needs is called for in the months following inpatient care.

Adenocarcinoma↗

Treatment decisions in older patients with colorectal cancer: the role of age and multidimensional function.

The aim of the study was to investigate the role of age and multidimensional functional status in treatment decisions in older patients with colorectal cancer. Three hundred and thirty-seven patients aged 58-95 years with adenocarcinoma of the colon or rectum were interviewed before and after treatment using the OARS Multidimensional Functional Assessment Questionnaire (OMFAQ), a self-reported severity of morbidity scale, and the Rotterdam Symptom Checklist (RSCL). The OMFAQ rates five dimensions of function: social resources, economic resources, mental and physical health and self-care capacity. The likelihood of patients with Duke's C colorectal cancer receiving adjuvant chemotherapy decreased significantly with age (P = 0.001, trend). Differences in treatment received were not explained by differences in morbidity, economic, mental or physical function, self-care capacity, or any of the RSCL measures. After controlling for age, Duke's C patients who received adjuvant chemotherapy were less impaired in social resources than Duke's C patients who did not (P = 0.06). No other significant pre-treatment differences in functional status were found. Differences in age and social resources exist between patients who do and do not receive adjuvant chemotherapy. Care should be taken to ensure that patients are not excluded from treatment with known survival benefits because of their age, and the question of providing appropriate social support during adjuvant chemotherapy should be re-examined.

Adenocarcinoma↗

Expression of the complement anaphylatoxin C3a and C5a receptors on bronchial epithelial and smooth muscle cells in models of sepsis and asthma.

The presence of the complement-derived anaphylatoxin peptides, C3a and C5a, in the lung can induce respiratory distress characterized by contraction of the smooth muscle walls in bronchioles and pulmonary arteries and aggregation of platelets and leukocytes in pulmonary vessels. C3a and C5a mediate these effects by binding to their specific receptors, C3aR and C5aR, respectively. The cells that express these receptors in the lung have not been thoroughly investigated, nor has their expression been examined during inflammation. Accordingly, C3aR and C5aR expression in normal human and murine lung was determined in this study by immunohistochemistry and in situ hybridization. In addition, the expression of these receptors was delineated in mice subjected to LPS- and OVA-induced models of inflammation. Under noninflamed conditions, C3aR and C5aR protein and mRNA were expressed by bronchial epithelial and smooth muscle cells of both human and mouse lung. C3aR expression increased significantly on both bronchial epithelial and smooth muscle cells in mice treated with LPS; however, in the OVA-challenged animals only the bronchial smooth muscle cells showed increased C3aR expression. C5aR expression also increased significantly on bronchial epithelial cells in mice treated with LPS, but was not elevated in either cell type in the OVA-challenged mice. These results demonstrate the expression of C3aR and C5aR by cells endogenous to the lung, and, given the participation of bronchial epithelial and smooth muscle cells in the pathology of diseases such as sepsis and asthma, the data suggest a role for these receptors during lung inflammation.

Aerosols↗

Lung cancer health care needs assessment: patients' and informal carers' responses to a national mail questionnaire survey.

The objective of this study was to describe patients' and informal carers' perceptions of care received and services offered following a diagnosis of primary lung cancer. We prepared a prospective, national, mail questionnaire survey of 466 patients with a diagnosis of primary lung cancer and a lay carer of their choice. The setting was 24 randomly chosen hospitals throughout the UK, from a range of urban (n = 11) and rural settings (n = 13). The majority (76%/159) of responders were recipients of care from cancer units. Two hundred and nine patients (45%) with primary lung cancer and 70 (15%) lay carers completed questionnaires. The main results that we found were that key areas of unmet need were most apparent during periods away from acute service sectors, with as few as 40% of patients reporting having received as much help as they needed from community services. The greatest onus of care for patients fell to lay carers, but only 29% of patients identified their lay carers as having needs in relation to their illness. Where patients received all their diagnostic tests in one hospital they were significantly more likely to wait less time between first seeing their general practitioner (GP) and being told their diagnosis (P = 0.0001) than patients who had to attend more than one hospital during their diagnostic work-up period. Fifty per cent of patients reported experiencing some degree of breathlessness even at rest, but only 15% reported having received any advice on living with it. Less than a quarter (23%) of hospital consultants identified anxiety as a key problem for patients with lung cancer, but 66% of patients identified it as such. Hospital staff largely overlook the needs of informal carers, who derive support from a small, mainly community oriented group of professionals, but accessing help is problematic and is dependent on local resources and a need to be proactive. Our conclusions are that developments in service provision for patients with lung cancer and their informal carers need to focus on six key areas: development of strategies to encourage patients to present earlier to their GP; ongoing evaluation of rapid diagnostic clinics; development and evaluation of a lung cancer care coordinator role; evaluation of innovations in delivery of nursing care in the community; development of local guidelines to facilitate equitable access to palliative care and social services; and evaluation of supportive strategies targeted at lay carers.

Adult↗

Outcome after severe non-accidental head injury.

Over the past three years 15 children have been admitted to the paediatric intensive care unit (PICU) at Addenbrooke's hospital suspected of having non-accidental injuries; presentation was diverse and often mild and out of proportion to the degree of morbidity seen at discharge and follow up. When compared with a group of similar aged children admitted to the PICU with severe head injury caused by accidental impact trauma, the differences in morbidity were profound. It is suggested that these differences are explained in part by the predominant repetitive rotational forces experienced during severe shaking compared with the translocational forces that the head experiences during impact injuries. This anecdotal evidence supports the theory that shaking alone may cause severe intracranial injury. Thus campaigns should continue to increase public and doctors' awareness that shaking may be dangerous.

Accidents↗

A retrospective evaluation of 51 cases of peripheral nerve sheath tumors in the dog.

Fifty-one cases of canine peripheral nerve sheath tumors were reviewed. Signalment, presenting clinical signs, duration of clinical signs, physical and neurological examination findings, results of diagnostic procedures, type of surgery performed, tumor location, relapse-free intervals and survival times, and causes of death were evaluated. Tumors were divided into three anatomical groups: tumors involving nerves distal to the brachial or lumbosacral plexus (Peripheral Group), tumors involving nerves of the brachial or lumbosacral plexus (Plexus Group), and tumors involving the vertebral canal (Root Group). The most common clinical findings were unilateral forelimb lameness and muscle atrophy. The most useful diagnostic tests were myelography and electromyography. Although there was no significant difference, dogs in the Root Group tended to have shorter relapse-free intervals and survival times than dogs in the Plexus Group. The overall prognosis for surgical management of peripheral nerve sheath tumors is guarded to poor.

Animals↗