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Biomedical subjects

T Price

Publications and source records attributed to T Price.

At least 19 recordsLinked to original sources

Synchronous bilateral tonsillar carcinoma: role of fluoro-deoxyglucose positron emission tomography scanning in detecting occult primary tumours in metastatic nodal disease of the head and neck.

We present the second case of primary synchronous bilateral tonsillar squamous cell carcinoma reported in the English literature and evaluate the role of fluoro-deoxyglucose positron emission tomography scanning in the search for the occult primary tumour in a patient presenting with metastatic nodal disease in the head and neck.

Carcinoma, Squamous Cell↗

Excess non-spine fractures in women over 50 years with celiac disease: a cross-sectional, questionnaire-based study.

The association of celiac disease with fracture is controversial. Recent studies may have underestimated the impact by studying patients with low fracture risk. Since postmenopausal women are at greatest risk of fracture, we have investigated non-spine fracture occurrence in women > or =50 years with celiac disease. Patients were recruited from hospital and general practice as well as from volunteers, controls from general practice. All completed a questionnaire detailing fracture occurrence. Three hundred and eighty-three female celiac patients and 445 female controls aged > or =50 years at time of study were compared. Mean age was 61.4+/-7.8 years in celiac patients and 62.7+/-9.9 years in controls. Celiac patients were lighter but not shorter. Celiac patients displayed greater "all fracture" prevalence (odds ratio [OR], 1.51; confidence interval [CI], 1.13:2.02) and fracture after 50 years (OR, 2.20; CI, 1.49:3.25). Wrist fracture was more frequent (OR, 1.65; CI, 1.12:2.41), but significance was lost once height and weight were taken into account. Celiac patients had more multiple fractures (OR, 2.96; CI, 1.81:4.83). To investigate the association of fracture with time from diagnosis, 324 celiac patients were paired with a control by age. No excess fracture risk was found more than 10 years before diagnosis amongst celiac patients diagnosed after age 50 years, but risk increased in the period from 10 years before diagnosis to 5 years after and remained high more than 5 years after diagnosis ( p<0.05). Wrist fracture only increased in the period more than 5 years after diagnosis ( p<0.05). In women diagnosed before 50 years, no excess fracture risk existed. Fracture risk in female celiac patients >50 years is increased overall but is related largely to the peri-diagnostic period. Wrist fracture risk is partly accounted for by height and weight, but is more common more than 5 years after diagnosis. Celiac testing may be indicated in thin women over 50 years with multiple fractures, and after diagnosis adequate calcium and vitamin D intake should be ensured.

Age Factors↗

How we do it: The role of trans-nasal flexible laryngo-oesophagoscopy (TNFLO) in ENT: one year's experience in a head and neck orientated practice in the UK.

KEYPOINTS: Transnasal flexible laryngo-oesophagoscopy (TNFLO) is a safe and well-tolerated procedure that may be performed in a procedure room in the outpatient or day-case/main theatre setting. It requires a local anaesthetic and no sedation. It may be used to histologically diagnose or exclude pathology from the nose to the gastro-oesophageal junction. It provides a "one stop" diagnosis service, reducing diagnostic delays, the need for endoscopy under general anaesthesia, barium swallows and follow-up outpatient appointments. Therapeutic procedures such as vocal cord medialization, endolaryngeal laser surgery, insertion of speech prostheses and foreign body removal may be performed without general anaesthesia.

Ambulatory Care↗

Phase II study of capecitabine and mitomycin C as first-line treatment in patients with advanced colorectal cancer.

This study was designed to assess the safety and efficacy of capecitabine and mitomycin C (MMC) in previously untreated patients with advanced colorectal cancer (CRC). Patients received capecitabine 2500 mg m(2) day 1, orally divided in two doses of 1250 mg m(-2) in the morning and evening for 14 days every 21 days and MMC 7 mg m(-2) (maximum total dose 14 mg) as an intravenous bolus every 6 weeks for a total of four courses. The median age was 70 years (range 24-85) and the majority of patients (86.9%) were of performance status 1/2. The most common metastatic site was liver. In all, 84 patients were assessable for response. The overall response rate was 38% (95% CI: 27.7-49.3) and a further 33.3% of patients achieved stable disease over 12 weeks. There was good symptom resolution ranging from 64 to 86%. Grade 3/4 toxicity was as follows: hand-foot syndrome 19.7%; diarrhoea 10%; neutropenia 2.4%; infection 2.3%. Capecitabine and MMC have shown encouraging activity with a favourable toxicity profile, a convenient administration schedule, and could be considered for patients deemed unsuitable for oxaliplatin and irinotecan combinations.

Adult↗

Identification of risk factors for future fracture in patients following distal forearm fracture.

The challenge for healthcare systems around the world is delivering timely preventative strategies to subjects most likely to develop fragility fractures. The success or failure of national campaigns will be determined at local level, and many studies to date have found under-utilization of osteoporosis treatment strategies due to reduced public and healthcare professional awareness. An important link between the at-risk patients and their appropriate therapy is their identification and assessment. In the context of a medium sized secondary care provider, this study examined the efficiency of a nurse-led service for assessing women following distal forearm fracture, looking for additional risk factors for future fracture and also looking at uptake of the assessment programme among the target population. Two hundred and two women, median (range) age 69 (50-91) years presented with distal forearm fracture over a 9-month period. Fifty-four subjects did not participate in the study: they were significantly older than those who did ( P<0.002). One hundred and forty-eight subjects underwent assessment of falls risk, future hip fracture risk and calcaneal ultrasound attenuation measurement: 107 attended for assessment at the hospital and 41 required a health professional to visit at their place of residence-the latter group were significantly older ( P<0.0002). Of 148 subjects assessed, 76 (51%) had one or more risk factors for a fall: these subjects were significantly older ( P<0.0002) and more likely to have required a home visit ( P<0.002). Twenty-seven (18%) were considered at risk of a future hip fracture: again they were older and more likely to have required a home visit ( P<0.0005). Ninety-one subjects (61%) had a calcaneal ultrasound attenuation T-score below -2.0, and were referred for bone densitometry: again, they were older ( P<0.0002) and more likely to have required a home visit ( P<0.05). Bone densitometry demonstrated osteoporosis in 47 (52%) of those with low attenuation, osteopenia in 31 and normal bone density in 13. Of 76 subjects deemed to be at risk of falls, 31 (41%) had osteoporosis demonstrated on bone densitometry and of those at risk of future hip fracture, 12 (44%) had osteoporosis. Only nine (22%) subjects who received home visits had no risk factors for falls or hip fracture and normal bone density, compared to 45 (42%) of those who attended hospital. This study has demonstrated that the efficiency of a program to assess additional risk of future fracture in a population who have already fractured may be influenced by where the assessment is delivered: it may be that the patients at greatest risk did not avail of the service.

Accidental Falls↗

A phase I/II study of oral uracil/tegafur (UFT), leucovorin and irinotecan in patients with advanced colorectal cancer.

BACKGROUND: The aim of this study was to determine the maximum tolerated dose (MTD), toxicity profile and response rate of the oral 5-fluorouracil prodrug UFT (tegafur/uracil) and leucovorin (LV) in combination with irinotecan in patients with advanced or metastatic colorectal cancer. PATIENTS AND METHODS: Patients with histologically proven advanced or metastatic colorectal adenocarcinoma received first-line chemotherapy comprising UFT 250 mg/m(2)/day and LV 90 mg/day given on days 1 to 14, with escalating doses of irinotecan (200-300 mg/m(2)) administered intravenously on day 1 of a three-weekly cycle. Eligibility criteria were standard. The MTD was defined as the dose at which >33% of six patients experienced a dose-limiting toxicity (DLT) during cycle 1. RESULTS: A total of 32 patients were studied. Initially, six patients were treated at each of the irinotecan dose levels (200, 250 and 300 mg/m(2)) combined with UFT 250 mg/m(2)/day and LV 90 mg/day. DLTs consisting of grade 3 or 4 diarrhoea and febrile neutropenia were observed in one of 20 patients at 250 mg/m(2) and three of six patients at the 300 mg/m(2) irinotecan dose level. Having defined the MTD, the 250 mg/m(2) dose level was established as the recommended dose (RD) and expanded to 20 patients in whom treatment was generally well tolerated. The overall response rate was 19%, with five patients having a partial response (PR) and 18 stable disease (SD) out of 32 response-evaluable patients. CONCLUSION: UFT and LV can be safely combined with irinotecan. The RDs for future studies are UFT 250 mg/m(2)/day and LV 90 mg/day given on days 1-14, with irinotecan 250 mg/m(2) administered on day 1, every 3 weeks. This combination is well tolerated and active. Further investigation of UFT and LV in combination with irinotecan is warranted in patients with colorectal cancer.

Adenocarcinoma↗

Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer.

PURPOSE: We report the results of a prospectively randomized study that compared the combination of epirubicin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) (ECF) with the combination of mitomycin, cisplatin, and PVI 5-FU (MCF) in previously untreated patients with advanced esophagogastric cancer. PATIENTS AND METHODS: Five hundred eighty patients with adenocarcinoma, squamous carcinoma, or undifferentiated carcinoma were randomized to receive either ECF (epirubicin 50 mg/m(2) every 3 weeks, cisplatin 60 mg/m(2) every 3 weeks and PVI 5-FU 200 mg/m(2)/d) or MCF (mitomycin 7 mg/m(2) every 6 weeks, cisplatin 60 mg/m(2) every 3 weeks, and PVI 5-FU 300 mg/m(2)/d) and analyzed for survival, response, toxicity, and quality of life (QOL). RESULTS: The overall response rate was 42.4% (95% confidence interval [CI], 37% to 48%) with ECF and 44.1% (95% CI, 38% to 50%) with MCF (P =.692). Toxicity was tolerable, and there were only two toxic deaths. ECF resulted in more grade 3/4 neutropenia and grade 2 alopecia, but MCF caused more thrombocytopenia and plantar-palmar erythema. Median survival was 9.4 months with ECF and 8.7 months with MCF (P =.315); at 1 year, 40.2% (95% CI, 34% to 46%) of ECF and 32.7% (95% CI, 27% to 38%) of MCF patients were alive. Median failure-free survival was 7 months with both regimens. Global QOL scores were better with ECF at 3 and 6 months. CONCLUSION: This study confirms response, survival, and QOL benefits of ECF observed in a previous randomized study. The equivalent efficacy of MCF was demonstrated, but QOL was superior with ECF. ECF remains one of the reference treatments for advanced esophagogastric cancer.

Adult↗

Bilateral simultaneous facial nerve palsy.

Bilateral simultaneous facial nerve palsy is an extremely rare clinical entity with Bell's palsy responsible for a mere 20 per cent of cases. It is, therefore, important that clinicians are aware of the differential diagnosis when evaluating a case.

Adult↗

Abducens nerve palsy as the sole presenting symptom of petrous apicitis.

Petrous apicitis as a potentially fatal complication of suppurative otitis media presents in a variety of forms. Gradenigo's triad of abducens paralysis, deep facial pain due to trigeminal involvement and acute suppurative otitis media rarely occurs. The conflicting symptoms reported in the literature usually result in the delayed recognition of the condition with potentially disastrous consequences. The VIth nerve palsy is considered to be the least reliable sign as it is least often present. We present a case in which it was the sole presenting symptom.

Abducens Nerve Diseases↗

Silent MRI infarcts and the risk of future stroke: the cardiovascular health study.

BACKGROUND: Silent infarcts are commonly discovered on cranial MRI in the elderly. OBJECTIVE: To examine the association between risk of stroke and presence of silent infarcts, alone and in combination with other stroke risk factors. METHODS: Participants (3,324) in the Cardiovascular Health Study (CHS) without a history of stroke underwent cranial MRI scans between 1992 and 1994. Silent infarcts were defined as focal lesions greater than 3 mm that were hyperintense on T2 images and, if subcortical, hypointense on T1 images. Incident strokes were identified and classified over an average follow-up of 4 years. The authors evaluated the risk of subsequent symptomatic stroke and how it was modified by other potential stroke risk factors among those with silent infarcts. RESULTS: Approximately 28% of CHS participants had evidence of silent infarcts (n = 923). The incidence of stroke was 18.7 per 1,000 person-years in those with silent infarcts (n = 67) compared with 9.5 per 1,000 person-years in the absence of silent infarcts. The adjusted relative risk of incident stroke increased with multiple (more than one) silent infarcts (hazard ratio 1.9 [1.2 to 2.8]). Higher values of diastolic and systolic blood pressure, common and internal carotid wall thickness, and the presence of atrial fibrillation were associated with an increased risk of strokes in those with silent infarcts (n = 53 strokes). CONCLUSION: The presence of silent cerebral infarcts on MRI is an independent predictor of the risk of symptomatic stroke over a 4-year follow- up in older individuals without a clinical history of stroke.

Aged↗

Evolutionary genetics: the evolution of plumage patterns.

The identification and sequencing of a gene affecting melanin production in the bananaquit, a bird species notable for its polymorphic plumage colour, paves the way for much greater understanding of the evolution of plumage patterns in birds, and the developmental modulations involved in producing new patterns.

Animals↗

Direct retroviral delivery of human cytochrome P450 2B6 for gene-directed enzyme prodrug therapy of cancer.

Human cytochrome P450 2B6 (CYP2B6) metabolizes the prodrug cyclophosphamide (CPA) to produce phosphoramide mustard that cross-links DNA leading to cell death. We have constructed a novel retroviral vector encoding CYP2B6 (designated "MetXia-P450") and used it to transduce the human tumor cell lines HT29 and T47D. MetXia-P450 transduction sensitised these cells to the cytotoxic effects of the prodrug CPA. Results from in vitro experiments demonstrated adverse effects on the clonogenic survival of cyclophosphamide-treated cells transduced with MetXia-P450. Cytotoxic activity accompanied by bystander effect was particularly evident in 3-D multicellular spheroid models suggesting that this in vitro system may be a more appropriate model for assessing the efficacy of gene directed-enzyme prodrug therapy (GDEPT). We have applied this approach in a clinically relevant gene therapy protocol on established subcutaneous tumor xenografts. These studies show for the first time the efficacy of a P450-based GDEPT strategy mediated by a direct retroviral gene transfer in vivo.

Animals↗

Improving standards in the treatment of acute otitis externa by the use of a treatment protocol and open access to aural toilet.

A prospective audit of the procedure and outcome in the management of acute otitis externa was undertaken in our unit. The first cycle demonstrated a heterogeneous approach and clinical isolation of junior staff. A questionnaire survey of local general practitioners highlighted clinical confusion over the use of topical medication and a need for improved access to facilities for aural toilet. General practitioner liaison and education was an essential component in formulating a change in practice. In particular, open access for aural toilet was introduced and utilization encouraged. Following changes in practice, the second cycle of the audit showed that treatment protocols were effective and adhered to by junior staff.

Acute Disease↗

Analysis of 4070A envelope levels in retroviral preparations and effect on target cell transduction efficiency.

A number of stable producer cell lines for high-titer Mo-MuLV vectors have been constructed. Development has previously centered on increasing end-point titers by producing maximal levels of Mo-MuLV Gag/Pol, envelope glycoproteins, and retroviral RNA genomes. We describe the production yields and transduction efficiency characteristics of two Mo-MuLV packaging cell lines, FLYA13 and TEFLYA. Although they both produce 4070A-pseudotyped retroviral vectors reproducibly at >1 x 10(6) LFU ml(-1), the transduction efficiency of unconcentrated and concentrated virus from FLYA13 lines is poor compared with vector preparations from TEFLYA lines. A powerful inhibitor of retroviral transduction is secreted by FLYA13 packaging cells. We show that the inhibitory factor does not affect transduction of target cells by RD114-pseudotyped vectors. This suggests that the inhibitory factor functions at the level of envelope-receptor interactions. Phosphate starvation of target cells shows a two-fold increase in Pit2 receptor mRNA and causes some improvement in FLYA13 virus transduction efficiency. Western blots show that FLYA13 viral samples contain an eight-fold higher ratio of 4070A envelope to p30gag than that of virus produced by TEFLYA producer cell lines. This study correlates overexpression of 4070A envelope glycoprotein in retroviral preparations with a reduction of transduction efficiency at high multiplicities of infection. We suggest that TEFLYA packaging cells express preferable levels of 4070A compared with FLYA13, which not only enables high-titer stocks to be generated, but also facilitates a high efficiency of transduction of target cells.

Animals↗

A clinical nomogram for predicting long-term survival in advanced colorectal cancer.

From our prospectively accrued database of patients with gastrointestinal cancer, 1057 patients with advanced colorectal cancer were identified with the aim of determining predictive factors for survival of greater than 2 years and to use this information to develop a predictive nomogram. Patient's baseline characteristics, type and number of chemotherapy regimens received, and response to chemotherapy were assessed by univariate and multivariate logistic regression comparing those who survived greater than or less than 2 years. A total of 161 (15.2%) patients survived more than 2 years, so-called long survivors (LS). In multivariate analysis, positive predictive factors for LS were: good performance status (PS), normal serum carcinoembryonic antigen (CEA), rectal primary, Dukes' stage A-B, well or moderate differentiation, two or less disease sites, response to chemotherapy and treatment used protracted venous infusion (PVI) 5-fluorouracil (5-FU) in first-line chemotherapy, and the increasing number of chemotherapy treatments received. From these PS, CEA, number of sites and response to first-line chemotherapy were used to develop a nomogram capable of predicting the probability of survival beyond 2 years for an individual patient. This large study confirmed the relevance of known prognostic factors in metastatic colorectal cancer and demonstrated the importance of response to chemotherapy as an independent factor to predict LS. By combining these, we developed a nomogram which provides information which is likely to prove useful in the management of patients with advanced colorectal cancer.

Adolescent↗

Paradoxical emboli after central venous catheter removal.

Central venous catheters are widely used in intensive medicine to provide blood product, nutritional and antibiotic support. A 45-year-old man with an unsuspected patent foramen ovale underwent a bone marrow allograft for poor-risk acute lymphoblastic leukaemia. His venous line was removed because of probable infection, and he simultaneously sustained a myocardial infarct and a cerebrovascular accident. He made a good recovery from both, but subsequently died of relapsed disease. Appropriate pre-transplant screening investigations are discussed, and the differential diagnosis of this complication in the bone marrow transplant setting.

Bone Marrow Transplantation↗