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Biomedical subjects

P Allen

Publications and source records attributed to P Allen.

At least 19 recordsLinked to original sources

The use of cultured epithelial autograft in the treatment of major burn wounds: eleven years of clinical experience.

INTRODUCTION: In patients with burns involving over 50% total body surface area (TBSA), donor skin is limited. Tissue engineering, particularly cultured epithelial autograft (CEA), offers a potential solution to assist in expedient wound closure. MATERIALS AND METHODS: Prior to 1994, the application of CEA was restricted to confluent cell sheets. The introduction of an autologous cell suspension (CellSpray) in 1994 enabled cells to be delivered to the wound via aerosol onto debrided burn and donor skin graft wound areas. This retrospective clinical audit of major burn injured patients (n=84) describes the use of CEA in those with over 50%TBSA in Western Australia (WA) between 1992 and 2002. RESULTS: The initial introduction of CEA was as confluent sheets, as this evolved to the use of CEA in suspension there was a reduction in the required surgical intervention and total length of stay (TLOS) divided by %TBSA. DISCUSSION: With the audit covering an 11-year period, many facets of clinical burn care have evolved. The WA experience has demonstrated CEA has been positively integrated into clinical practice in association with traditional wound care techniques of skin grafting to augment wound healing.

Adult↗

The use of cultured epithelial autograft in the treatment of major burn injuries: a critical review of the literature.

INTRODUCTION: The need to achieve rapid wound closure in patients with massive burns and limited skin donor sites led to the investigation of in vitro cellular expansion of keratinocytes. The use of cultured epithelial autografts (CEA) was first reported in the treatment of major burns in 1981. Since that time, support for the use of CEA has varied, ranging from 'a useful agent' to having 'no demonstrable effect on the outcome of extensively burned patients'. METHODS: This critical review of the literature examines issues associated with the use of CEA and the introduction of the technology into clinical practice. The factors potentially limiting the use of cultured CEA are the time necessary to culture CEA sheets, the reliability of 'take', vulnerability of grafts on the newly healed surface, long-term durability and the cost implications of such treatment. The available literature was located and critically evaluated using the Australian National Health and Medical Research Council Guidelines. FINDINGS: In the identified literature, the level of evidence to support the use of CEA in major burn injures is limited and often restricted to case studies and case series with no Level 1 evidence currently available. CONCLUSION: The main question arising 'Does CEA have a role in the treatment of major burns?' has proven difficult to answer due to the wide variation in both the quality of study design and the findings. At best, the literature review has highlighted areas of concern that have hindered the successful use of CEA. Our review critically evaluates the use of CEA and explores the advances in techniques towards attempting to improve reliable clinical implementation of CEA. The need for higher level research into the use of CEA is emphasised by this review.

Burns↗

Development of a computed tomographic calibration method for the determination of lean meat content in pig carcasses.

Sixty left sides of pig carcasses were scanned by spiral computed tomography (CT) to measure lean meat weight and percentage. The carcasses were fully dissected and scanned to develop a calibration protocol. Different image analyses were performed on the basis of anatomically defined scans, direct volumetric estimation, body- and grey-scale ranges and using Partial Least Squares (PLS) regression of data provided by CT. The R2 values of the calibrations for lean meat weight were 0.874, 0.976, 0.983 and 0.992, respectively, depending on the method applied. The PLS proved to be the best approach with a calibration RSD of 232 g. When changing from lean meat weight to percentage, the statistical goodness drops-to a very small extent (R2 = 0.988, RSD = 0.56). According to the results, the CT method can be recommended as a reference for determining the lean meat content of pig carcasses.

Adipose Tissue↗

Postoperative radiotherapy increases locoregional control of patients with stage IIIA non-small-cell lung cancer treated with induction chemotherapy followed by surgery.

PURPOSE: To determine the effectiveness of postoperative radiotherapy (RT) in patients with Stage IIB and Stage IIIA non-small-cell lung cancer (NSCLC) treated with induction chemotherapy followed by surgery. METHODS AND MATERIALS: We retrospectively reviewed the treatment records of 98 patients (58 men and 40 women; median age 61 years, range 31-91) with Stage IIB and Stage IIIA NSCLC who were treated with induction chemotherapy followed by surgery at our institution between January 1990 and December 2000. Patients were grouped by treatment (chemotherapy/surgery alone vs. chemotherapy/surgery/RT), by disease stage and nodal classification. The rates of local control (LC), disease-specific survival, disease-free survival, and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: Of the 98 patients, 40 had Stage IIB and 58 had Stage IIIA. The clinical disease stage and N stage were significantly greater in those patients who underwent RT than in those who did not; however, no statistically significant differences were identified in the additional characteristics between those receiving and not receiving RT within each stage or nodal group. The overall 5-year actuarial LC rate was 81% in the RT group and 54% in the chemotherapy/surgery-alone group (p = 0.07). Postoperative RT significantly improved the 5-year LC rate in patients with Stage IIIA disease (from 35% to 82%, p = 0.01). Postoperative RT did not significantly improve the 5-year OS rate (30% with RT vs. 49% without) for all patients or for patients with Stage IIIA disease. The disease-specific survival and disease-free survival rates did not differ between the treatment groups. Patients who responded to induction chemotherapy had a significantly greater 5-year OS rate (49%) than did those with stable or progressive disease (22%, p = 0.003). CONCLUSION: Postoperative RT in patients with Stage IIIA NSCLC treated with induction chemotherapy followed by surgery significantly improved LC without improving OS. Significantly improved survival was observed in all patients who responded to induction chemotherapy compared with those with stable or progressive disease.

Adenocarcinoma↗

The funding and organization of infection control in NHS hospital trusts: a study of infection control professionals' views.

The problems associated with hospital-acquired infection have been causing increasing concern in England in recent years. This paper reports the results of a nationwide survey of hospital infection control professionals' views concerning the organizational structures used to manage and obtain funding for control of infection. A complex picture with significant variation between hospitals emerges. Although government policy dictates that specific funding for hospital infection control is formally made available, it is not always the case that infection control professionals have adequate resources to undertake their roles. In some cases this reflects the failure of hospitals' infection control budgetary mechanisms; in others it reflects the effects of decentralizing budgets to directorate or ward level. Some use was made of informal mechanisms either to supplement or to substitute for the formal ones. But almost all infection control professionals still believed they were constrained in their ability to protect the hospital population from the risk of infectious disease. It is clear that recent government announcements that increased effort will be made to support local structures and thereby improve the control of hospital acquired infection are to be welcomed.

Attitude of Health Personnel↗

Early vascular abnormalities and de novo nitrate tolerance in diabetes mellitus.

OBJECTIVE: The haemodynamic consequence of altered mechanical wall properties in diabetes can impair the compliance characteristics or pulsatile function of arteries before changes in calibre or peripheral resistance become evident. We studied the sensitivity of pulsatile and steady-state haemodynamic variables in identifying vascular abnormalities and assessing arterial responsiveness to glyceryl trinitrate (GTN) in patients with diabetes, free from clinical complications of the disease. METHODS: Radial artery pressure waveforms were recorded in 22 patients with diabetes and 22 age- and sex-matched control subjects, using a calibrated tonometer device. A computer-based assessment of the diastolic pressure decay was used to quantify changes in arterial waveform morphology in terms of pulsatile (arterial compliance) and steady-state (peripheral resistance) haemodynamics. Pressure pulse waveforms were recorded before and 3, 6 and 9 min after the administration of 300 micro g of GTN. RESULTS: Of the pulsatile and steady-state impedance parameters, only small artery compliance was significantly different in patients, 4.7 ml/mmHg (95% CI 3.8-5.8), compared with control subjects 7.1 ml/mmHg (95% CI 5.4-8.7); (p < 0.05). In response to GTN small artery compliance increased, and systemic vascular resistance decreased significantly in control subjects; (p < 0.05) but remained unchanged in patients with diabetes. CONCLUSIONS: Arterial waveform analysis proved more sensitive in detecting early vascular abnormalities and tracking the haemodynamic effects of GTN in patients with diabetes than changes in total peripheral resistance. The diminished responsiveness of the arterial vasculature to organic nitrates may have therapeutic implications for the treatment of cardiovascular disease in diabetes mellitus.

Adult↗

Randomized phase III study of chemoradiation with or without amifostine for patients with favorable performance status inoperable stage II-III non-small cell lung cancer: preliminary results.

A prospective randomized study was conducted to determine whether amifostine (Ethyol) reduces the rate of severe esophagitis and hematologic and pulmonary toxicity associated with chemoradiation or improves control of non-small cell lung cancer (NSCLC). Sixty patients with inoperable stage II or III NSCLC were treated with concurrent chemoradiotherapy. Both groups received thoracic radiation therapy (TRT) with 1.2 Gy/fraction, 2 fraction per day, 5 days per week for a total dose 69.6 Gy. All patients received oral etoposide (VP-16), 50 mg Bid, 30 minutes before TRT beginning day 1 for 10 days, repeated on day 29, and cisplatin 50 mg/m(2) intravenously on days 1, 8, 29, and 36. Patients in the study group received amifostine, 500 mg intravenously, twice weekly before chemoradiation (arm 1); patients in the control group received chemoradiation without amifostine (arm 2). Patient and tumor characteristics were distributed equally in both groups. Of the 60 patients enrolled, 53 were evaluable (27 in arm 1, 26 in arm 2) with a median follow-up of 6 months. Median survival times were 26 months for arm 1 and 15 months for arm 2, not statistically significantly different. Morphine intake to reduce severe esophagitis was significantly lower in arm 1 (2 of 27, 7.4%) than arm 2 (8 of 26, 31%; P =.03). Acute pneumonitis was significantly lower in arm 1 (1 of 27, 3.7%) than in arm 2 (6 of 26, 23%; P =.037). Hypotension (20 mm Hg decrease from baseline blood pressure) was significantly more frequent in arm 1 (19 of 27, 70%) than arm 2 (1 of 26, 3.8%; P =.0001). Only 1 patient discontinued treatment because of hypotension. These preliminary results showed that amifostine significantly reduced acute severe esophagitis and pneumonitis. Further observation is required to assess long-term efficacy.

Adult↗

Effective pelvic symptom control using initial chemoradiation without colostomy in metastatic rectal cancer.

PURPOSE: To assess pelvic chemoradiotherapy (CXRT) without colostomy as a component of the multidisciplinary management of patients presenting with metastatic rectal cancer. METHODS AND MATERIALS: Eighty patients with synchronous distant metastases from rectal cancer were treated with initial CXRT. Hypofractionated radiotherapy was administered usually with concurrent 5-FU (92%, 300 mg/m(2)/day, M-F). Three-field belly-board technique was used in 89%. Group 1 had CXRT alone (n = 55). Group 2 (n = 25) patients were selected for primary disease resection, and sometimes HAI chemotherapy (n = 10) or hepatic resection (n = 5). Subsequently, 78% received systemic chemotherapy. RESULTS: Symptoms from primary tumor resolved in 94%. Endoscopic complete clinical response rate was 36%. Two-year survival (11% vs. 46%, p < 0.0001) and symptomatic pelvic control (PC, 81% vs. 91%, p = 0.111) were higher in Group 2, but colostomy-free rate (CFR) was lower (79% vs. 51% p = 0.02). CFR was 87% in Group 1 patients managed initially without fecal diversion (n = 50). Examining all patients using multivariate analysis, pelvic pain at presentation (p < 0.00001), BED (biologic equivalent dose at 2 Gy/fraction) < 35 Gy (p = 0.077), and poor differentiation (0.079) predicted worse PC. Poor differentiation (p = 0.017) and selection for CXRT alone (p < 0.0001) predicted worse survival. There were 4 RTOG of Grade 3 or greater acute complications, 5 severe perioperative complications, and no significant late treatment-related complications. CONCLUSION: Durable PC can be safely achieved without colostomy in most patients presenting with primary rectal cancer and synchronous systemic metastases using hypofractionated pelvic chemoradiation. A BED greater than 35 Gy is recommended. Selected patients appear to benefit from resection of primary disease. Higher doses should be investigated in patients with pelvic pain.

Adult↗

Event-related fMRI with simultaneous and continuous EEG: description of the method and initial case report.

We report on the initial imaging findings with a new technique for the simultaneous and continuous acquisition of functional MRI data and EEG recording. Thirty-seven stereotyped interictal epileptiform discharges (spikes) were identified on EEG recorded continuously during the fMRI acquisition on a patient with epilepsy. Localization of the BOLD activation associated with the EEG events was consistent with previous findings and EEG source modeling. The time course of activation was comparable with the physiological hemodynamic response function (HRF). The new methodology could lead to novel and important applications in many areas of neuroscience.

Cerebrovascular Circulation↗

S100 expression in cutaneous scars: a potential diagnostic pitfall in the diagnosis of desmoplastic melanoma.

AIMS: The histological distinction of desmoplastic melanoma from cutaneous scar tissue, particularly in the context of re-excision specimens or possible recurrence, may be very difficult. Immunostaining for S100 protein is often used to discriminate although there are little data on S100 expression in scar tissue. The aim of this study was to assess whether S100-positive cells are present in dermal scars and, if so, their extent, distribution and nature. METHODS AND RESULTS: Twenty-two re-excision specimens of previously biopsied nonmelanocytic skin lesions were reviewed. Formalin-fixed paraffin-embedded sections containing dermal scars were stained by a standard ABC immunoperoxidase technique for S100 protein, CD1a and neurofilaments. The distribution and morphology of positive cells within the dermal scar tissue were documented. Cells expressing S100 protein were identified within the scars of 21 of the 22 cases. The number of S100-positive cells varied between cases but in four specimens was substantial. They displayed a variety of morphological appearances but the majority were spindle-shaped. A few showed mild cytological atypia. It is suggested that the majority represent Schwann cells with a minority of Langerhans cells and cells of uncertain lineage. CONCLUSION: S100-positive cells, including spindle cells showing mild atypia, are found in cutaneous scars. S100 staining of re-excision specimens or putative recurrences of desmoplastic melanoma should be interpreted with caution.

Antigens, CD1↗

Teens' images of smoking and smokers.

The authors used qualitative and quantitative data to identify and interpret specific images teens have about smoking and smokers. Qualitative data were collected in 1996 from 793 teenagers participating in 125 focus groups at eight different sites across the United States. Most focus groups were homogeneous with respect to gender, ethnicity, and smoking status. Ages ranged from 12 to 18 years, and about half of the participants were female. The majority of participants (62%) were white and African American, the remainder (38%) were Hispanic, American Indian, and Asian/Pacific Islander. Groups were comprised of smoking and nonsmoking teens. Focus group activities were used to elicit image-related discussions about attitudes, beliefs, and perceptions of smoking. Investigators identified seven consistent and distinctive image themes: Appearance (smoking is dirty and unattractive), Activity (nonsmokers have busy, active lives), Drugs and sex (smokers are substance abusers and are sexually active), Rebellion (smokers belong to rebellious groups), Affect (smokers are depressed, angry, and stressed-out), In control (nonsmokers have self-control and are independent), and Pride (nonsmokers are proud of themselves, their families, and their heritage). A large scale, multi-site qualitative research approach can increase understanding of teen smoking. The identification of distinctive images of smoking can help researchers develop more sophisticated models of the processes of teen smoking than currently exist.

Adolescent↗

Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer.

The aim of this study was to determine if the response to preoperative radiation and chemotherapy with continuous infusion 5-fluorouracil (5-FU) was predictive for survival among patients with locally advanced rectal cancer. Preoperative chemoradiation (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-FU (300 mg/m2/day) was given to 117 patients. The pretreatment stage distribution, as determined by endorectal ultrasound (u), included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases; endorectal ultrasound was not performed in 13% of cases (15 patients). Approximately 6 weeks after completion of CTX/XRT, surgery was performed. Adjuvant chemotherapy, consisting of 400 to 425 mg/m2 of 5-FU plus 20 mg/m2 leucovorin for 5 days, was administered every 28 days for 4 to 6 cycles after surgical resection. Among the 74 patients treated with adjuvant chemotherapy, the preoperative stage of disease was 31 with T3N0 and 43 T3N1. Median follow-up was 46 months (range 2 to 89 months). The pathologic tumor stages were Tis-2N0 in 26%, T2N1 in 5%, T3N0 in 21%, T3N1 in 15%, T4N0 in 5%, and T4N1 in 1%; a complete response (CR) to preoperative CTX/XRT was pathologically confirmed in 32 (27%) of patients. Tumor down-staging occurred in 72 (62%) cases. A sphincter-saving procedure (SP) was possible in 59% of patients. The median DFS and overall survival rates for responders were 46 months and 47 months, respectively; for non-responders these outcome measures were 38 months and 41 months, respectively. Log-rank analysis showed that the distant metastatic-free survival rates improved with any response to CTX/XRT (p < 0.00001), CR to CTX/XRT (p < 0.009) and SP (p < 0.012). Likewise, these parameters also significantly influenced DFS rates (CTX/XRT p < 0.00001; CR p < 0.006; and SP p < 0.008). Control of pelvic disease was influenced by clinical size (p < 0.002) and SP (p < 0.016) on univariate analysis. On multivariate analysis only clinical size (p < 0.002) continued to be a significant factor for local control. Factors on multivariate analysis that resulted in significant improvements in cancer-specific survival included any response to preoperative CTX/XRT (p < 0.017) and administration of adjuvant chemotherapy (p < 0.034). Any response to preoperative CTX/XRT improved distant metastatic-free and disease-free survival rates. Multivariate analysis confirmed that a response to preoperative CTX/XRT predicted for improvements in overall survival among patients with locally advanced rectal cancer. Patients who fail to respond to preoperative 5-FU based chemotherapy given concomitantly with radiation have higher rates of distant metastases with adjuvant 5-FU therapy.

Adult↗

Polyether antibiotic CP44,161.

The crystal structure of antibiotic CP44,161, 6-(7-(2-ethyl-2-[5-(1-hydroxymethyl)-5-methyl-2,3,4,5-tetrahydro-2-furyl]-4,10,-12-trimethyl-1,6,8-trioxadispiro[4.1.5.3]pentadec-13-en-9-yl)-4-hydroxy-3,5-dimethyl-6-oxononyl)-2-hydroxy-3-methylbenzoic acid monohydrate, C43H66O10.H2O, has been determined by X-ray crystallography. The molecule adopts a cyclic conformation, with a centrally located water molecule contributing to the stability of the conformation through hydrogen-bonding interactions.

Anti-Bacterial Agents↗