Biomedical subjects

P D Maguire

Publications and source records attributed to P D Maguire.

12 recordsLinked to original sources

PubMed2006

Human microvascular endothelial cellular interaction with atomic N-doped DLC compared with Si-doped DLC thin films.

This article reports results of endothelial cell interaction with atom beam source N-doped a-C:H (diamond-like carbon, DLC) as it compares with that of Si-doped DLC thin films. The RF plasma source exhibits up to 40% N-dissociation and N-atomic fluxes of approximately 0.85 x 10(18) atoms/s, which ensures better atomic nitrogen incorporation. Two different types of nitrogen species (with and without the use of sweep plates to remove charged ions) were employed for nitrogen doping. The number of attached endothelial cells is highest on Si-DLC, followed by the N-DLC (where the sweep plates were used to remove ions), the N-DLC (without the use of sweep plates), undoped DLC, and finally the uncoated sample. The contact angle values for these films suggest that water contact angle is higher in the atomic nitrogen neutral films and Si-DLC films compared to the ionized-nitrogen specie doped films and undoped DLC thin films, suggesting that the more hydrophobic films, semiconducting films, and film with relieved stress have better interaction with human microvascular endothelial cells. It seems evident that N-doping increases the Raman I(D)/I(G) ratios, whereas N-neutral doping decreases it slightly and Si-doping decreases it even further. In this study, lower Raman I(D)/I(G) ratios are associated with increased sp(3)/sp(2) ratio, an increased H concentration, photoluminescence intensity, and a higher endothelial cellular adhesion. These investigations could be relevant to biocompatibility assessment of nanostructured biomaterials and tissue engineering.

Cell Adhesion↗

PubMed2004

Toxic cure: Hyperfractionated radiotherapy with concurrent cisplatin and fluorouracil for Stage III and IVA head-and-neck cancer in the community.

PURPOSE: To evaluate efficacy and toxicity of the Duke University chemoirradiation regimen for locally advanced head-and-neck cancer in a regional community cancer center. METHODS AND MATERIALS: Between June 1998 and June 2002, 50 patients with Stage III or IVA squamous cell carcinoma of the head and neck were treated definitively with concurrent combined modality therapy (CMT). Patients received accelerated, hyperfractionated radiotherapy (AFRT), 1.2-1.25 Gy b.i.d., to a median prescribed dose of 70 Gy. Chemotherapy consisted of cisplatin 12 mg and fluorouracil 600 mg/m(2) daily for 5 consecutive days during Weeks 1 and 6, followed by two cycles after AFRT. Patients with N2-N3 neck disease (n = 21; 42%) were considered for neck dissection depending on their response to AFRT and chemotherapy. Twenty-nine patients with Stage III and IVA disease treated between 1991 and 1997 with definitive RT alone served as historical controls. RESULTS: Forty-nine patients (98%) in the CMT group completed the prescribed AFRT and 38 (76%) completed four cycles of chemotherapy. Three of 8 patients who underwent neck dissection had a pathologically complete response. The median follow-up for all patients was 23 months. The actuarial progression-free survival rate at 2 years was 75% for the CMT group vs. 40% (p <0.01) for the RT group. The overall survival rate was 80% and 43% (p <0.01), respectively, for the CMT and RT groups. Acute Radiation Therapy Oncology Group Grade 3 toxicities for the CMT group were mucosal (n = 50; 100%), skin (n = 9; 18%), and hematologic (n = 3; 6%). Late Grade 3-4 toxicities consisted of pharyngeal stricture (n = 7; 14%), laryngeal chondritis (n = 3; 6%), osteoradionecrosis (n = 2; 4%), and peripheral neuropathy (n = 1; 2%). CONCLUSION: This aggressive regimen of AFRT with concurrent cisplatin and fluorouracil with or without neck dissection is feasible in the community setting for patients with Stage III and IVA head-and-neck cancer. Early results indicated excellent survival, albeit with universal acute mucosal, and considerable, although acceptable, late toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Platelet adhesion on silicon modified hydrogenated amorphous carbon films.

We have investigated the effect of changes in microstructure, surface energy, surface charge condition and electronic conduction on the interaction of human platelets with silicon modified hydrogenated amorphous carbon films (a-C:H:Si or Si-DLC). Results based on Raman spectroscopy, Scanning electron microscopy, X-ray photo-electron spectroscopy, surface energy measurements, electrical resistivity, contact potential difference, and thermal annealing indicates a correlation between some of the measured values and the interaction of the films with human blood platelets. Statistical analysis of platelet aggregation on the films using the Student's t-test indicated differences between platelet aggregation on the modified films compared to the as-deposited film at a p-value of <0.05.

Biocompatible Materials↗

PubMed2001

73.6 Gy and beyond: hyperfractionated, accelerated radiotherapy for non-small-cell lung cancer.

PURPOSE: To assess results with twice-daily high-dose radiotherapy (RT) for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between 1991 and 1998, 94 patients with unresectable NSCLC were prescribed > or = 73.6 Gy via accelerated fractionation. Fifty were on a phase II protocol (P group); 44 were similarly treated off-protocol (NP group). The clinical target volume received 45 Gy at 1.25 Gy bid (6-hour interval). The gross target volume received 1.6 Gy bid to 73.6 to 80 Gy over 4.5 to 5 weeks using a concurrent boost technique. Overall survival (OS) and local progression-free survival (LPFS) were calculated by the Kaplan-Meier method. Median follow-up durations for surviving P and NP patients were 67 and 16 months, respectively. RESULTS: Total doses received were > or = 72 Gy in 97% of patients. The median OS by stage was 34, 13, and 12 months for stages I/II, IIIa, and IIIb, respectively. LPFS was significantly longer for patients with T1 lesions (median, 43 months) versus T2-4 (median, 7 to 10 months; P =.01). Results were similar in the P and NP groups. Acute grade > or = 3 toxicity included esophagus (14 patients; 15%), lung (three patients; 3% [one grade 5]), and skin (four patients; 4%). Grade > or = 3 late toxicity in 86 assessable patients included esophagus (three patients; 3%), lung (15 patients; 17% [three grade 5]), skin (five patients; 6%), heart (two patients; 2%), and nerve (one patient; 1%). CONCLUSION: This regimen yielded favorable survival results, particularly for T1 lesions. Acute grade > or = 3 toxicity seems greater than for conventional RT, though most patients recovered. Late grade > or = 3 pulmonary toxicity occurred in 17%. Because of continued locoregional recurrences, we are currently using doses > or = 86 Gy.

Actuarial Analysis↗

PubMed2000

A new three-dimensional dose distribution reduction scheme for tubular organs.

In tubular structures, spatial aspects of the dose distribution may be important in determining the normal tissue response. Conventional dose-volume-histograms (DVHs) and dose-surface-histograms (DSHs) lack spatial information and may not be adequate to represent the three-dimensional (3D) dose data. A new 3D dose distribution data reduction scheme which preserves its longitudinal and circumferential character is presented. Dose distributions were generated at each axial level for esophagus or rectum in 123 patients with lung cancer or prostate cancer. Dose distribution histograms at each axial level were independently analyzed along the esophageal or rectal circumference to generate dose-circumference-histogram (DCH) sheets. Two types of plots were then generated from the DCH sheet. The first considered the percentage of the circumference at each axial level receiving various doses. The second considered the minimum dose delivered to any percentage of the circumference at each axial level. The DCH as a treatment planning tool can be easily implemented in a 3D planing system and is potentially useful for the study of the relationship between the complication risk and the longitudinal and circumferential dose distributions.

Dose-Response Relationship, Radiation↗

PubMed2000

Gelatinase and inhibitor expression in soft tissue sarcomas: lack of correlation with distant metastasis.

The predominant mode of death for most patients with soft tissue sarcomas (STS) remains distant metastasis (DM). Current clinical predictors of DM are unreliable. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) correlate with biologic aggression in other tumors. The gene expression of the gelatinase, MMP-2 and MMP-9, and their respective inhibitors, TIMP-1 and TIMP-2, in STS was evaluated. Twelve fresh-frozen surgical specimens from patients with large (>5 cm) STS were analyzed. Six patients developed DM while 6 survived disease-free (DFS) at a minimum follow-up of 13 months. Following mRNA isolation, reverse transcription-polymerase chain reaction was performed using primers for MMP-2, MMP-9, TIMP-1, and TIMP-2. Gene expression was determined by band densitometry. Ratios of MMP-9/TIMP-1 and MMP-2/ TIMP-2 gene expression as well as MMP-2 protein activation ratio (active/inactive enzyme determined by gelatin zymography) were analyzed for correlation with DM and DFS. MMP-2 gene was expressed in 12 specimens, while MMP-9 was detectable in 9. Relative levels of MMP-2 and MMP-9, MMP2/TIMP-2 ratio, and MMP-9/TIMP-1 ratio were not significantly correlated with DM. Poor DFS was significantly correlated with high MMP-9/TIMP-1 ratio (p = 0.02). Active MMP-2 protein was detected in 12 specimens, while active MMP-9 protein was detected in 2. No association was found between MMP-2 protein activation ratio and DM or DFS. While MMP-2 gene expression and protein activity occurred in these 12 specimens, gelatinase/inhibitor ratios (for both MMP-2 and MMP-9) appear to be poor predictors of DM in STS.

Disease-Free Survival↗

PubMed2000

Can the cost of permanent prostate implants be reduced? An argument for peripheral loading with higher strength seeds.

PURPOSE: To evaluate the economic impact of higher vs. lower strength permanent radioactive seeds used for prostate brachytherapy in the treatment of localized adenocarcinoma of the prostate. MATERIALS AND METHODS: Treatment plans for 50 patients who received an iodine 125 implant as monotherapy for favorable risk prostate cancer were reviewed and specific activity (mCi/cc) was determined for prostate volumes that ranged from 12 to 87 cc. Current prices for individual model 6711 125I seeds were obtained from the manufacturer (Nycomed/Amersham). Total seed costs for three theoretical prostate implant volumes of 25, 40, and 55 cc were calculated using seed strengths of 0.25, 0.34, 0.50, and 0.75 mCi/seed. RESULTS: Specific activities for prostate volumes of 25, 40, and 55 cc were 1.25, 1.15, and 1.00 mCi/cc, respectively. Total seed cost was inversely related to seed strength. For a 25-cc prostate the cost ranged from $1,890 (0.75 mCi/seed) to $5,625 (0.25 mCi/seed), for a 40-cc prostate $2,745 to $8,280, and for a 55-cc prostate $3,285 to $9,900. For a medium-sized gland (40 cc), the treatment plan using a seed strength of 0.75 mCi/seed resulted in a total seed cost of $2,745 vs. $6,075 for a plan using an activity of 0.34 mCi/seed. This savings of approximately 55% in total seed cost between seed strengths of 0.75 and 0.34 mCi/seed held true for small (25 cc) and large (55 cc) prostate volumes as well. CONCLUSIONS: Given the current prices for 125I individual seeds, prostate implants using a peripheral loading technique with higher activity seeds may result in a significantly lower material cost than techniques using lower activity seeds. However, issues regarding morbidity as well as sensitivity to source placement error need to be addressed further before any final conclusions can be made.

Adenocarcinoma↗

PubMed1999

Clinical and dosimetric predictors of radiation-induced esophageal toxicity.

PURPOSE: To evaluate the incidence, severity, and clinical/dosimetric predictors of acute and chronic esophageal toxicities in patients with non-small cell lung cancer (NSCLC) treated with high-dose conformal thoracic radiation. METHODS AND MATERIALS: Ninety-one patients with localized NSCLC treated definitively with high-dose conformal radiation therapy (RT) at Duke University Medical Center (DUMC) were reviewed. Patient characteristics were as follows: 53 males and 38 females; median age 64 yr (range 46-82); stage I--16, II--3, IIIa--40, IIIb--30, X--2; dysphagia pre-RT--6 (7%). Treatment parameters included: median corrected dose-78.8 Gy (range 64.2-85.6); BID fractionation-58 (64%); chemotherapy-43 (47%). Acute and late esophageal toxicities were graded by RTOG criteria. Using 3D treatment planning tools, the esophagus was contoured in a uniform fashion, the 3D dose distribution calculated (with lung density correction), and the dose-volume (DVH) and dose-surface histograms (DSH) generated. At each axial level, the percentage of the esophageal circumference at each dose level was calculated. The length of circumferential esophagus and the maximum circumference treated to doses >50 Gy were assessed. Patient and treatment factors were correlated with acute and chronic esophageal dysfunction using univariate and multivariate logistic regression analyses. RESULTS: There were no acute or late grade 4 or 5 esophageal toxicities. Ten of 91 patients (11%) developed grade 3 acute toxicity. On univariate analysis of clinical parameters, both dysphagia pre-RT (p = 0.10) and BID fractionation (p = 0.11) tended toward significantly predicting grade 3 acute esophagitis. None of the dosimetric parameters analyzed significantly predicted for grade 3 acute esophagitis. Twelve of 66 assessable patients (18%) developed late esophageal toxicity. Of the clinical parameters analyzed, only dysphagia pre-RT (p = 0.06) tended toward significantly predicting late esophageal toxicity. On univariate analyses, the effects of percent organ volume treated >50 Gy (p = 0.05), percent surface area treated >50 Gy (p = 0.05), length of 100% circumference treated >50 Gy (p = 0.04), and maximum percent of circumference treated >80 Gy (p = 0.01) significantly predicted for late toxicity of all grades. On multivariate analysis, percent organ volume treated >50 Gy (p = 0.02) and maximum percent of circumference treated >80 Gy (p = 0.02) predicted for late toxicity. CONCLUSIONS: Late esophageal toxicity following aggressive, high-dose conformal radiotherapy is common but rarely severe. Dosimetric variables addressing the longitudinal and circumferential character of the esophagus have biologic rationale and are predictive of late toxicity. Further studies are needed to assess whether these parameters are better predictors than those derived from traditional DVHs.

Acute Disease↗

PubMed1999

Fractionated external-beam radiation therapy for meningiomas of the cavernous sinus.

PURPOSE: Despite advances in microsurgical technique, many cavernous sinus meningiomas remain unresectable or only partially resectable, prompting referral of patients for radiation therapy. Stereotactic radiosurgery is recommended as therapy at some institutions. We evaluated our experience with fractionated radiotherapy to permit comparison with single-fraction radiosurgery. MATERIALS AND METHODS: Between July 1985 and January 1998, 21 women and 7 men were treated for primary (21) or recurrent (7) cavernous sinus meningiomas. Of these, 22 tumors were subtotally resected and 6 were unresectable. Of the 28 lesions, 26 were categorized histologically as benign (16), aggressive-benign (7), or malignant (3); 2 were not biopsied. All patients were treated with fractionated photon irradiation to a median dose of 53.1 Gy. We assessed prognostic factors for overall (OS) and progression-free survival (PFS), including age, gender, presentation (primary vs. recurrent), extent of surgical resection, radiotherapy dose, and technique. Influence of radiotherapy dose and technique on acute and late treatment toxicities was analyzed. RESULTS: One patient died of disease and 2 others were alive with progressive disease at last follow-up, yielding 8-year actuarial OS and PFS of 96% and 81%, respectively. Univariate analysis showed that none of the prognostic factors tested was significantly associated with OS or PFS. There were two late side effects of treatment: an orbital sac fibrosis and a 6-month decline of cognitive function documented by formal neuropsychiatric testing. Neither radiotherapy dose nor technique significantly influenced late toxicity. CONCLUSION: For unresectable or subtotally resected cavernous sinus meningiomas, fractionated radiotherapy provides patients with excellent progression-free survival and minimal treatment-related toxicity.

Adolescent↗

PubMed1980

Effect of deflector shields fitted in the milking machine teatcup liner on bovine udder disease.

Deflector shields were inserted in the teatcup to prevent 'impacts' against the teat end, and their effect on the rate of new udder infections was studied on 15 commercial dairy farms in Britain and 16 in Australia. Small metal shields were fitted between the liner barrel and short milk tube of 2 teatcups in each cluster in a milking installation so that all cows in a herd always had the same 2 quarters shielded. Half-udder comparisons were made using 1039 cows in the British herds and 1268 in the Australian herds. Herds were quarter-sampled for cytological and bacteriological examination when shields were fitted at the start of the experiment and again after 6 months. The shield effects were similar in the 2 experiments. The combined results from the 31 farms showed that 10.5% fewer quarters became infected when protected by shields (P less than 0.05). In the 1287 cows that had no infected quarters at the start of the trial, 15% fewer quarters became infected when protected by shields (P less than 0.01). The shield effect was mainly confined to hind quarters in which 23% fewer shielded quarters became infected (P less than 0.001). The small reduction of 2% in forequarters was not significant. In the 16 herds in which post-milking disinfection of teats was practised, shielded quarters had 23.5% fewer new infections than unshielded quarters (P less than 0.01). In 6 British herds milked in installations classed as non-standard, shielded quarters had almost 50% fewer new infections than the unshielded quarters (0.05 less than P less than 0.10). The results provide evidence of a milking machine effect, at varying levels of intensity, to increase new infection rates on all or most farms. Control of this machine effect could lead to substantial reduction in new infections in some herds and a modest reduction in most.

Animals↗

PubMed1980

The incidence of headache following various techniques of metrizamide myelography.

The relationship between various technical factors and the incidence of side effects, particularly headache, following metrizamide myelography has been investigated in 203 patients. The higher incidence of side-effects which has been demonstrated in females was of statistical significance, whilst the higher incidence which followed cervical myelography via lateral C1-2 puncture was not. None of the other parameters considered (needle size, weight of iodine injected, or patient's age) had any influence. The greater frequency of side-effects in women cannot be readily explained, though it may reflect the higher incidence of headaches which is said to occur in females following diagnostic lumbar puncture. The results of this study suggest that metrizamide is no more likely to produce headache than other myelographic contrast agents, or indeed, diagnostic lumbar puncture.

Adult↗

PubMedDate not supplied

A phase II trial testing the thermal dose parameter CEM43 degrees T90 as a predictor of response in soft tissue sarcomas treated with pre-operative thermoradiotherapy.

We prospectively evaluated whether delivering a thermal dose of > 10 cumulative equivalent minutes at 43 degrees C to >90% of the tumour sites monitored (CEM43 degrees T90) would produce a pathologic complete response (pCR) in > 75% of high-grade soft tissue sarcomas treated pre-operatively with thermoradiotherapy. The impact of thermal dose on local failure (LF), distant metastasis (DM), and toxicity was also assessed. Thirty-five patients > or = 18 years old with grade 2 or 3 soft tissue sarcomas accessible for invasive thermometry were enrolled on the protocol. All patients received megavoltage external beam radiotherapy (RT) in daily fractions of 1.8-2.0 Gy, five times a week, to a median total dose of 50 Gy and an initial hyperthermia treatment (HT) of I h duration utilizing the BSD 2000 with Sigma 60 or MAPA applicators at frequencies of 60-140 MHz. Further HT was given for patients with CEM43 degrees T90 > 0.5 after initial HT ('heatable' patients), twice a week to a maximum of 10 HT or CEM43 degrees T90 > 100. Of the 35 patients entered, 30 had heatable tumours, one of which was inevaluable for pCR or LF as the patient died of DM prior to surgery, leaving 29 evaluable patients. Of these 29 patients, 15 (52%) had a pCR (95% CI: 37-73%), significantly less than the projected rate of > or = 75% (p = 0.02). Of the 25 heatable tumours that achieved CEM43 degrees T90 > or = 10, 14 (56%) had a pCR (95% CI: 39-78%) significantly less than the projected rate (p = 0.06). Three of the 29 patients (10%) with heatable tumours had a LF, versus 1/5 unheatable tumours (p = 0.48). Fourteen of the 30 patients (47%) with heatable tumours developed DM, versus 2/5 unheatable tumours (p = 1.00). Ten of the 30 patients (33%) with heatable tumours developed treatment-induced toxicity. Thus, no correlation of thermal dose with histologic response was observed. Prospective control of CEM43 degrees T90 failed to achieve the projected pCR rate following pre-operative thermoradiotherapy for high-grade soft tissue sarcomas, despite excellent local control. Possible explanations for this outcome are discussed.

Adult↗