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Biomedical subjects

R Maughan

Publications and source records attributed to R Maughan.

18 recordsLinked to original sources
PubMed1996

Conformal mixed neutron and photon irradiation in localized and locally advanced prostate cancer: preliminary estimates of the therapeutic ratio.

PURPOSE: To determine the incidence of chronic toxicity and the probability of biochemical and histologic complete response among patients with nonmetastatic prostate cancer, treated with three dimensional (3D) conformal mixed neutron and photon irradiation. METHODS AND MATERIALS: Between November 1991 and December 1994, 151 patients with prostate cancer were entered in three prospective dose-finding studies of conformal mixed neutron and photon irradiation. Patients with low stage, low to intermediate grade prostate cancer (T1-2NXM0, Gleason Score < or = 7) received 38 Photon Gy (PhGy) plus 9 (51 patients) or 10 (53 patients) Neutron Gy (NGy) to the prostate and seminal vesicles. Forty-seven patients with locally advanced prostate cancer (T3-4 N0-1 M0 and/or Gleason Score > or = 8) received 15 NGy + 18 PhGy to the prostate and seminal vesicles and 9 NGy + 18 PhGy to the pelvic lymph nodes. RESULTS: The median follow-up was 16 months (range: 3-30 months). There was no Grade 3-5 GI or GU toxicity recorded. At 20 months, the actuarial rates of Grade 2 GI morbidity were 6 and 29% for the 9-10 and 15 NGy protocols, respectively (p = 0.07). At 20 months, the incidences of Grade 2 GU morbidity were 4 and 16%, respectively (p = 0.08). Stiffness in flexing or abducting the hips was seen in 20 and 42% of patients receiving 9-10 and 15 NGy, respectively (p = 0.01). Potency was maintained in 65% of all patients. Among patients with an initial PSA < or = 10, 100% had a 12-month PSA < 2 and 78% < 1 ng/ml. Negative postradiation biopsies were seen in 30% of patients 6 months, 79% at 12 months, and 84% of patients at 18 months. CONCLUSION: The use of conformal mixed neutron and photon irradiation has been well tolerated with no severe bladder or rectal complications observed. However, because of the enhanced toxicity seen with 15 NGy, the current maximum dose levels of neutron irradiation have been limited to 11 NGy.

Adenocarcinoma↗
PubMed1996

RBE variation between fast neutron beams as a function of energy. Intercomparison involving 7 neutrontherapy facilities.

In fast neutron therapy, the relative biological effectiveness (RBE) of a given beam varies to a large extent with the neutron energy spectrum. This spectrum depends primarily on the energy of the incident particles and on the nuclear reaction used for neutron production. However, it also depends on other factors which are specific to the local facility, eg, target, collimation system, etc. Therefore direct radiobiological intercomparisons are justified. The present paper reports the results of an intercomparison performed at seven neutrontherapy centres: Orléans, France (p(34)+Be), Riyadh, Saudi Arabia (p(26)+Be), Ghent, Belgium (d(14.5)+Be), Faure, South Africa (p(66)+Be), Detroit, USA (d(48)+Be), Nice, France (p(65)+Be) and Louvain-la-Neuve, Belgium (p(65)+Be). The selected radiobiological system was intestinal crypt regeneration in mice after single fraction irradiation. The observed RBE values (ref cobalt-60 gamma-rays) were 1.79 +/- 0.10, 1.84 +/- 0.07, 2.24 +/- 0.11, 1.55 +/- 0.04, 1.51 +/- 0.03, 1.50 +/- 0.04 and 1.52 +/- 0.04, respectively. When machine availability permitted, additional factors were studied: two vs one fraction (Ghent, Louvain-la-Neuve), dose rate (Detroit), influence of depth in phantom (Faure, Detroit, Nice, Louvain-la-Neuve). In addition, at Orléans and Ghent, RBEs were also determined for LD50 at 6 days after selective abdominal irradiation and were found to be equal to the RBEs for crypt regeneration. The radiobiological intercomparisons were always combined with direct dosimetric intercomparisons and, when possible in some centres, with microdosimetric investigations.

Abdomen↗
PubMed1995

Alternating conformal neutron and photon irradiation for locally advanced adenocarcinoma of the prostate.

The substantial local failure rate for patients with locally advanced carcinoma of the prostate (LACaP) following photon irradiation, the association of local failure with a poor prognosis, and the promising results of mixed neutron/photon (40%/60%) radiotherapy supplied the rationale for this study. The purpose of this study was to evaluate the combined advantages of mixed neutron/photon (75%/25%) irradiation, 3D treatment planning, as well as fully conformal beam shaping capabilities in reducing the morbidity associated with neutron irradiation. The first 35 patients treated with this technique are the basis for this analysis. After CT stimulation and treatment planning, the normal tissue and target structures were entered into the 3D planning system. The neutron dose was delivered in 15 fractions at 1.0 Gy/fraction (NGy) to the prostate and seminal vesicles (PSV) and 0.6 NGy/fraction to the pelvic lymph nodes (LN). The photon dose was given in 10 fractions of 1.8 Gy each to both the PSV and LN volumes. Neutron and photon dose-volume histograms (DVHs) were generated in each patient for the prostate, seminal vesicles, lymph nodes, bladder, and rectum. The adequacy of the neutron and photon components of the treatment were compared with respect to target volume and normal tissue irradiation. Based on the DVH analysis, the prostate and seminal vesicles received the prescribed dose with both neutrons (99% +/- 2%) and photons (99% +/- 2%). There was no significant difference in the dose to the bladder and rectum for both the neutrons and photons. The acute treatment related reactions have been mild, with only one grade III bladder reaction. The 3D conformal technology utilized in this study has been shown to allow for the delivery of neutron irradiation with no increase in dose to the adjacent normal tissues compared with that achieved with conformal photon treatment. Further follow-up will reveal whether the dosimetric advantage demonstrated by this technique translates into an improved therapeutic ratio.

Adenocarcinoma↗
PubMed1992

Pericardiotomy improves left ventricular compliance during sepsis-induced pulmonary artery hypertension.

Sepsis-induced pulmonary artery hypertension (SIPAH) causes an increase in right ventricular (RV) afterload, dilatation of the RV, leftward shift of the interventricular septum (IVS), and therefore decreases left ventricular compliance (LVC). This study was designed to evaluate the role of pericardiotomy during SIPAH as an alternative to vasodilators (which cause a detrimental increase in shunt fraction) to improve LVC. Systemic and pulmonary hemodynamics, pulmonary function, RV, and LVC were acquired at baseline (BL), during SIPAH with closed pericardium (PAHCP) and after opening the pericardium (PAHOP). Systemic hemodynamics and pulmonary function did not change significantly during the experiment. The infusion of live bacteria induced a significant rise in mean pulmonary artery pressure from 16 +/- 5.3 at BL to 36.8 +/- 3.3 and 35.0 +/- 6.4 mm Hg during PAHCP and PAHOP, respectively, (P less than 0.05). Pulmonary vascular resistance index and right ventricular stroke work index (RVSWI) displayed a similar rise in response to SIPAH (P less than 0.05 vs BL). Pericardiotomy did not affect pulmonary hemodynamics or RVSWI. Right ventricular contractility did not increase following pulmonary hypertension while the pericardium was closed (440 +/- 78 vs 410 +/- 125, P less than 0.05); however, it rose, although not significantly, to 615 +/- 326 after pericardiotomy. RV time tension index displayed a rise during SIPAH with the pericardium intact and returned to baseline values after pericardiotomy; however, these changes were not significant. RVC did not change significantly throughout the experiment. In contrast, LVC decreased significantly after SIPAH and significantly improved after pericardiotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Plasminogen activator in normal subjects after exercise and venous occlusion: t-PA circulates as complexes with C1-inhibitor and PAI-1.

Exercise to exhaustion was associated with the appearance in plasma of plasminogen activator (PA) in several mol wt forms, as identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with zymography. A number of active bands, all immunologically identified as tissue-type PA (t-PA), were observed. The major form had an apparent mol wt of approximately 60,000 and is due to free t-PA. The other strong bands had apparent mol wts of approximately 110,000 and 180,000. The 110,000 band, also present in pre-exercise samples, represents t-PA complexed with its major inhibitor (PAI-1), and the 180,000 band is due to t-PA complexed with C1 inhibitor. The released forms of t-PA were cleared rapidly after cessation of exercise at exhaustion. Urokinase-type PA (u-PA) activity was also identified in pre- and postexercise samples at an apparent mol wt of approximately 50,000. This is consistent with its being free u-PA; no complexed forms of u-PA were observed. Qualitatively similar changes in plasma PA were observed after venous occlusion. Small quantities of plasmin were generated after strenuous exercise, as observed by detection of plasmin-alpha 2-antiplasmin complex by two-dimensional immunoelectrophoresis in three of five subjects. This complex was cleared rapidly after cessation of exercise. Plasmin-alpha 2-antiplasmin complex was not detected in any of the subjects after venous occlusion.

Fibrinolysin↗
PubMed1986

The RBE for mouse bladders after irradiation with 1 to 8 fractions of d(4)+ Be neutrons.

Mouse bladders were irradiated with 1,2,4 or 8 fractions of electrons or neutrons. Urination frequency was scored from 9 to 14 months after irradiation and this was used as a measure of the extent of bladder damage. The RBE for neutrons relative to 1.8 MeV electrons increased from 3.2 for large single doses to 5.4 for 8 fractions. Repair of sublethal injury after electron irradiation was considerable, with 63-72% of each fractionated dose repaired. Repair after neutron irradiation was less, with only 35-43% of each fractionated dose recovered. Linear-quadratic analysis of all the fractionated bladder data yielded an alpha/beta ratio for electrons of 6-7 Gy and, surprisingly, the alpha/beta ratio for neutrons was only slightly higher at about 8 Gy.

Animals↗
PubMed1984

The RBE for renal damage after irradiation with 3 MeV neutrons.

Mouse kidneys were locally irradiated with single doses or up to 8 fractions of 240 kV X rays or 3 MeV neutrons. Damage was assessed from measurements of urine output, isotope clearance or haematocrit levels. All three assays gave steep dose-response curves by 4-5 months after irradiation. The repair capacity of the kidney was considerable after X-irradiation but was very small after irradiation with neutrons. Thus the RBE increased sharply with increasing fractionation. After large doses, an RBE of 2.3-2.5 was measured, rising to 4.5-5.1 after 8 fractions of 4 to 5 Gy X rays. Linear-quadratic analysis of these data has allowed RBE's to be calculated outside the measured dose range. The limiting RBE predicted at very low doses per fraction is 20 to 26, whereas at extremely high doses it would be as low as 1.2 to 1.4. This indicates that high RBE values may be seen in a slow turnover tissue after low doses per fraction (within the clinically relevant range) although this may not be evident after larger doses. Such high RBE's arise because of the shape of the underlying X-ray dose-response curve rather than the shape of the neutron curve.

Animals↗
PubMedDate not supplied

Growth response to enteral feeding by children with cerebral palsy.

This study evaluated the growth of 51 children with cerebral palsy after the initiation of enteral tube feedings. The children were divided into three groups according to how soon after their central nervous system (CNS) insult they were started on enteral feedings. Group 1 consisted of 14 children who were within a year of their CNS insult; they were underweight for age, but had normal length as well as weight for length. Within 6 months of initiating enteral tube feedings, most children in this group had normalized their weights. Group 2 consisted of 27 children who were within 8 years of their CNS insult; they were stunted and were underweight for both their age and their length. Within 6 months of initiating enteral feeds, the group increased both weight and weight for length to near normal, but their gains in length reached a plateau at 90% of ideal for age. Group 3 consisted of 10 children who were more than 8 years after their CNS insult. This group was severely malnourished but had some improvement in their weight for age and for length but, length for age showed no significant change. We conclude that the earlier adequate nutritional management of children with severe cerebral palsy is initiated, the more readily the nutritional deficits will reverse.

Adolescent↗