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Biomedical subjects

M Duclos

Publications and source records attributed to M Duclos.

At least 19 recordsLinked to original sources

Decreased pituitary sensitivity to glucocorticoids in endurance-trained men.

OBJECTIVE: Muscular exercise induces hypothalamo-pituitary-adrenal (HPA) axis activation and when regularly repeated, as in endurance training, leads to HPA axis adaptation. To assess whether non-professional endurance-trained (ET) men with a substantial training load and no clinical or biological features of HPA axis overactivity can present subtle alterations of HPA axis sensitivity to glucocorticoid negative feedback, nine ET men were subjected to HPA axis testing using the dexamethasone-corticotrophin-releasing hormone (CRH) test. DESIGN: Nine endurance-trained men and eight healthy age-matched sedentary men were studied. Morning plasma cortisol and 24 h urinary free cortisol (UFC) were determined and a low dose dexamethasone suppression test (LDDST) was performed followed by CRH stimulation (dexamethasone-CRH test). RESULTS: After a day without physical exercise, at 0800 h, plasma ACTH and cortisol concentrations, and the 24 h UFC and UFC/urinary creatinine (UC) ratio were similar in ET and sedentary men. By contrast, clear differences between the groups were seen in cortisol and ACTH responses to the dexamethasone-CRH test. In eight ET subjects, after LDDST, basal ACTH and cortisol levels were similar to those of sedentary men, whereas one ET subject displayed a poor suppression of cortisol level (131 nmol/l). After injection of CRH, however, three of nine ET men's cortisol levels were not suppressed by dexamethasone but instead displayed significant CRH-induced increase (peak cortisol: 88, 125 and 362 nmol/l). No sedentary subject exhibited any increase in cortisol levels. CONCLUSION: Three of nine ET men with a mean maximum rate of O2 uptake (VO2, max) of 61 ml/kg per min, running 50-70 km per week, were resistant to glucocorticoid suppression during the combined dexamethasone-CRH test.

Adult↗

[Effects of physical training on endocrine functions].

Muscular exercise has an impact on endocrine functions. A single bout of exercise (for example, running for 30 minutes) activates certain endocrine systems required to maintain body homeostasis. Moreover, the effects of exercise persist after the end of exercise, continuing during the recovery period. Training, i.e. regularly repeated exercise, can affect endocrine functions by modifying hormonal responses to exercise and/or by modifying endocrine functions in resting conditions. In other words, endocrine functions adapt to repeated muscular exercise. The understanding of such modifications should allow avoiding unwarranted hormonal substitution in sportsmen and sportswomen.

Adrenocorticotropic Hormone↗

Hippocampal and striatal [(3)H]5-HT reuptake under acute stressors in two rat strains differing for their emotivity.

Spontaneously hypertensive rats and Lewis rats differ in their anxiety levels and in their serotonergic and corticotropic responses to stress. Since the 5-HT transporter plays a key role in 5-HT neurotransmission, we have analyzed whether hippocampal and/or striatal [(3)H]5-HT reuptake kinetics are altered by stress in a strain-dependent manner. It was found that forced swimming, treadmill running, or restraint for 30 min affected neither hippocampal nor striatal [(3)H]5-HT reuptake K(m) and V(max) values in the two rat strains. This study, which is the first to examine the impact of acute stress on [(3)H]5-HT reuptake with respect to the nature of the stressor, the brain region analyzed, and the rat strain, could reinforce the hypothesis that extracellular 5-HT levels during stress are representative of 5-HT release.

Animals↗

Corticotropic and serotonergic responses to acute stress with/without prior exercise training in different rat strains.

The ability to cope with exercise training depends both on environmental and genetic background; however, whether the genetic status may affect (i) the hormonal status of trained subjects and, (ii) its responses to a heterotypic stressor is unknown. Herein, we have used Spontaneously Hypertensive Rats (SHR) and Lewis rats, that differ with regard to their psychoneuroendocrine profiles, to study the influences of an 8-week training programme and/or a 1-h immobilization stress on plasma adrenocorticotropin (ACTH) and corticosterone levels. In addition, brain serotonin metabolism was also measured as an index of neurochemical reactivity to stress. The amplitude of immobilization-elicited increases in ACTH levels which differed with the rat strain (Lewis > SHR), was amplified by prior training; besides, training decreased the strain difference in basal corticosterone (SHR > Lewis) and affected corticosterone response to immobilization in a strain-dependent manner. Thus, immobilization, which increased corticosterone levels in sedentary Lewis but not in SHRs, did not reveal interstrain differences in trained rats. Taken with the observation of a stimulatory effect of training on adrenal weights in SHRs, but not in Lewis, it is concluded that the effects of training on the corticotropic axis depend on the genetic profile of the individual. Lastly, training amplified the response of midbrain (but not striatum or hippocampus) serotonin metabolism to immobilization in a strain-independent manner although the levels of serotonin precursor, namely tryptophan, varied with training and immobilization in a strain-dependent manner. This study shows that some neuroendocrine and neurochemical effects of training undergo interindividual variability.

Adrenal Glands↗

Abdominal obesity increases overnight cortisol excretion.

Although plasma and 24 h urinary free cortisol (UFC) levels are normal in obese subjects, pharmacological investigations have identified minor hypothalamo-pituitary-adrenal axis differences in patients with abdominal body fat distribution (A-BFD) vs peripheral BFD (P-BFD). Using recent tools such as saliva cortisol or overnight urinary free cortisol upon creatinine ratio (UFC/UC) determinations, we have investigated a population of obese females according to their body fat distribution. In-patients subjects (no.=82) were subjected to routine biochemical testing, 24 h and overnight UFC/UC, basal and post-1 mg overnight dexamethasone-suppressing test plasma and saliva cortisol determinations. Central obesity defined by a waist-to-hip ratio (WHR) >0.85 was found in 64% of the subjects vs 87% when defined by waist girth (WG) corrected for age. Despite identical body mass index, A-BFD subjects were more prone to hypertension using both classifications and had higher triglycerides (WHR classification) or higher triglycerides, cholesterol and glycemia (WG classification). Plasma cortisol levels were similar but saliva cortisol levels were lower in the A-BFD group using the WG classification. The 24 h UFC/UC were similar but the overnight UFC/UC were higher in the A-BFD group using the WHR classification. These mild differences in cortisol nocturnal secretion and free cortisol indexes in subjects with different body fat mass distribution suggest that their hypothalamo-pituitary-adrenal axis has a spontaneously subtly different regulation.

Abdomen↗

Rapid leptin decrease in immediate post-exercise recovery.

OBJECTIVE: Leptin concentrations in humans are known to decrease in response to fasting. The aim of this work was to investigate whether leptin levels might also be modified by exercise-induced negative energy balance. SUBJECTS: Eight male runners reported in the morning from 0800 to 1200 h for (i) one resting session (sitting) and (ii) one exercise-and-rest session (2 h run and 2 h rest). MEASUREMENTS: Plasma leptin, free fatty acids (FFA), glycerol, cortisol and salivary cortisol were assayed in both sessions at 1200 h. RESULTS: After exercise-and-rest the leptin concentrations were lower than after rest (1.7 +/- 0.1 vs 2.5 +/- 0.2 micrograms/l, P < 0.05), i.e. a mean decrease of 30.3 +/- 4.5% (range 9.5-45.8). Plasma FFA, glycerol and cortisol concentrations increased: FFA 0.78 +/- 0.08 vs 0.18 +/- 0.04 mmol/l, glycerol 0.13 +/- 0.01 vs 0.04 +/- 0.01 mmol/l, and cortisol 428 +/- 36 vs 279 +/- 27 nmol/l. A negative correlation was found between plasma FFA and leptin levels (r = -0.5, P < 0.05) and between plasma glycerol and leptin levels (r = -0.05, P < 0.05). No correlation was found between leptin and cortisol levels. CONCLUSIONS: In normal subjects with low body fat, a strenuous exercise-and-rest lowers leptin levels by a mean of 30%. A role of lipolysis possibly via increased plasma free fatty acids and glycerol levels is suggested. Cortisol does not seem to be involved.

Adult↗

The dexamethasone-suppressed corticotrophin-releasing hormone stimulation test in anorexia nervosa.

OBJECTIVE: The dexamethasone-CRH test (combination of dexamethasone-induced suppression of HPA axis function and subsequent stimulation with oCRH) (Dex-CRH test) has been proposed to fully distinguish ACTH-dependent Cushing's disease (CD) from pseudo-Cushing's states (PCS), i.e. tumoural vs. functional hypercortisolism. A plasma cortisol concentration greater than 38 nmol/l 15 min after CRH injection has been demonstrated to identify all cases of CD and to exclude all cases of PCS. Although obviously not a PCS from a clinical point of view, anorexia nervosa (AN) is associated with CRH-driven hyperactivity of the HPA axis. This study reports the response of AN patients, a model of functional biological hypercortisolism, to the Dex-CRH test. PATIENTS AND METHODS: Nineteen women affected with anorexia nervosa and 6 healthy sex-matched controls were studied. RESULTS: Three of 19 AN patients had an abnormal 24-h urinary free cortisol excretion (UFC), whereas 1 of 19 AN had increased overnight UFC. AN subjects had inadequately suppressed plasma cortisol after low-dose dexamethasone suppression test (LDDST) (cortisol 192.8 +/- 63.4 vs. < 27 nmol/l, AN vs. controls, respectively). Seven of 19 AN patients had plasma cortisol levels above 50 nmol/l after LDDST. None of the AN patients had CRH-induced increases in plasma ACTH or cortisol (basal cortisol 192. 8 +/- 63.4 and peak cortisol 181.7 +/- 59.9 nmol/l). Despite unresponsivenessto CRH and because of the lack of suppression after dexamethasone, using the single plasma cortisol threshold value of 38 nmol/l obtained at 15 min during the Dex-CRH test would have been misclassified in half of our AN population (9 of 19). CONCLUSION: Since anorexia nervosa represents a model of functional hypercortisolism that shares similar pathophysiological mechanisms to the other causes of pseudo-Cushing's states, we suggest testing all causes of pseudo-Cushing's states using the dexamethasone-CRH approach to (i) describe the actual responses of clinically relevant pseudo-Cushing's states and (ii) to improve our knowledge of the pathophysiological discrepancies between the various causes of pseudo-Cushing's states. Lastly, the evaluation of dexamethasone metabolism (absorption, volume of distribution, clearance) may help to gain more insight into the diagnostic value of the dexamethasone-CRH test.

Adrenocorticotropic Hormone↗

Reversibility of endurance training-induced changes on glucocorticoid sensitivity of monocytes by an acute exercise.

OBJECTIVE: The aim of this study was to address the effect of endurance training on monocyte glucocorticoid sensitivity in vitro. METHODS: For this purpose, in vitro dexamethasone inhibition of lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) secretion in cultures of peripheral monocytes was compared in 6 untrained subjects (UT) and in 6 endurance-trained (ET) men at 0800 h, 24 h after the end of the last session of exercise (ET men). Moreover, to test the plasticity of these monocytes glucocorticoid sensitivity in ET men, the effect of an acute bout of exercise was further studied 2 h after the end of a 2-h run at 65-75% VO2max (1200 h) and compared to the results of UT after 4 h of rest. RESULTS: At 0800 h, monocytes from ET were more sensitive to LPS: lower LPS concentration in ET compared to UT men (0.003 vs. 0.03 microg/ml) induced similar IL-6 concentrations in both ET and UT men (168.4 +/- 29.9 pg/ml with 0.003 microg/ml LPS vs. 160.1 +/- 34.4 pg/ml with 0. 03 microg/ml LPS, ET vs. UT, respectively, P > 0.05 for IL-6). No effect of sampling time was observed in UT subjects (0800 h vs. 1200 h). This was not the case for ET as at 1200 h, compared to pre-exercise values, the LPS-induced IL-6 production was not significantly different from that obtained in UT. Moreover, when sensitivity to dexamethasone (Dex) was studied and expressed as the percent inhibition of stimulated IL-6 production with 0.3 microg/ml LPS, at 0800 h the percent inhibition was lower in ET subjects compared to UT (P < 0.01 ET vs. UT men) for each Dex concentration used [10-11-10-8 M]. After exercise, the inhibitory effect of Dex on LPS-induced IL-6 production was restored in ET and was no longer significantly different from that obtained in UT. CONCLUSION: We demonstrate in vitro plasticity of monocyte glucocorticoid sensitivity of endurance trained men, with training-induced decreased glucocorticoid sensitivity and acute exercise-induced return to the levels of the control untrained men.

Adult↗

Distribution of lung density after strenuous, prolonged exercise.

The postexercise alteration in pulmonary gas exchange in high-aerobically trained subjects depends on both the intensity and the duration of exercise (G. Manier, J. Moinard, and H. Stoïcheff. J. Appl. Physiol. 75: 2580-2585, 1993; G. Manier, J. Moinard, P. Techoueyres, N. Varène, and H. Guénard. Respir. Physiol. 83: 143-154, 1991). In a recent study that used lung computerized tomography (CT), evidence was found for accumulation of water within the lungs after exercise (C. Caillaud, O. Serre-Cousine, F. Anselme, X. Capdevilla, and C. Prefaut. J. Appl. Physiol. 79: 1226-1232, 1995). On representative slices of the lungs, mean lung density increased by 0.040 +/- 0.007 g/cm(3) (19%, P < 0.001) in athletes after a triathlon. To verify and quantify the mechanism, we determined the change in pulmonary density and mass after strenuous and prolonged exercise using another exercise protocol and methodology for CT scanning. Nine trained runners (age 30-46 yr) volunteered to participate in the study. Each subject ran for 2 h on a treadmill at a rate corresponding to 75% of maximum O(2) consumption. CT measurements were made before and immediately after the exercise test with the subject supine and holding his breath at a point close to functional residual capacity. The lungs were scanned from the apex to the diaphragm and reconstructed in 8-mm-thick slices. Attenuation values of X-rays in each part of the lung were expressed in Hounsfield units (HU), which are related to density (D): D = 1 + HU/1,000. No significant alteration in pulmonary density (0.37 +/- 0.04 vs. 0.35 +/- 0.03, not significant) was observed after the 2-h run test. Although lung volume slightly increased (change of 166 +/- 205 ml, P < 0.05), lung mass remained stable because of a change in density distribution. We failed to detect any changes in postexercise lung mass, suggesting that other mechanisms need to be considered to explain the observed alterations in pulmonary gas exchange after prolonged strenuous exercise.

Adult↗

Corticotroph axis sensitivity after exercise in endurance-trained athletes.

OBJECTIVE: The present study was conducted in order to describe human hypothalamo-pituitary adrenal (HPA) axis adaptation in a model of repeated physical stress (endurance training) that causes a moderate increase in cortisol levels. SUBJECTS: We performed the same stimulation tests (adrenal stimulation with ACTH or pituitary stimulation with combined CRH/LVP) in a population of 8 endurance-trained athletes in two distinct situations: resting (baseline cortisol values) and 2 h after the end of strenuous exercise (increased cortisol values) to evaluate the HPA axis sensitivity to endogenous sustained increases in cortisol concentrations. MEASUREMENTS: During these tests, saliva and plasma cortisol (Fs and Fp, respectively) were assessed and compared. RESULT: Cortisol values in both plasma and saliva at the end of 2 h of exercise were significantly higher than in rested controls: Fs 11.5 +/- 1.3 vs 6.5 +/- 0.8 nmol.l-1 and Fp 428 +/- 36 vs 279 +/- 27 nmol.l-1 (post exercise vs post rest sessions, respectively, P < 0.001 for both). After either hormone test (CRH/LVP or ACTH), cortisol levels in plasma and saliva increased similarly when rest was compared to post exercise. Saliva variations (delta %) under exogenous hormone stimulation were dramatically greater than plasma variations. For example, under ACTH stimulation, the relative increments in cortisol were on control day: delta Fs 980 +/- 139 vs delta Fp 218 +/- 43% (saliva vs plasma, respectively, P < 0.05) and on exercise day: delta Fs 605 +/- 89 vs delta Fp 102 +/- 14% (saliva vs plasma, respectively, P < 0.05). CONCLUSIONS: In endurance-trained athletes, displaying a moderate but sustained endogenous cortisol increase: (1) ACTH responses following pituitary stimulation are not blunted, (2) cortisol responses following maximal adrenal stimulation are not blunted. Our results favour the hypothesis of a decreased pituitary sensitivity to cortisol negative feedback whereas the hypothesis of a major decreased adrenal sensitivity to ACTH was discarded. The greater ability of saliva assays to detect a cortisol increase strongly supports its use in the study of HPA physiology, whether under basal or dynamic conditions.

Adrenocorticotropic Hormone↗

Overnight urinary free cortisol determination: a screening test for the diagnosis of Cushing's syndrome.

OBJECTIVE: The collection of urine over 24 h to measure free cortisol (UFC) is used to diagnose Cushing's syndrome. However, a complete collection of urine is not easy to achieve and the sampling is frequently inaccurate, so a 24 h collection for the determination of UFC excretion is used as a confirmatory rather than a screening test for Cushing's syndrome. Our objective was to evaluate a more convenient urine collection for screening patients suspected of Cushing's syndrome. DESIGN: We have studied the possibility of using night-time (from 2000 h to 0800 h) UFC excretion as a screening test for Cushing's syndrome ('overnight UFC'). PATIENTS: Thirty patients with proven Cushing's syndrome were studied before treatment (21 cases of Cushing's disease, two cases of ectopic ACTH secretion, seven of adrenal adenoma). The results were compared to those from 150 control obese subjects. MEASUREMENTS: Overnight UFC, and creatininuria (UC), were evaluated at least once in the patients and in all subjects. The 24 h-UFC and UC were determined at least once in the patients and in 56 control subjects. RESULTS: The overnight UFC/UC ratio clearly separated all but one patient of the two groups: 194 +/- 386 vs 5.7 +/- 3.4 nmol/mumol (P < 0.0005) (ranges 16.2-2024 vs 0.6-17.4, Cushing's syndrome vs controls, respectively). The only patient with Cushing's syndrome who had an overnight UFC/UC ratio that overlapped with that of controls suffered from renal failure. The 24 h UFC/UC ratio of the patients differed from the ratio of controls: 184 +/- 365 vs 8.4 +/- 4.1 nmol/mumol (P < 0.0005) (ranges 14-1639 vs 1.5-21.2, respectively). Four patients with Cushing's syndrome had 24 h UFC/UC ratios lower than the upper control ratio. CONCLUSION: The overnight urinary sampling is a simple procedure compared to the 24 h urine collection performed in out-patients. For a sensitivity set at 100%, the specificities were 97% for the overnight UFC/UC ratio and 87% for the 24 h-UFC/UC ratio. This therefore appears to provide a good screening method for Cushing's syndrome.

Adult↗

Enhancement of prostate tumor volume definition with intravesical contrast: a three-dimensional dosimetric evaluation.

PURPOSE: To assess the impact of intravesical contrast during computed tomography (CT) simulation on prostate tumor volume definition and dose distribution. METHODS AND MATERIALS: Sixteen patients with localized adenocarcinoma of the prostate underwent CT-based virtual simulation in preparation for definitive radiotherapy. Patients were immobilized with a foam cradle and an initial CT was performed after oral but without intravesical contrast (noncontrast scan). A second scan was performed following administration of intravesical contrast (contrast scan). Beam apertures were designed on the noncontrast scans and digitized into the contrast scan file. Beam apertures were also designed on the contrast scans. Isodose plans were generated for several beam apertures and arrangements. RESULTS: There was enhanced visualization of the prostate at the cephalad portion of the field for 15 of the 16 cases. The mean differences between the noncontrast and contrast volumes was significant (p = 0.0001). The mean percent underdosage to the prostate ranged from 3.9% to 18.6%, depending upon the target volume and beam arrangement. CONCLUSION: This study demonstrates the necessity of using intravesical contrast for defining the location of the prostate during CT simulation. The underestimation of the extent of the prostate when omitting intravesical contrast leads to significant underdosage. The value of intravesical contrast is most evident when small (prostate only) conformal fields are used.

Adenocarcinoma↗

Trained versus untrained men: different immediate post-exercise responses of pituitary adrenal axis. A preliminary study.

The hypothalamo-pituitary-adrenal axis is involved throughout the exercise-recovery cycle. Nevertheless, differences in hormone responses during early recovery between sedentary and endurance trained subjects are not well known. The aim of this preliminary study was to monitor plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations both during and after the end of running exercise performed by four endurance trained adults (marathon men) compared to four sedentary subjects. Two parameters, i.e. intensity and duration, were changed on 4 consecutive days. The 1st day (D0) was spent in the laboratory: all blood samples were obtained at rest to determine diurnal variations of each hormone. On the following days (D1-D4) the subjects exercised: D1 and D2 brief (20 min), light (50% maximal heart rate HRmax, D1) or strenuous (80% HRmax, D2), D3 and D4 prolonged (120 min), light (D3) or strenuous (D4). In both groups, neither brief (D1, D2) nor prolonged light exercise (D3) induced any significant variation in plasma ACTH or cortisol concentrations. Plasma ACTH and cortisol concentrations increased only if the exercise was intense and prolonged (D4). The training factor did not modify the intensity or duration thresholds for the activation of the pituitary-adrenocortical response to exercise in the conditions of our experiment. However, during immediate recovery from the four exercise regimens, the plasma ACTH concentrations of the marathon men were constantly above the values of the sedentary subjects, although plasma cortisol concentration remained similar in both groups. As an indirect means of evaluating the relationships between ACTH and cortisol we compared the areas under the cortisol and ACTH curves (AUC) from 0.5 to 3.5 h during recovery from D1 to D4 compared to D0 at the same time. Cortisol AUC were similar in the sedentary subjects and marathon men although the ACTH AUC were different in the sedentary subjects and marathon men, suggesting a change in the pituitary-adrenal relationship at some yet indeterminate level. During the immediate recovery from exercise whatever its intensity, the magnitude of the ACTH response was increased in the trained subjects but with a reduced effect upon its target, the adrenal glands. This phenomenon has not been described in the literature. Two non-exclusive phenomena may be involved, i.e. a decreased adrenal sensitivity to ACTH stimulation, and/or a decreased hypothalamo-pituitary axis sensitivity to cortisol negative feedback.

Adrenal Glands↗

Differences in dosimetry and toxicity between definitive and postprostatectomy radiation therapy.

PURPOSE: To compare the volumes of normal tissue irradiation and toxicity in patients treated with definitive radiation therapy or postprostatectomy radiation therapy. MATERIALS AND METHODS: Results were analyzed prospectively in 49 patients who underwent definitive or postprostatectomy radiation therapy after three-dimensional conformal treatment planning. Dose-volume histograms and the effective area irradiated were analyzed. Patient charts were reviewed and scored for acute and chronic toxicity. The mean bladder volume was 200 mL in the definitive group and 226 mL in the postprostatectomy group. The mean rectal volume was 87 mL in the definitive group and 81 mL in the postprostatectomy group. RESULTS: The dose to 25% of the rectal volume was 91% and 86% in the definitive and postprostatectomy groups, respectively. The dose to 25% of the bladder volume was 89% in the definitive group and 82% in the postprostatectomy group. The incidence of acute and chronic gastrointestinal and chronic genitourinary toxicity was similar in both groups, but acute genitourinary toxicity in the postprostatectomy group was significantly lower (P = .026). The volume of normal tissue irradiated was similar in both groups. Also, similar doses were delivered to the normal tissue. CONCLUSION: Differences in acute genitourinary toxicity are most likely secondary to radiation-induced prostatitis. Postprostatectomy radiation therapy is safe and is not associated with increased toxicity.

Acute Disease↗

Potency following conformal neutron/photon irradiation for localized prostate cancer.

PURPOSE: To assess the effect of conformal neutron/photon irradiation with or without neoadjuvant hormonal therapy on posttreatment potency. MATERIALS AND METHODS: Seventy-six patients with localized adenocarcinoma of the prostate, State T1 or T2 N0 M0, Gleason score < or = 7, were enrolled on a prospective Phase II study. Each patient received 9-10 Neutron + 38 Photon Gy. Twenty-eight patients received neoadjuvant hormonal therapy in conjunction with radiation therapy. Potency was assessed prior to starting treatment and was assessed at each subsequent follow-up visit. RESULTS: Fifty-two of patients (70%) were potent at the start of therapy. Thirty-eight of 52 (73%) had functional erections and 14 of 52 (27%) had erections termed nonfunctional, which were of insufficient strength for intercourse. After treatment, 35 of 52 (67%) retained potency. Twenty-nine of 38 (76%) with functional erections pretreatment maintained this ability. Only 6 of 14 patients (43%) with nonfunctional erection pretreatment maintained their level of potency. Neoadjuvant hormonal therapy did not impact on the ability to maintain erections. Sixty-five percent of those patients receiving hormones retained erectile function, while 69% of those who did not receive hormones maintained erectile function. Age was not a significant factor in posttreatment potency, although a trend towards potency in younger patients was observed. (p = 0.74). CONCLUSION: The majority (67%) of patients maintained their level of erectile function following conformal sequential neutron photon irradiation. This is comparable to that achieved with photon irradiation alone. No significant change in potency was seen with neoadjuvant hormonal therapy or with increasing patient age.

Adenocarcinoma↗

Hip stiffness following mixed conformal neutron and photon radiotherapy: a dose-volume relationship.

PURPOSE: To determine the relationship between dose, volume, and the incidence of hip stiffness in patients who received conformal neutron irradiation for prostate cancer. METHODS AND MATERIALS: A series of dose-searching studies using neutron irradiation for prostate cancer were performed to determine the optimal dose, fraction size, field size, technique, and proportions of photon and neutron dose. Neutron doses ranged from 9 to 20 Gy and photon doses ranged from 0 to 38 Gy. Data were analyzed by using a hip stiffness grading scale. RESULTS: Hip stiffness was recorded on follow-up examination in 30% of patients (40 out of 132) treated with fast neutrons or mixtures of fast neutron and photon radiation for prostate cancer. Hip stiffness was categorized as none (Grade 0, 92 patients), mild (Grade 1, 24 patients), moderate (Grade 2, 10 patients), or severe (Grade 3, 6 patients). The incidence of hip stiffness differed significantly by dose and volume in the five dose levels studied (p < 0.001). CONCLUSIONS: By using a mixture of conformal neutron and photon irradiation and limiting the total neutron dose to less than 13 Gy, hip stiffness toxicity could be reduced to acceptable levels.

Aged↗

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↗