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Introduction: Neck and upper-back stiffness involves discomfort/ache in the trapezius muscle (TM). The pathogenesis of 'essential neck and upper-back stiffness' without obvious causes remains uncertain. In symptomatic subjects, TM hardness correlates with decreased transverse cervical artery (TCA) blood flow to the TM. Neck and upper-back stiffness could be associated with both hemodynamic and neurological factors affecting the TM. We therefore sonographically evaluated structural factors around the accessory nerve innervating the TM impacting neck and upper-back stiffness., Methods: Participants comprised 69 healthy young adults (33 men, 36 women; 21 ± 1 y) who completed questionnaires and underwent elastography to determine TM hardness as a strain ratio and pulsed Doppler sonography to determine TCA hemodynamics. Intermuscular length was measured as the distance between sternocleidomastoid and levator scapulae muscles around the accessory nerve. Relationships of intermuscular length with symptoms, TM hardness, and TCA hemodynamics were analyzed., Results: Intermuscular length was greater in symptomatic subjects (median 2.3 mm, interquartile range 1.5-3.1 mm) than in asymptomatic subjects (median 1.8 mm, interquartile range 1.5-2.3 mm; p = 0.032). Intermuscular length correlated positively with symptom severity (r = 0.43, p = 0.014) and negatively with strain ratio for the TM (r = -0.39, p = 0.025) and peak systolic velocity in the TCA (r = -0.40, p = 0.022). Intermuscular length contributed independently to the presence of symptoms (p = 0.025, odds ratio 2.26, 95% confidence interval 1.11-4.62)., Conclusion: In symptomatic subjects, symptom severity, TM hardness and TCA hemodynamics all correlated with greater intermuscular length. Structures around the accessory nerve could be associated with the pathogenesis of essential neck and upper-back stiffness., (© 2024 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Purpose: Neck and upper-back stiffness is encountered in daily life, with symptoms appearing as dullness or aches predominantly in the trapezius muscle (TM). Our previous study demonstrated that TM hardness as measured with a muscle hardness meter correlates well with transverse cervical artery (TCA) flow supplying the TM. Muscle hardness meters, however, cannot measure hardness in the TM alone. Meanwhile, recent advances in ultrasound elastography have enabled the evaluation of localized hardness in targeted tissues. The present study, therefore, aimed to clarify the relationship between TM hardness as measured by elastography and TCA hemodynamics as measured on Doppler sonography, with reference to daily symptoms of upper-back stiffness., Methods: The study population comprised 66 healthy young adults (32 males, 34 females; mean age, 21 ± 1 years). Relationships were evaluated between TM hardness as a negative correlate of strain ratio from elastography and TCA hemodynamics on Doppler sonography. Hemodynamics in the TCA were evaluated according to the frequency of neck and upper-back stiffness., Results: TM strain ratio correlated with peak systolic velocity (PSV) in the TCA (r = 0.273, p = 0.036), particularly in symptomatic subjects (r = 0.417, p = 0.022). PSV in the TCA decreased with increasing frequency of daily symptoms (p = 0.045)., Conclusion: TCA hemodynamics correlated with muscle hardness when evaluating localized TM hardness. This relationship and low PSV in the TCA were evident in symptomatic subjects. These results suggest that PSV in the TCA is associated with neck and upper-back stiffness., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Taking a short rest after lunch suppresses increases in blood flow to the digestive organs and maintains blood flow to the brain in the afternoon, possibly providing beneficial effects in preventing post-prandial drowsiness. The present study investigated sex-dependent influences on changes in hemodynamics produced by taking a short rest after lunch., Methods: Subjects comprised 20 healthy young adults (10 men, 10 women; mean age 21 ± 1 years). Doppler sonography was performed to measure blood flow in the superior mesenteric artery (SMA) and common carotid artery (CCA) before and after lunch every hour on each day, with and without a 15-min rest with eyes closed after lunch. Blood pressure and heart rate (HR) were also measured., Results: For both men and women, peak systolic velocity (PSV) in the SMA was suppressed by taking a rest. PSV in the CCA in men was increased at 0.5 h after lunch in the resting condition but was decreased in the non-resting condition (median 109%, interquartile range [IQR] 102-120% vs. median 98%, IQR 90-107%; P = 0.037). No such differences were observed in women. Although post-prandial increases in HR were observed in women, a similar increase was only found for men in the resting condition., Conclusion: An increase in CCA blood flow was observed only in men. The present study suggests that a short rest after lunch could better promote the maintenance of blood flow to the brain in men than in women., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The staging of liver fibrosis is clinically important, and a less invasive method is preferred. Quantitative susceptibility mapping (QSM) has shown a great potential in estimating liver fibrosis in addition to R2* relaxometry. However, few studies have compared QSM analysis and liver fibrosis. We aimed to evaluate the feasibility of estimating liver fibrosis by using QSM and R2*-based histogram analyses by comparing it with ultrasound-based transient elastography and the stage of histologic fibrosis., Methods: Fourteen patients with liver disease were enrolled. Data sets of multi-echo gradient echo sequence with breath-holding were acquired on a 3-Tesla scanner. QSM and R2* were reconstructed by water-fat separation method, and ROIs were analyzed for these images. Quantitative parameters with histogram features (mean, variance, skewness, kurtosis, and 1st, 10th, 50th, 90th, and 99th percentiles) were extracted. These data were compared with the elasticity measured by ultrasound transient elastography and histological stage of liver fibrosis (F0 to F4, based on the new Inuyama classification) determined by biopsy or hepatectomy. The correlation of histogram parameters with intrahepatic elasticity and histologically confirmed fibrosis stage was examined. Texture parameters were compared between subgroups divided according to fibrosis stage. Receiver operating characteristic (ROC) analysis was also performed. P < 0.05 indicated statistical significance., Results: The six histogram parameters of both QSM and R2*were significantly correlated with intrahepatic elasticity. In particular, three parameters (variance, percentiles [90th and 99th]) of QSM showed high correlation (r = 0.818-0.844), whereas R2* parameters showed a moderate correlation with elasticity. Four parameters of QSM were significantly correlated with fibrosis stage (ρ = 0.637-0.723) and differentiated F2-4 from F0-1 fibrosis and F3-4 from F0-2 fibrosis with areas under the ROC curve of > 0.8, but those of R2* did not., Conclusion: QSM may serve as a promising surrogate indicator in detecting liver fibrosis.

Purpose: Drowsiness is often experienced in the afternoon after lunch. Decreases in blood flow to the brain secondary to increases in blood flow to the digestive organs after food intake could represent an underlying cause. As various beneficial effects of short rests on mental activities have been reported, the present study investigated hemodynamics using Doppler sonography of the common carotid artery (CCA) and superior mesenteric artery (SMA) after lunch, comparing resting and non-resting cases., Methods: Subjects comprised 24 healthy young adults (10 men, 14 women; mean age 22 ± 1 years). Sonography was performed to measure blood flow before and after lunch on each day, with and without a 15-min lying rest with eyes closed after lunch in each subject., Results: The timing of the peak velocity-time integral in the SMA in resting cases was delayed to 1.5 h after lunch compared to 0.5 h in non-resting cases. Although end-diastolic velocity in the CCA decreased after lunch, this decrease was suppressed in resting cases compared to non-resting cases even 4.5 h after lunch (median 96%, interquartile range [IQR] 83-102% vs. median 87%, IQR 77-92%; P = 0.037). Mean velocity (MV) in the CCA maintained unchanged after lunch in resting cases (P = 0.318), whereas non-resting cases showed decreased MV after lunch (P < 0.001)., Conclusion: These findings suggest that a short lying rest with eyes closed suppresses increases in blood flow to the digestive organ and maintains blood flow to the brain after lunch. These hemodynamic changes might help explain the benefits of afternoon rests., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Lower leg oedema occurs physiologically in the evening after daytime activity. Various oedema-related sonographic findings have recently been reported, but this physiological oedema has not been evaluated quantitatively using imaging examinations. The present study investigated whether sonography could detect physiological lower leg oedema, comparing measured values between the morning and late afternoon. Diameters of leg veins were also measured as a possible source of leg oedema. Subjects comprised 55 healthy young women (mean age, 21 ± 1 years). Oedema-related findings such as papillary dermis thickness, subcutaneous adipose tissue thickness and echogenicity (as estimated in grey-scale using image analysis software) increased in the late afternoon when compared with those in the morning (1.4 [1.1-1.7] mm vs. 1.4 [1.1-1.8] mm, p < .01; 7.3 [6.0-8.1] mm vs. 7.3 [6.1-8.3] mm, p < .05; and 37.3 [31.5-39.4] vs. 39.8 [35.7-44.1], p < .01, respectively). Diameters of leg veins such as the great saphenous vein, small saphenous vein and dorsal vein of the foot were all reduced towards late afternoon (p < .01 each). Sonography quantitatively and precisely detected physical changes associated with physiological lower leg oedema after daytime activity in healthy young women., (© 2020 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Neck and upper-back stiffness is a common discomfort encountered occasionally in daily life among otherwise healthy subjects. The pathogenesis of this condition could be attributable to increased tension in muscles such as the trapezius muscle (TM). The transverse cervical artery (TCA) is one of the feeding arteries for the TM, and TCA flow is reportedly related to symptoms of neck and upper-back stiffness. This study quantitatively investigated relationships between TM hardness and TCA hemodynamics as evaluated on Doppler sonography. Questionnaires regarding neck and upper-back stiffness, muscle hardness measurements obtained using a muscle hardness meter and examinations of TCA hemodynamics using Doppler sonography were performed on 55 healthy young adults (25 males, 30 females; mean age, 22 ± 2 years). Subjects displaying neck and upper-back stiffness actually exhibited high muscle hardness (median, 14.0; interquartile range (IQR), 12.9-18.0) compared to those without the symptom (median, 12.0; IQR, 9.9-14.0; p = .002). Peak systolic velocity in the TCA on Doppler sonography was lower in subjects with the symptom (median, 65.1 cm/s; IQR 59.6-72.5 cm/s) than in those without the symptom (median, 72.5 cm/s; IQR 66.5-84.2 cm/s; p = .012). Resistive index in the TCA was high (r 2  = .605, p = .014) with increasing TM hardness, particularly among male subjects with the symptom. The present study suggests that high resistance and low blood flow velocity in the TCA could be closely associated with the underlying pathogenesis of neck and upper-back stiffness., (© 2020 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Renal artery stenosis (RAS) is the most common cause of secondary hypertension, via increases in plasma renin-angiotensin-aldosterone levels. Renal artery stenosis is diagnosed from blood examinations such as renin activity and from imaging examinations such as sonography. Patients are required to lie on the bed for 30 min before and during phlebotomy, since plasma renin activity is easily altered by posture. However, no such pre-examination rest is required for sonography. The present study therefore investigated the possible influence of resting before examination on Doppler parameters used for the diagnosis of RAS. Subjects comprised 55 healthy young adults (24 males, 31 females; mean age, 22 ± 1 years). Sonographic measurements were made shortly after subjects entered the examination room and again after 30 min of rest lying on a bed. Median peak systolic velocity in the renal artery was significantly decreased after rest (106 cm/s, interquartile range (IQR) 96-121 cm/s) compared with before rest (120 cm/s, IQR 107-135 cm/s; p < .001). Median acceleration time in the intra-renal segmental artery was also significantly shorter after rest (49 ms, IQR 38-54 ms) compared to before rest (50 ms, IQR 38-59 ms; p = .039). The present results suggest that serious consideration should be given regarding whether pre-examination resting is needed to accurately interpret Doppler measurements of renal blood flow when diagnosing RAS from sonography., (© 2020 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Hemodynamics is subject to change after eating meals, which may be related to various postprandial physical statuses such as hypotension or daytime sleepiness. Previous studies have shown that blood flow in the superior mesenteric artery (SMA) increases after meals, but conflicting results have been reported regarding blood flow in the common carotid artery (CCA). In those studies, the fasting interval before the meal was not taken into account. For example, eating breakfast shortly before lunch may affect hemodynamics in these vessels. The present study therefore investigated hemodynamics in the CCA and SMA after lunch, comparing cases with and without breakfast. Subjects comprised 24 healthy young adults (mean age, 22 ± 1 years). Duplex Doppler sonography was performed to measure blood flow values for calculating flow volume (FV) before and after lunch until 3 h postprandially, on each day with breakfast and without breakfast, respectively, in every subject. Net FV after lunch did not differ between cases with and without breakfast, either in the SMA or in the CCA. Blood FV in the SMA was significantly increased after eating lunch regardless of whether breakfast was eaten (P<0·05 each). However, FV in the CCA was significantly decreased until 1 h after lunch compared with the preprandial state in cases without breakfast (P<0·05), but not in cases with breakfast. In conclusion, a sudden decrease in FV in the CCA from the preprandial state is seen after lunch when breakfast is skipped., (© 2018 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Splanchnic blood flow changes dramatically after meal ingestion. The present study evaluated physiologic interactions between meal ingestion and hemodynamics with respect to renal blood flow on duplex sonography, assessing the possible influence on Doppler parameters used as diagnostic criteria for renal artery stenosis. Subjects comprised 26 healthy young men (mean age: 22 ± 2 y). Sonographic measurements were made shortly after breakfast and every 1 h thereafter and were compared with values measured before the meal. Peak systolic velocity in the renal artery was elevated post-prandially, peaking at 1 h (90 ± 12 cm/s), compared with pre-prandially (73 ± 10 cm/s, p < 0.01). Similarly, acceleration time at the intra-renal segmental artery shortened to a minimum at 1 h (45 ± 5 ms) compared with baseline (51 ± 6 ms, p < 0.01). The present study indicates that renal blood flow is altered for a few hours after meal ingestion. Attention should be paid to the interpretation of data measured after meals on duplex sonography for diagnosis of renal artery stenosis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Carotid artery stenting (CAS) has been developed as an alternative therapeutic strategy for carotid endarterectomy (CEA) for the past several decades. One of the remaining issues of CAS is the relatively higher incidence of ipsi-lateral stroke after the procedure compared with CEA. Ischemic stroke after CAS sometimes occurred after catheterization, and a major cause of delayed stroke has been hypothesized to be stent-thrombosis. In this report, we present a case of a delayed plaque protrusion observed by contrast enhanced computed tomography and intravascular ultrasound, which could be the cause of the delayed recurrence of ischemic symptom. The lesion required an additional endovascular treatment to relieve the patient of the recurrence. This phenomenon might be a possible reason for the delayed ischemic stroke after CAS.

Sodium permanganate, sodium picrate (NaPic), Bu(4)NPic, Me(4)NPic, and Et(4)NPic were extracted at an ionic strength of 2 × 10(-5) to 0.08 mol dm(-3) and 25°C from water (w)-phases into the organic (o)-ones, 1,2-dichloroethane (DCE) and nitrobenzene (NB). Thereby, apparent distribution constants (K(D,±)) of the anions (A(-)) or the cations (M(+)) and ion-pair formation ones (K(MA)(org)) of the univalent salts (MA) in the o-phases were determined at 25 °C, where K(D,±) = ([A(-)](o)[M(+)](o)/[A(-)][M(+)])(1/2) = (K(D,A)K(D,M))(1/2) and K(MA)(org) = [MA](o)/[M(+)](o)[A(-)](o). Also, the K(ex) and K(D,MA) values with A(-) = Pic(-), MnO(4)(-) were estimated from the relations K(ex) (= [MA](o)/[M(+)][A(-)]) = K(MA)(org)(K(D,±))(2) and = K(MA)K(D,MA), respectively. Standard potentials (Δψ(tr)(0)) for ion transfers at the w/DCE and w/NB interfaces were evaluated from the log K(D,A) or log K(D,M) values by assuming the relations K(D,Pic) = K(D,Et4N) and = K(D,Me4N), respectively. The thus-obtained Δψ(tr)(0) values, especially for the w/DCE system, were in good agreement with the values based on the extra-thermodynamic assumption for Ph(4)As(+) and BPh(4)(-) transfers at the interfaces. In the present extraction systems, the ion-pair formation of MA in the w- and o-phases was less effective in the determination of their distribution constants into the two o-phases., (2011 © The Japan Society for Analytical Chemistry)

The 'solar experience' as an abnormal experience of schizophrenia in which patients directly experience the sun itself was first described by Miyamoto in 1974. Patients have delusions of the sun dying, hallucinations of the sun, and even believe that they become the sun. The patient may draw pictures of the sun similar to Edvard Munch's famous painting "The Sun". Miyamoto explained the progression of the solar experience as follows: (1) in the early stage of schizophrenia, patients believe that the sun falls or dies; (2) in the midst of the illness, they occupy the position of the sun in their delusions; and (3) in the recovery stage, they see or draw the sun against a scenic background, indicating that they no longer perceive themselves to be at the center of the world. Because of the absolute centrality of the sun, Miyamoto noted that the patient never experiences multiple suns (a 'polysolar experience'). However, in his book Memoirs of My Nervous Illness (original German title: Denkwürdigkeiten eines Nervenkranken), Daniel Paul Schreber described that he saw two suns. In this paper, the authors report two patients with schizophrenia who presented with a solar experience. Patient 1 was a man in his early forties. Fourteen years before his 'polysolar experience', he had attempted suicide, developed stupor, and was diagnosed with depression. However, he sometimes exhibited cenestopathy. Three years before the experience, he developed catatonic stupor and auditory hallucinations, and his diagnosis was changed to schizophrenia. After two months of hospitalization, the patient, in partial remission, was discharged. Ten months later, he saw two fragments tumble down from the sun, which he described as sons of the sun. Thereafter, his behavior became erratic, which led to a third hospitalization. In the recovery phase, the patient drew a picture of a large sun covering the entire piece of drawing paper and another of the sun set in scenery. Patient 2 was a married woman in her late thirties. She developed delusions of persecution during high school. She managed to cope with the delusions over the next several years, until she experienced an acute psychotic episode while studying in an Asian country. After returning to Japan, she began treatment for schizophrenia. Her first marriage failed, and she later experienced marital problems in her second marriage. She hoped that having a baby would solve these problems, but neuroleptic-induced hyperprolactinemia made her infertile. She stopped taking the neuroleptics and had delusions, including that she was loved by the Crown Prince of Japan and that they would be married, and that her husband was an imposter and assassin. During a 4-month period of hospitalization, she repeatedly drew pictures of multiple suns. In the recovery phase, she drew the sun set in scenery but assigned it a specific area set apart from the rest of the picture. The solar experience of Patient 1 follows a relatively typical course which Miyamoto schematized. The patient's experience of a fragmented sun is equivalent to the fall or death of the sun, and was thought to occur in the transition between the first and second stages of the progression of the solar experience. The polysolar drawings of Patient 2 were also produced in the period between the first and second stages, where the multiple suns might signify the patient's ideal partner among many imposters.

Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, not only improves insulin resistance and glycemic control, but may also have additional beneficial vascular effects in patients with type 2 diabetes mellitus. We investigated whether pioglitazone had an influence on arterial stiffness, which is an independent predictor of cardiovascular events, in 204 patients with type 2 diabetes mellitus. A prospective, nonrandomized, open-label trial was performed that involved 41 patients treated with pioglitazone, 46 patients receiving sulfonylureas, 67 patients on insulin, and 50 patients on diet/exercise only. The follow-up period was 56 +/- 3 months. Arterial stiffness was evaluated by using the arterial stiffness index (ASI), which was based on analysis of the pulse wave amplitude pattern obtained during automated blood pressure measurement in the upper limb. The 4 groups had a similar baseline ASI, which was greater than the reference range in each group. Although antidiabetic therapies improved hemoglobin A(1c) and low-density lipoprotein cholesterol, ASI only decreased significantly in the pioglitazone group. Thus, pioglitazone improved abnormal arterial stiffness in patients with type 2 diabetes mellitus via a mechanism beyond the metabolic improvement. These findings may have important clinical implications in the use of pioglitazone in patients with type 2 diabetes mellitus.

Purpose: The therapeutic and adverse effects of pre-operative chrono-chemoradiation with local hyperthermia for patients with rectal adenocarcinoma were evaluated., Materials and Methods: Pre-operative radiation therapy of a total dose of 40 Gy (n = 10) or 50 Gy (n = 19) on the whole pelvis and hyperthermia once a week during the radiation therapy for 1 h were performed for patients with T2-T4 rectal adenocarcinoma. Chemotherapy consisted of 5-FU (250 mg m-2 per day) and LV (25 mg m-2 per day) administered by continuous infusion in the night for 5 days a week in the second and fourth weeks of radiation., Results: Grade 3+ toxicities were seen only in two patients (6.9%). A significant down staging was seen in 41.4% of all cases and 52.6% of cases with a radiation dose of 50 Gy. Of the patients who had received surgical resection of a tumour, three (11.1%) had no residue pathologically in the specimen and eight (29.6%) had microscopic lesions., Conclusions: These results yielded a high response rate with minimal toxicities for advanced low-rectal adenocarcinoma. The administration of 5-FU during the sleeping time before irradiation might have an advantage not only as a chronotherapy but also as a radiation sensitizer.

Purpose: Several investigations have revealed that the alpha/beta ratio for prostate cancer is atypically low, and that hypofractionation or high-dose-rate (HDR) brachytherapy regimens using appropriate radiation doses may be expected to yield tumor control and late sequelae rates that are better or at least as favorable as those achieved with conventional radiation therapy. In this setting, we attempted treating localized prostate cancer patients with HDR brachytherapy combined with hypofractionated external beam radiation therapy (EBRT). The purpose of this study was to evaluate the feasibility of using this approach, with special emphasis on the relationship between the severity of acute genitourinary (GU) toxicity and the urethral dose calculated from the dose-volume histogram (DVH) of HDR brachytherapy., Methods and Materials: Between September 2000 and December 2003, 70 patients with localized prostate cancer were treated by iridium-192 HDR brachytherapy combined with hypofractionated EBRT at the Gunma University Hospital. Hypofractionated EBRT was administered in fraction doses of 3 Gy, three times per week; a total dose of 51 Gy was delivered to the prostate gland and the seminal vesicles using the four-field technique. No elective pelvic irradiation was performed. After the completion of EBRT, all the patients additionally received transrectal ultrasonography (TRUS)-guided HDR brachytherapy. The fraction size and the number of fractions in HDR brachytherapy were prospectively changed, whereas the total radiation dose for EBRT was fixed at 51 Gy. The fractionation in HDR brachytherapy was as follows: 5 Gy x 5, 7 Gy x 3, 9 Gy x 2, administered twice per day, although the biologic effective dose (BED) for HDR brachytherapy combined with EBRT, assuming that the alpha/beta ratio is 3, was almost equal to 138 in each fractionation group. The planning target volume was defined as the prostate gland with 5-mm margin all around, and the planning was conducted based on computed tomography images. The number of patients in each fractionation group was as follows: 13 in the 5-Gy group; 19 in the 7-Gy group, and 38 in the 9-Gy group. The tumor stage was T1 in 10 patients, T2 in 36 patients, and T3 in 24 patients. The Gleason score was 2-6 in 11 patients, 7 in 34 patients, and 8-10 in 25 patients. Androgen ablation was performed in all the patients. The median follow-up duration was 14 months (range 3-42 months). The toxicities were graded based on the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity criteria., Results: The main symptoms of acute GU toxicity were dysuria and increase in urinary frequency or nocturia. The grade distribution of acute GU toxicity in the patients was as follows: Grade 0-1, 39 patients (56%), and Grade 2-4, 31 patients (44%). One patient who developed acute urinary obstruction was classified as having Grade 4 toxicity. Comparison of the distribution of the grade of acute GU toxicity among the different fractionation groups revealed no statistically significant differences among the groups. The urethral dose in HDR brachytherapy was evaluated using the following DVH parameters: V30 (percentage of the urethral volume receiving 30% of the prescribed radiation dose), V80, V90, V100, V110, V120, V130, and V150. The V30-110 values in the patients with Grade 2-4 acute GU toxicity were significantly higher than those in patients with Grade 0-1 toxicity. On the other hand, there were no significant differences in the V120-150 values between patients with Grade 0-1 and Grade 2-4 toxicity. Regarding the influence of the number of needles implanted for the radiation therapy, patients with 11 needles or less showed a significantly higher incidence of Grade 2-4 acute GU toxicity compared with those with 12 needles or more (p < 0.05)., Conclusions: It was concluded that HDR brachytherapy combined with hypofractionated EBRT is feasible for localized prostate cancer when considered from the viewpoint of acute toxicity. Increase in the fraction dose or reduction in the number of fractions in HDR brachytherapy did not affect the severity of acute GU toxicity, and the volume of urethra receiving an equal or lower radiation dose than the prescribed dose was more closely associated with the grade severity of acute GU toxicity than that receiving a higher than the prescribed dose.

Until now, there has not been enough information on how androgens or androgen deprivation may influence the response of cancer cells to radiation. In this study, the effect of dihydrotestosterone (DHT) on cellular proliferative activity and radiosensitivity was examined in a hormone-sensitive human prostate cancer cell line, LNCaP. In addition, the study also examined how a heat shock protein 90 (Hsp90) chaperone complex inhibitor modified the effect of DHT on the radiosensitivity of the cells, because binding of the androgen receptor (AR) to Hsp90 is required to maintain the stability and functioning of AR. The hormone-sensitive human prostate cancer cell line, LNCaP, was used. Radicicol was used as one of the known Hsp90 chaperone complex inhibitors, and the cells were incubated in the presence of this compound at a concentration of 500 nM. Cellular radiosensitivity was determined by the clonogenic assay; the changes in the protein expression were examined by Western blotting or immunofluorescence. DHT at a concentration of 1 nM caused enhancement of the proliferative activity and reduction of the radiosensitivity of the cells. Radicicol at a concentration of 500 nM abolished the DHT-induced decrease in cellular radiosensitivity and potentiated the radiation-induced cell killing synergistically. Consistent with the changes in the cellular radiosensitivity, radicicol degraded AR, Raf-1 and HER2/neu via reduced binding of AR to Hsp90, although selective degradation of HER2/neu caused by Herceptin, a monoclonal antibody against HER2, did not affect the cellular radiosensitivity. The results suggest that the Hsp9O chaperone complex may be a potential molecular target for potentiation of radiation-induced cell killing in a hormone-sensitive prostate cancer cell line.

We investigated the relation of arterial stiffness, considered an independent predictor of cardiovascular events, to cardiovascular risk factors in a population-based study of 1023 subjects. An Arterial Stiffness Index (ASI) was developed to evaluate arterial stiffness based on an analysis of the pulse wave amplitude pattern acquired from measurements of brachial blood pressure. In control subjects (n = 266) without any major risk factors, the ASI was 46 +/- 11, and increased with age (r = 0.346). The ASI was significantly higher in women ranging from 50 to 54 years of age than in age-matched men. The ASI rose in correlation with the number of risk factors. Subjects with two risk factors showed a significantly higher ASI than those without any risk factors (54 +/- 26 vs. 46 +/- 11). The ASI was significantly increased in diabetic subjects with hypertension in comparison to those without hypertension. Furthermore, hyperlipidemic subjects with hypertension showed significantly higher values than those without hypertension. ASI could be a useful predictor of cardiovascular events in hypertensive subjects with multiple risk factors.

Purpose: To investigate the incidence and severity of rectal bleeding after high-dose hypofractionated radiotherapy (RT) for prostate cancer, and to explore the factors affecting the incidence of Grade 2 or worse rectal bleeding., Methods and Materials: The data of 52 patients who had been treated by external beam RT for localized prostate cancer between 1999 and 2002 were analyzed. All the patients had received hypofractionated external beam RT to a total dose of 69 Gy in 3-Gy fractions, three fractions weekly. The clinical and dosimetric factors affecting the incidence of Grade 2 or worse late rectal bleeding were analyzed by univariate and multivariate analyses. The effect of the percentage of the whole rectal volume receiving 30%, 50%, 80%, and 90% of the prescribed radiation dose (V(30), V(50), V(80), and V(90), respectively) on the incidence of rectal bleeding was evaluated., Results: Of the 52 patients, 13 (25%) developed Grade 2 or worse rectal bleeding. One patient who needed laser coagulation and blood transfusion for the treatment of rectal bleeding was classified as having Grade 3 rectal bleeding. The median time to the development of Grade 2 or worse rectal bleeding was 11 months. The results of the univariate analysis revealed that the presence of a history of diabetes mellitus (p < 0.001), and V(30) >/= 60%, V(50) >/= 40% (p < 0.05), V(80) >/= 25%, and V(90) >/= 15% (p < 0.001) were statistically significant risk factors for the occurrence of Grade 2 or worse rectal bleeding. The results of the multivariate analysis revealed that a history of diabetes mellitus was the most statistically significant risk factor for the occurrence of rectal bleeding after hypofractionated RT for prostate cancer (p < 0.05)., Conclusion: A history of diabetes mellitus was the most statistically significant risk factor for the occurrence of Grade 2 or worse rectal bleeding after high-dose hypofractionated RT, although dosimetric factors were also closely associated with the risk of rectal bleeding.

Purpose: To examine the ability of a heat shock protein 90 (Hsp90) chaperone complex inhibitor, radicicol, to modify thermal response and heat-induced cell killing, and to clarify the underlining mechanisms., Materials and Methods: A human oesophageal cancer cell line (TE-1), with a mutant p53 gene, was used. To examine the effect of radicicol on heat-induced cell killing, radicicol at a concentration of 100 nM was incubated with the cells for 7 h during heat treatment. Changes in the expression of proteins were examined by Western blot and immunofluorescence analysis., Results: Radicicol in combination with heat synergistically potentiated heat-induced cellular killing despite an increase in the expression of Hsp72 and Hsp27 caused by radicicol. Heat alone activated Raf-1 and p42/p44 extracellular signal-regulated kinase (Erk), and heat in combination with radicicol inhibited the activation of Raf-1 and p42/p44 Erk through reduced binding of Raf-1 to Hsp90. Phosphorylation of Akt was also decreased by radicicol., Conclusions: The Hsp90 chaperone complex inhibitor, radicicol, potentiated heat-induced cellular killing, and inhibition of p42/p44 Erk and Akt activation rather than modification of Hsp expression might be involved in enhancing cellular thermosensitivity. Results suggest that the Hsp90 chaperone complex could be a new molecular target for the modification of the cellular response to heat.

Purpose: To analyze the results of clinically node-negative, localized hormone-refractory prostate cancer treated with external beam radiotherapy (EBRT) and to investigate the potential prognostic factors that influenced the therapeutic outcome., Methods and Materials: Fifty-three patients who had developed localized hormone-refractory prostate cancer were treated with EBRT between 1994 and 2001. According to the 1992 American Joint Committee on Cancer clinical stage, 4 patients had T2 and 49 had T3 at the start of RT, and 14 patients had a Gleason score <7, 14 had a Gleason score of 7, and 23 had a Gleason score of 8-10. All patients were treated with EBRT using the unblocked oblique four-field technique, with a total dose of 69 Gy. The fraction dose was 3 Gy three times weekly. The median follow-up after RT was 35 months (range, 8-96 months) and after androgen ablation was 73 months (range, 42-156 months)., Results: Of 53 patients, 15 patients subsequently developed clinical relapse, including locoregional and/or distant metastases. The site of first relapse was bone metastasis in 10, lymph nodes in 3, and local failure in 2 patients; 3 patients died of prostate cancer during the analysis period. The 3-year and 5-year cause-specific survival rate was 94% and 87%, respectively, and the 3-year and 5-year clinical relapse-free survival rate was 78% and 56%, respectively. The univariate analysis revealed that a short prostate-specific antigen (PSA) doubling time and high PSA value at the start of RT and a high Gleason score were statistically significant factors for the risk of clinical relapse. Multivariate analysis demonstrated that the PSA value (PSA or=15 ng/mL) at the start of RT was an independent prognostic factor., Conclusion: EBRT could be a treatment of choice for clinically node-negative, localized, hormone-refractory prostate cancer.

Purpose: The purpose of this study was to examine how selective inhibition of the survival signal transduction pathways affects radiosensitivity in human cancer cell lines., Materials and Methods: Two human esophageal cancer cell lines, TE-1 (mutant p53) and TE2 (wild-type p53), were used. To inhibit the pathways selectively, 3 specific kinase inhibitors, AG1478 (an inhibitor of EGFR), PD98059 (an inhibitor of MEK) and LY294002 (an inhibitor of PI3K), were combined with radiation., Results: Radiation in combination with these kinase inhibitors potentiated radiation-induced cell killing synergistically. Enhancement ratios were greater in TE-2 than those in TE-1. Radiation in combination with kinase inhibitors increased the expression of the active form of caspase-3 and the PARP cleavage only in TE-2 that has wild-type p53., Conclusion: Targeting the key molecules of the survival signal transduction pathway resulted in potentiation of radiation-induced cell killing. The results of this study suggest that the survival signal transduction pathways would be a molecular target in enhancing radiosensitivity.

Purpose: The aim of the study is to develop high-dose-rate (HDR) conformal interstitial brachytherapy by means of combined CT-fluoroscopy guidance with CT-based treatment planning for locally recurrent rectal carcinoma., Methods and Materials: Brachytherapy needle insertion was guided with a helical CT scanner providing continuous fluoroscopy reconstruction. A video monitor placed adjacent to the CT gantry simultaneously allowed the operator to see the process of needle insertion. Final CT images were transferred by an online system to the treatment-planning computer, which reconstructed the implant needles and organ contours. The doses in planning target volume were normalized and geometrically optimized. The patients received a brachytherapy dose at 5 Gy twice daily with a hypofractionated accelerated schedule at a total dose of 30-50 Gy with or without external radiation therapy. Eighteen patients were treated with this procedure., Results: Ten to thirty-six needles (average, 17.3) were successfully placed to the planning target volume in each patient. The average time for CT fluoroscopy was 357 seconds for each procedure. No accident was seen at needle insertion, but 2 patients developed incomplete peroneal nerve palsy after needle removal, but gradually recovered. CT-based treatment planning was faster and more accurate than projection reconstruction with conventional radiograms. Analysis of the dose volume histogram showed conformal dose distribution to the target, while avoiding normal structures., Conclusion: CT fluoroscopy guidance ensures safety and increases the accuracy of needle placement in brachytherapy. Conformal high-dose-rate (HDR) interstitial brachytherapy with CT-based treatment planning is a method worth considering for locally recurrent rectal cancer.

Background: Optimal timing of the measurement of serum squamous cell carcinoma (SCC) antigen during radiation therapy (RT) and its significance for predicting the response of cervical carcinoma patients as early as possible remain unknown., Methods: Sixty-three patients with SCC of the uterine cervix who received RT only were studied. Patients were treated with a combination of external beam irradiation and high-dose rate intracavitary irradiation. The serum SCC antigen level was measured before, every 2 or 3 weeks during, and 1 or 2 months after RT. Clinical outcome was divided into complete response and incomplete response., Results: Forty-seven patients (74.6%) had serum SCC antigen levels 1.5 ng/mL (the reference value) before RT. Normalization of serum SCC antigen levels at the end of RT were found to be significantly correlated with complete response in the SCC-positive patients. It was especially noted that in patients with serum SCC levels between 5-30 ng/mL before RT, a > 70% decrease in the serum SCC antigen level at 4 weeks was correlated significantly with complete response. In this group, a significant correlation also was found between a > 70% decrease in serum SCC level at 4 weeks and the normalization of SCC at the end of RT., Conclusions: The current study data suggest that the serum SCC antigen level not only before, but also during and at the end of RT can predict the response of patients with cervical carcinoma and help in identifying those patients who are at high risk of local recurrence and/or distant metastasis., (Copyright 2003 American Cancer Society.)

Purpose: The aim of this study was to investigate the cell killing induced by low dose-rate irradiation (LDRI) simultaneously combined with long duration mild hyperthermia in LK87 human lung cancer cells. Cell cycle alteration due to this combined treatment was also observed., Materials and Methods: Human lung adenocarcinoma cells, LK87, were treated with concurrent LDRI (50 cGy/hr) and mild hyperthermia (38 to 42 degrees C). Cell survival was estimated by clonogenic assay. Flow cytometry was performed with FACScan. The treatments were simultaneously performed for up to 48 hr (24 Gy)., Results: Survival curves of mild hyperthermia alone revealed development of chronic thermotolerance up to 48 hr, whereas LDRI plus hyperthermia caused an exponential decrease in survival. The LDRI cytotoxicities were enhanced by mild hyperthermia over a non-lethal temperature range. The Do values calculated from dose response curves at 37, 38, 39, 40, 41 41.5 and 42 degrees C were 6.55, 5.25, 4.24, 3.99, 3.46, 1.83 and 0.70 Gy, respectively. Cell cycle analysis demonstrated a remarkable G2 and a mild G1 block for LDRI alone, but only a G1 block was observed for LDRI combined with 41 degrees C hyperthermia., Conclusion: The LDRI cytotoxicity was enhanced by long duration mild temperature hyperthermia. The suppression of chronic thermotolerance was considered to be a mechanism involved in this sensitization.

Malignant fibrous histiocytomas (MFHs) are mesenchymal tumors, usually arising in soft tissue of the extremities and are remarkably resistant to radiation and chemotherapy. A 45-year-old female presented with a rare case of MFH originating in the cranial bone manifesting as a lump in the left parietal region with no neurological abnormality. Neuroimaging revealed the presence of an osteolytic tumor in the left parietal bone invading into muscle and subdural region, penetrating through the dura. Selective external carotid angiography disclosed a marked tumor stain. Examination of the whole body excluded neoplastic disease elsewhere. The patient was treated by surgical excision, radiation, and two courses of multi-drug chemotherapy using cyclophosphamide, doxorubicin, vincristine, and prednisolone. Since there is no established treatment against this malignancy, a longer follow-up is necessary to determine whether cure has been achieved.

Sixty-one consecutive patients with multiple myeloma were studied with magnetic resonance (MR) imaging of the spine. Sagittal T1-weighted and short inversion time (TI) inversion recovery (STIR) images were obtained. The MR patterns of the bone marrow were classified as diffuse (D) (n=26), nodular (N) (n=11), D+N (n=13) or normal (n) (n=11). Abnormal patterns were seen in 50 (82%) of the 61 patients. Correlations were found between the MR imaging patterns and some laboratory findings (WBC, haematocrit, platelet count, serum albumin, and percentage of marrow plasmacytosis). The survival of the patients with abnormal MRI patterns was significantly poorer than that of the patients with normal patterns. However, the survival of patients with a nodular pattern did not differ from those with a normal pattern. The MR imaging pattern of the bone marrow in patients with multiple myeloma is a useful factor in the assessment of prognosis.

The most important function of carotenoid pigments, especially beta-carotene in higher plants, is to protect organisms against photooxidative damage (G. Britton, in T. W. Goodwin, ed., Plant Pigments--1988, 1988; N. I. Krinsky, in O. Isler, H. Gutmann, and U. Solms, ed., Carotenoids--1971, 1971). beta-Carotene also functions as a precursor of vitamin A in mammals (G. A. J. Pitt, in I. Osler, H. Gutmann, and U. Solms, ed., Carotenoids--1971, 1971). The enzymes and genes which mediate the biosynthesis of cyclic carotenoids such as beta-carotene are virtually unknown. We have elucidated for the first time the pathway for biosynthesis of these carotenoids at the level of enzyme-catalyzed reactions, using bacterial carotenoid biosynthesis genes. These genes were cloned from a phytopathogenic bacterium, Erwinia uredovora 20D3 (ATCC 19321), in Escherichia coli and located on a 6,918-bp fragment whose nucleotide sequence was determined. Six open reading frames were found and designated the crtE, crtX, crtY, crtI, crtB, and crtZ genes in reference to the carotenoid biosynthesis genes of a photosynthetic bacterium, Rhodobacter capsulatus; only crtZ had the opposite orientation from the others. The carotenoid biosynthetic pathway in Erwinia uredovora was clarified by analyzing carotenoids accumulated in E. coli transformants in which some of these six genes were expressed, as follows: geranylgeranyl PPiCrtB----prephytoene PPiCrtE----phytoeneCrtI---- lycopeneCrtY----beta-caroteneCrtZ----zeaxanthinCrtX--- -zeaxanthin-beta- diglucoside. The carotenoids in this pathway appear to be close to those in higher plants rather than to those in bacteria. Also significant is that only one gene product (CrtI) for the conversion of phytoene to lycopene is required, a conversion in which four sequential desaturations should occur via the intermediates phytofluene, zeta-carotene, and neurosporene.

Erythrobacter species OCh 114 is a strictly aerobic bacterium containing bacteriochlorophyll a. Although its growth is dependent on heterotrophic nutrition, light enhances its growth yield and CO2-fixation activity. A new category--aerobic photosynthetic bacteria--is proposed for Erythrobacter species OCh 114.