Impact of pre-brachytherapy magnetic resonance imaging on dose-volume histogram of locally advanced cervical cancer patients treated with radiotherapy including high-dose-rate brachytherapy.

PURPOSE: This study investigated the suitability of brachytherapy technique selection based on pre-brachytherapy magnetic resonance imaging (MRI) findings in cervical cancer by evaluating dose-volume histogram parameters. MATERIAL AND METHODS: We retrospectively evaluated data from 61 patients with cervical cancer who underwent pre-brachytherapy MRI within 7 days before their first high-dose-rate brachytherapy treatment, selected according to pre-brachytherapy MRI findings. Combined intracavitary brachytherapy with interstitial techniques (IC/ISBT) or interstitial brachytherapy (ISBT) were favored treatments for poor-responding tumors after concurrent chemoradiotherapy, asymmetrical tumors, bulky parametrial extensions, bulky primary disease, and extensive paravaginal or distal vaginal involvement. Intracavitary brachytherapy (ICBT) was the preferred treatment for small tumors without extensive involvement of the vagina and parametrium. RESULTS: The median tumor size was 58 mm on pre-treatment MRI and 38 mm on pre-brachytherapy MRI. On pre-brachytherapy MRI, 13 patients had a tumor with severe vaginal invasion, 15 patients presented with an asymmetrical bulky tumor, and 4 patients had bulky residual tumors. IC/ISBT or ISBT were administered to 26 patients (43%). Median equivalent dose in 2 Gy fractions of clinical target volume D90 was 70.8 Gy for all patients. Median clinical target volume D90 in each brachytherapy session exceeded the prescribed dose in both patients treated with ICBT and IC/ISBT or ISBT. Median equivalent dose in 2 Gy fractions of D2cc to the bladder, sigmoid colon, and rectum was 69.5, 52.0, and 58.4 Gy, respectively. All cases remained within the doses recommended for organs at risk. CONCLUSIONS: Pre-brachytherapy MRI may be helpful in selecting suitable candidates for each type of brachytherapy and deliver the recommended doses to the tumor and organs at risk, particularly in cases with large tumors, poor response to concurrent chemoradiotherapy, asymmetrical tumors, severe vaginal invasion, extensive parametrial invasion, and/or corpus invasion.

Acupuncture therapy: mechanism of action, efficacy, and safety: a potential intervention for psychogenic disorders?

Scientific bases for the mechanism of action of acupuncture in the treatment of pain and the pathogenic mechanism of acupuncture points are briefly summarized. The efficacy and safety of acupuncture therapy is discussed based on the results of German clinical trials. A conclusion on the role for acupuncture in the treatment of psychogenic disorders could not be reached.

Involvement of NGF in the rat model of persistent muscle pain associated with taut band.

UNLABELLED: Myofascial pain syndrome (MPS) is an important clinical condition characterized by chronic muscle pain and a myofascial trigger point (MTrP) located in a taut band (TB). However, its pathogenic mechanism is still unclear. We developed an animal model relevant to conditions of MPS, and analyzed the mechanism of the muscle pain in this model. We applied eccentric contraction (EC) to a rat's gastrocnemius muscle (GM) for 2 weeks, and examined the mechanical withdrawal thresholds, histological changes, and expressions and contents of nerve growth factor (NGF). The mechanical withdrawal threshold decreased significantly at the next day of first EC and continued up to 9 days after EC. TBs were palpable at 3 to 8 days after initiation of EC. In EC animals, necrotic and regenerating muscle cells were found significantly more than in control animals. In EC animals, NGF expressions in regenerating muscle cells and NGF contents of GM were significantly higher than control animals. Administration of NGF receptor (TrkA) inhibitor K252a showed significant suppression of mechanical hyperalgesia in EC animals. Repeated EC induced persistent mechanical muscle hyperalgesia associated with TB. NGF expressed in regenerating muscle cells may have an important role in persistent mechanical muscle hyperalgesia which might be relevant to pathogenesis of MPS. PERSPECTIVE: The present study shows that NGF expressed in regenerating muscle cells is involved in persistent muscular mechanical hyperalgesia. NGF-TrkA signaling in primary muscle afferent neurons may be one of the most important and promising targets for MPS.

Public status and prevalence of acupuncture in Japan.

Acupuncture originated in China and is widespread throughout Asia. It is expected that a higher utilization of this remedy exists in these countries compared to Western countries. We conducted annual nationwide surveys from 2003 through 2006 on the utilization of acupuncture in Japan. Face-to-face interviews were conducted with 2000 individuals randomly chosen from the resident database. Annual utilization percentages, based on the number of respondents, from 2003 to 2006 were 6.5%, 4.8%, 6.4%, and 6.7%, respectively, while lifetime experiences determined in each surveys were estimated as 26.7, 19.4, 24.4 and 25.4, respectively. Respondents who had utilized acupuncture and/or moxibustion tended to be older than those who had no experience. Acupuncture was mainly used for musculoskeletal symptoms, and a detailed breakdown of the musculoskeletal symptoms identified in the 2005 survey showed 50.9% for low back pain, 35.9% for shoulder stiffness and 12.0% for knee pain. Reasons given for continuing therapy included the effective amelioration of symptoms, comfort of the procedure and low number of side-effects, while those who decided against continuing cited no improvement of symptoms, cost and lack of time for treatment. In conclusion, annual utilization of acupuncture and/or moxibustion was estimated at more than 6%, and the percentage of those with a lifetime experience was ∼25%, thus demonstrating the relatively higher utilization of the remedy in Japan over utilization in western countries. Application of the treatment for musculoskeletal problems and utilization by the older population were specific standouts of the use of acupuncture and/or moxibustion in Japan.

Acupuncture on the blood flow of various organs measured simultaneously by colored microspheres in rats.

We examined how acupuncture affected the blood flow of muscle, kidney, stomach, small intestine, brain, lung, heart, spleen and liver. Wistar rats anesthetized with urethane (n = 27) were allocated into the control (n = 10), ST-7 (Hsia-Kuan, n = 10) and LI-4 (Hoku, n = 7) groups. To measure organ blood flow, colored microspheres (CMS) were injected through a catheter positioned in the left ventricle and blood samples were drawn from the femoral artery. Yellow CMS (3.6-4.2 x 10(5)) and blue CMS (6.0-6.9 x 10(5)) were injected at intervals of about 30 min. An acupuncture needle (varphi 340 mum) was inserted into the left ST-7 point (left masseter muscle) or the right LI-4 point after the first sampling and left for about 30 min (10 twists at 1 Hz, 2-min intervals). The mean blood flow of nine organs varied widely from 4.03 to 0.20 (ml/min/g). Acupuncture to the ST-7 produced significant changes of the blood flow (percentage change from baseline) in the muscle, kidney, brain and heart (P < 0.05, versus control), but those of LI-4 were not significant. The blood flow of the left masseter muscle after acupuncture to ST-7 (left masseter muscle) tended to increase (P = 0.08). Changes in blood pressure during the experimental periods were almost similar among these three groups. Acupuncture stimulation increases the blood flow of several organs by modulating the central circulatory systems, and the effects differed with sites of stimulation.

Analgesic action of acupuncture and moxibustion: a review of unique approaches in Japan.

The mechanism of acupuncture analgesia (AA) is one of the most widely researched topics in complementary and alternative medicine (CAM) based on modern medical methodology. Endogenous opioid-mediated mechanisms of acupuncture have been well established since the 1970s. In this review, we have covered the progress of AA research by Japanese investigators. In particular, we have reviewed the physiological basis of analgesic effects induced by acupuncture and moxibustion, including the actions of endogenous opioid and diffuse noxious inhibitory controls (DNICs), and the afferent fibers participating in acupuncture and moxibustion stimuli are discussed.

Psycho-educational Horseback Riding to Facilitate Communication Ability of Children with Pervasive Developmental Disorders.

In this study, we applied a novel psycho-educational horseback riding (PEHR) program to the treatment of four Japanese children with pervasive developmental disorders (PDD) in order to facilitate the acquisition of verbal and nonverbal communication skills. The behavioral changes in each child were evaluated using a psychological and behavioral scale. The scale for evaluating the effect of Human-Equips-Interaction on Mental activity (HEIM scale) was designed to assess the behavioral improvement of children based on the following 10 items: Human relationships, Imitation, Emotional expression, Sudden physical movement, Fixative behavior, Adaptation to change, Visual response, Fear or nervousness, and Verbal and nonverbal communication. After taking part in the PEHR program for several months, all subjects showed remarkably improved HEIM scores and marked improvements were observed in eye contact with others (instructors, side walkers, and leaders) in the riding area. A statistical difference was found in items 1, 2, 3, 6, 7, 8, and 9. However, no statistical difference was found in items 4, 5, and 10. As the program progressed, the children showed enhanced verbal and nonverbal communication skills, and became more expressive in their emotional and empathetic interaction with their parents. These observations suggest that the normal functioning of pleasurable emotions and empathy may facilitate further improvements in joint attention, imitation and empathy, and may result in successful verbal expression by PDD children. Therefore, horseback riding can play a very important role in the psycho-educational support required for the communication ability of PDD children.

Do Japanese style acupuncture and moxibustion reduce symptoms of the common cold?

We summarize the results from a series of investigations of Japanese style acupuncture and moxibustion therapies on symptoms of the common cold that have been conducted (FTLE 1999-03, supported by the Foundation for Training and Licensure Examination in Anma- Massage- Acupressure, Acupuncture and Moxibustion). We also discuss the various interventions and concerns that we faced during these investigations. The subjects were students and teachers. The pilot study (FTLE1999) of a two arm (real and non-treatment control) RCT at a Japanese acupuncture school showed that manual acupuncture to a specific needling point at the throat clearly reduced symptoms of the common cold. The first multi-center (five centers) RCT (FTLE 2000) revealed a significant reduction in cold symptoms, by general linear model analysis (between groups, P = 0.024). To reduce the technical variation, we employed indirect moxibustion to the neck points as a uniform intervention in the next project (FTLE 2001) without statistically significant results. Then we elongated the periods of treatment from 2 to a maximum of 12 weeks (FTLE 2002) with different interventions accompanied by 4 weeks follow-up. The results were still not statistically significant. As the final project, we tried to develop a new experimental design for individualized intervention by conducting n-of-1 trials using elderly subjects in a health care center but without detecting a clear effect. In conclusion, the safety of Japanese acupuncture or moxibustion was sufficiently demonstrated; however, a series of clinical trials could not offer convincing evidence to recommend the use of Japanese style acupuncture or moxibustion for preventing the common cold. Further studies are required as the present trials had several limitations.

Analgesic effects of indirect moxibustion on an experimental rat model of osteoarthritis in the knee.

AIMS: The analgesic effects of moxibustion on an experimental model of osteoarthritis of the knee were investigated. METHODS: Male Wistar rats (n=36, 296-421 g) were used. Intra-articular injection of mono-iodoacetic acid (MIA) was performed to induce knee osteoarthritis. Indirect moxibustion was applied to the lateral aspect of the knee joint every other day for 28 days (14 treatments). Weight bearing of the hind legs was measured directly by the downward pressure applied to footplates, using an Incapacitance Tester. Morphine was injected for testing the validity of weight bearing as a pain measure, and naloxone was used to examine the participation of endogenous opioids in the mechanism of moxibustion analgesia. Data were analysed by calculating the area under the curve. RESULTS: Injection of MIA significantly reduced weight bearing. No analgesic effects of moxibustion were observed during the initial 7 days (unpaired t test, P=0.83). Continued moxibustion treatments increased weight bearing at the 14th day significantly, and this effect continued until the end of the experiment on the 28th day (P<0.05). A single moxibustion treatment had no immediate effect on weight bearing. The analgesia due to the cumulative effect of moxibustion was antagonised by naloxone injection. Morphine injection in control MIA injected rats increased weight bearing to the normal range, confirming the validity of the measurements. CONCLUSIONS: These results highlight the importance of repeated moxibustion treatments for pain relief in experimental knee osteoarthritis and suggest the existence of sustained inhibitory modulation by endogenous opioids in the moxibustion group.

Acupuncture regulates leukocyte subpopulations in human peripheral blood.

Acupuncture has recently been attracting more and more people throughout the world as an alternative treatment, however little is known about its physiological activities (i.e. immune system). We examined acupuncture both quantitatively and qualitatively by measuring CD-positive cell counts and cytokine expression levels in the blood, to determine the activity of T cells, B cells, macrophages and natural killer (NK) cells. Fifteen milliliters of peripheral blood obtained from 17 healthy volunteers aged 21-51 years, were analyzed using flow cytometry before and after acupuncture treatment. There was a statistically significant increase in the number of CD2(+), CD4(+), CD8(+), CD11b(+), CD16(+), CD19(+), CD56(+) cells as well as IL-4, IL-1beta and IFN-gamma levels in the cells after acupuncture stimulation of meridian points. These observations indicate that acupuncture may regulate the immune system and promote the activities of humoral and cellular immunity as well as NK cell activity. In this article, we discussed how acupuncture regulated leukocyte numbers and functions since they are considered to be potential indicators for evaluating complementary and alternative medicine.

Relief of low back pain immediately after acupuncture treatment--a randomised, placebo controlled trial.

BACKGROUND: The purpose of this study was to examine the immediate effect of single acupuncture stimulation to the most painful point in patients with low back pain. METHOD: A randomised, evaluator-blinded, sham controlled clinical trial was conducted in which 31 patients with low back pain were randomly allocated to either an acupuncture group (n = 15) or a sham acupuncture group (n = 16). Both acupuncture and sham acupuncture were performed at the most painful point on the lower back of the subjects. For the acupuncture group, a stainless steel needle was inserted to a depth of 20 mm and manually stimulated (sparrow pecking method) for 20 seconds, while for the sham treatment a guide tube without a needle was placed at the point and tapped on the skin. Changes in low back pain were evaluated with a visual analogue scale (VAS) and the Schober test. Participants were also asked if they felt the needling sensation or not. The therapy and the evaluation were independently performed by two different acupuncturists. RESULTS: VAS score and the Schober test score showed significant improvement after treatment as compared with the sham group (P = 0.02, 0.001, respectively). There were no significant differences in the needling sensation between the acupuncture and sham group. CONCLUSION: These results suggest that acupuncture at the most painful point gives immediate relief of low back pain.

Quantitative analysis of muscle hardness in tetanic contractions induced by electrical stimulation in rats.

The purpose of this study was to investigate the in vivo relation between muscle hardness during an electrically induced contracting state and neuromuscular functions (M-wave and developed tension). Sixteen Sprague-Dawley rats were deeply anesthetized with urethane. Muscle hardness was measured quantitatively at the mid-portion of the gastrocnemius (GS) muscle during tetanic contractions induced by electrical stimulation (50 Hz, 100 micros duration) of the sciatic nerve or of the muscle directly. The M-wave was recorded with a pair of wire electrodes inserted into the muscle, and the developed tension was monitored with a push-pull gauge. Muscle hardness, M-wave amplitude and developed tension increased rapidly with the onset of nerve stimulation. Similar but intensity-dependent increases in muscle hardness and tension were observed following direct tetanic stimulation of the muscle. The hardness measured during nerve stimulation was correlated with the amplitude of the M-wave (r = 0.62, P < 0.0001) and the developed tension (r = 0.85, P < 0.0001). These phenomena were suppressed by pancuronium treatment (2 mg/ml, i.v.). These results suggest that muscle tension might be the most important factor for transcutaneously measured muscle hardness induced by tetanic muscle contraction.

How do acupuncture and moxibustion act? - Focusing on the progress in Japanese acupuncture research -.

The mechanisms of action of acupuncture and moxibustion as reported by Japanese researchers are reviewed. The endogenous opioid-mediated mechanisms of electroacupuncture (EA) as used in China are well understood, but these are only one component of all mechanisms of acupuncture. These studies emphasize the similarity of the analgesic action of EA to various sensory inputs to the pain inhibition mechanisms. In Japanese acupuncture therapy, careful detection of the acupuncture points and fine needling technique with comfortable subjective sensation are considered important. The role of polymodal receptors (PMR) has been stressed based on the facts that PMRs are responsive to both acupuncture and moxibustion stimuli, thermal sensitivity is essential in moxibustion therapy, and the characteristics of acupuncture points and trigger points are similar to those of sensitized PMRs. Acupuncture and moxibustion are also known to affect neurons in the brain reward systems and blood flow in skin, muscle, and nerve. Axon reflexes mediated by PMRs might be a possible mechanism for the immediate action of acupuncture and moxibustion. Reports on the curative effects of acupuncture on various digestive and urological disorders are also reviewed briefly.

Influence of surface anesthesia on the pressure pain threshold measured with different-sized probes.

Transcutaneous pressure with pressure probes of arbitrary diameters have been commonly used for measuring the threshold and magnitude of muscle pain, yet this procedure lacks scientific validation. To examine the valid probe dimensions, we conducted physiological experiments using 34 human subjects. Pin-prick pain, pressure pain threshold (PPT) to pressure probes of various diameters, heat pain threshold, and electrical pain threshold of deep tissues were measured before and after application of surface lidocaine anesthesia to the skin surface over the brachioradial muscle in a double-blinded manner. The anesthesia neither affected PPT with larger probes (diameters: 1.6 and 15 mm) nor increased electric pain threshold of deep structures, whereas it diminished pain count in pin-prick test and PPT with a 1.0 mm diameter probe, suggesting that mechanical pain thresholds measured with 1.6 and 15 mm probes reflect the pain threshold of deep tissues, possibly muscle. Pain thresholds to heat did not change after application of the anesthesia. These results suggest that larger pressure probes can give a better estimation of muscular pain threshold.

A proposed experimental model of myofascial trigger points in human muscle after slow eccentric exercise.

BACKGROUND: The purpose of this study was to develop an experimental model of myofascial trigger points to investigate their pathophysiology. METHODS: Fifteen healthy volunteers who gave informed consent underwent repetitive eccentric exercise of the third finger of one hand (0.1 Hz repetitions, three sets at five minute intervals) until exhaustion. Physical examination, pressure pain threshold, and electrical pain threshold of the skin, fascia and muscle were measured immediately afterwards and for seven days. Needle electromyogram (EMG) was also recorded in a subgroup of participants. RESULTS: Pressure pain thresholds decreased to a minimum on the second day after the exercise, then gradually returned to baseline values by the seventh day. On the second day, a ropy band was palpated in the exercised forearm muscle and the electrical pain threshold of the fascia at the palpable band was the lowest among the measured loci and tissues. Needle EMG activity accompanied with dull pain sensation was recorded only when the electrode was located on or near the fascia of the palpable band on the second day of exercise. CONCLUSION: These results suggest that eccentric exercise may yield a useful model for the investigation of the myofascial trigger points and/or acupuncture points. The sensitised nociceptors at the fascia of the palpable band might be a possible candidate for the localised tender region.

Preventive and curative effects of acupuncture on the common cold: a multicentre randomized controlled trial in Japan.

OBJECTIVE: To determine the preventive and curative effects of manual acupuncture on the symptoms of the common cold. METHOD: Students and staff in five Japanese acupuncture schools (n=326) were randomly allocated to acupuncture and no-treatment control groups. A specific needling point (Y point) on the neck was used bilaterally. Fine acupuncture needles were gently manipulated for 15 s, evoking de qi sensation. Acupuncture treatments were performed four times during the 2-week experimental period with a 2-week follow-up period. A common cold diary was scored daily for 4 weeks, and a common cold questionnaire was scored before each acupuncture treatment and twice at weekly intervals. A reliability test for the questionnaire was performed on the last day of recording. RESULTS: Five of the 326 subjects who were recruited dropped out. The diary score in the acupuncture group tended to decrease after treatment, but the difference between groups was not significant (Kaplan-Meier survival analysis, log rank test P=0.53, Cox regression analysis, P>0.05). Statistically significantly fewer symptoms were reported in the questionnaire by the acupuncture group than control group (P=0.024, general linear model, repeated measure). Significant inter-centre (P<0.001, general linear model) and sex (P=0.027, general linear model) differences were also detected. Reliability tests indicated that the questionnaire with 15 items was sufficiently reliable. No severe adverse event was reported. CONCLUSION: This is the first report of a multi-centre randomized controlled trial of acupuncture for symptoms of the common cold. A significantly positive effect of acupuncture was demonstrated in the summed questionnaire data, although a highly significant inter-centre difference was observed. Needling on the neck using the Japanese fine needle manipulating technique was shown to be effective and safe. The use of acupuncture for symptoms of the common cold symptoms should be considered, although further evidence from placebo controlled RCTs is required.

Effect of indomethacin on the development of eccentric exercise-induced localized sensitive region in the fascia of the rabbit.

The effect of indomethacin on the development of delayed onset muscle soreness (DOMS) and localized sensitive region produced by eccentric exercise was examined in lightly anesthetized rabbits (n=12, 2.0-3.3 kg). Repeated eccentric contractions of the gastrocnemius (GS) muscle were made by manual extensions during the tetanic contractions induced by electrical stimulation of the tibial nerve. The development of DOMS was confirmed by evoked reflex EMG in the biceps femoris (BF) muscle elicited by a quantitative manual extension of the GS muscle. The distribution of thresholds for the evoked BF EMG was measured by focal electrical stimulations of the GS muscle. Indomethacin (5 mg/kg in 2% sodium bicarbonate) or a vehicle was injected subcutaneously before, during, and after the exercise (a total of 60 mg/kg in 12 doses). A clear ropy taut band was palpated at the GS muscle on the second day after the exercise and a localized sensitive region for evoked BF EMG was detected at the depth of the fascia of the band in the exercise and vehicle groups, whereas no such phenomena appeared in the control and indomethacin groups. The palpable band and sensitive region disappeared on the seventh day after the exercise. That indomethacin inhibits the development of DOMS and the localized sensitive region suggests that a sensitization of polymodal-type nociceptors in the fascia mediated by prostaglandins is a possible mechanism for the development of DOMS and the localized sensitive region.

Analgesic effects induced by TENS and electroacupuncture with different types of stimulating electrodes on deep tissues in human subjects.

Effects of conditioning peripheral nerve stimulation with different types of stimulating electrodes on pain thresholds in various deep tissues were measured in human subjects. Cone-shaped metal (phi 13 mm), rubber (phi 13 mm), and large soft surface electrodes (50 x 150 mm) were used for transcutaneous electrical nerve stimulation (TENS), and insulated and non-insulated acupuncture needles (diameter: 240 microns) were used for electroacupuncture (EA). Two pairs of electrodes were placed around the point of deep pain measurement. Symmetrical positive and negative square pulses (0.1 msec at 100 Hz) of just below the pain tolerance intensity were used for both TENS and EA. Deep pain thresholds were measured at the center of the thigh with a pulse algometer and insulated needle electrodes. Pain thresholds of deep tissues were in the order periosteum < fascia < skin (including subcutaneous tissues) < muscle. TENS with surface electrodes significantly increased pain thresholds of skin and fascia but not those of muscle or periosteum. The shape, material and size of the surface electrodes hardly affected the degree of analgesic effect, except in the fascia by large soft electrodes. In contrast, EA with non-insulated needles induced a greater increase in pain threshold in skin, fascia and muscle, although statistically significant results were obtained in only the first two tissues. EA with insulated needle electrodes was the only technique with which we obtained a significant increase in pain threshold in muscle and periosteum. These results suggest that the choice of electrode and stimulus parameters is important for the production of sufficient analgesic effects in different somatic tissues and that insulated needle electrodes are useful for pain relief in deeper tissues such as muscle and periosteum.

Deep pain measurement at tender points by pulse algometry with insulated needle electrodes.

Deep pain thresholds of the tender points in man were measured by pulse algometry. In this technique an insulated acupuncture needle (180 microns in diameter, about 400 k omega at 1 kHz) was used as a cathodal monopolar stimulating electrode. The stimulus consisted of a short train (three 1 msec duration pulses at 500 Hz) repeated at 2 Hz, and the current intensity was increased at a constant rate by a command voltage supplied to the stimulator. The stimulus current was monitored on an oscilloscope, and the integrated current was recorded simultaneously on a chart recorder. The tender points were detected by careful palpation, a pressure algometer being used to quantify threshold intensities. The needle electrode was inserted into the same points and deep pain thresholds were measured every 1-2 mm in depth. The deep pain thresholds at the depth where the experimenter felt some stiffness against the needle insertion (what we have termed needling stiffness) were 0.9 +/- 0.1 mA (mean +/- S.E.M., n = 14). Threshold values determined by repetitive measurements at the same position at intervals of 5 min for 6 successive trials were very similar. The stimulus evoked sensation was a dull-heavy deep pain. The pain thresholds changed markedly as the depth of the electrode tip was changed by 1-2 mm (P less than 0.01, t test). The minimum pain threshold under the tender point occurred at the depth of the needling stiffness. Observations with an ultrasonic image scanner suggested that the needle tip was located on or near the fascia when the experimenter felt the needling stiffness.(ABSTRACT TRUNCATED AT 250 WORDS)