bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Natural History of Back Pain after a Randomised Controlled Trial of Acupuncture Vs Usual Care – Long Term Outcomes
Authors: Prady Stephanie L , Thomas Kate , Esmonde Lisa , Crouch Simon , MacPherson Hugh 
Published: April 2009

Introduction There is growing evidence about the effectiveness of acupuncture in the short term treatment of chronic low back pain but little is known about long term outcomes. To address this question we followed up participants of a past randomised controlled trial of acupuncture to assess outcomes after 5.5 to 7 years. Methods A postal questionnaire assessing pain, quality of life, disability, experience with back pain and healthcare resource use was sent to all 239 participants of the York Acupuncture for Back Pain trial. Results Response to the survey was low at 43.9%. Pain measured by the SF-36 Bodily Pain dimension was maintained in the acupuncture group since the last follow up 3.5 to 5 years previously. The usual care group had improved over the intervening years and there was now no evidence of a difference between the groups (difference −0.4 points, 95% confidence interval −10.1 to 9.7). The results were unchanged on sensitivity analysis using multiple imputation. In both groups back pain had not completely resolved and worry about back health was moderate. Physiotherapy and acupuncture were used at similar rates for continuing treatment. Discussion We theorise that exposure to a short course of acupuncture speeds natural recovery from a back pain episode, but improvements plateau after two years. Acupuncture is often accessed privately for long term management of back pain but is rarely available within the health service. While our study methods were robust, the low response rate means that our findings should be interpreted with caution.
Point Injection as An Alternative Acupuncture Technique – An Exploratory Study of Responses in Healthy Subjects
Authors: Strudwick Mark W , Hinks Roderick C , Choy S T Boris 
Published: April 2009

Introduction Point injection as a therapeutic technique is well documented, but its physiological effects have not been formally compared with traditional acupuncture. One aim of this study was to compare the effects of the two techniques at one acupuncture point, as a step towards understanding the mode of action of point injection and validating its clinical use. A second aim was to explore whether repeated point injection at the same site might provide a way of increasing the dose of stimulation, in the hope of identifying a dose response curve which could be an alternative strategy to placebo control in demonstrating the biological effects of acupuncture. Methods Sixty nine healthy subjects (age range 18–56 years, mean 29.9; 48 females) completed the study, which employed a counterbalanced experimental design with two stimulation sessions of LI4 approximately one week apart. One half of the participants received point injection first, and the other half received traditional acupuncture first. Baseline physiological data were recorded, then measurements were made before, during and after stimulation; each subject also reported needle sensation ( de qi). The measures were heart rate, derived pressure rate product and mean arterial pressure. Results Although stronger sensations of de qi were reported with point injection, no significant differences were found for mean heart rate (HR), pressure rate product (PRP) and mean arterial pressure (MAP) before and after stimulation by the two techniques. No subject gender or age bias was encountered and previous exposure to acupuncture had no effect on outcome. Power spectral analysis of heart rate variability (HRV) made on data from a small subset (n=10) of this cohort also showed no significant differences in autonomic response. Conclusion Point injection and traditional acupuncture seem to provoke similar physiological responses, although the greater needle sensation seen with point injection might indicate it could have more powerful clinical effects. Further studies of repeated point injection are necessary to indicate whether this technique may provide a method of increased strength of point stimulation, as an alternative to traditional needling in acupuncture research.
Trigger Point Acupuncture for Treatment of Knee Osteoarthritis – a Preliminary Rct for a Pragmatic Trial
Authors: Itoh Kazunori , Hirota Satoko , Katsumi Yasukazu , Ochi Hideki , Kitakoji Hiroshi 
Published: April 2009

Background There is evidence for the efficacy of acupuncture treatment in knee osteoarthritis, but it remains unclear which acupuncture modes are most effective. We evaluated the effects of trigger point acupuncture on pain and quality of life in knee osteoarthritis patients, compared with acupuncture at standard points, and sham acupuncture. Methods Thirty patients (27 women, 3 men; aged 61–82 years) with non-radiating knee osteoarthritis pain for at least six months and normal neurological examination were randomised to one of three groups for the study period of 21 weeks. Each group received five acupuncture treatment sessions. The standard acupuncture point group ( n=10) received treatment at traditional acupuncture points for knee pain; the trigger point acupuncture group ( n=10) received treatment at trigger points; and the third group ( n=10) received sham acupuncture treatment at the trigger points. Outcome measures were pain intensity (visual analogue scale, VAS) and WOMAC index (Western Ontario and McMaster Universities Arthritis Index). The groups were compared by the area under the curve method. Results Five patients dropped out of the study because of lack of improvement, and one patient (in the trigger point acupuncture group) dropped out because of deterioration of symptoms; the remaining 24 patients were included in the analysis. After treatment, the trigger point acupuncture group reported less pain intensity on VAS than the standard acupuncture or sham treatment group, but both the trigger point acupuncture and standard acupuncture groups reported improvement of function of knee. There was a significant reduction in pain intensity between pre-treatment and five weeks after treatment for the trigger point acupuncture (P<0.01) and standard acupuncture groups (P<0.01) included in the analysis, but not for the sham treatment group. Group comparison using the area under the curves demonstrated a significant difference only between trigger point acupuncture and sham treatment groups analysed (P<0.025 for VAS, and P<0.031 for WOMAC). Conclusion These results suggest that trigger point acupuncture therapy may be more effective for osteoarthritis of the knee in some elderly patients than standard acupuncture therapy.
Pudendal Nerve Electroacupuncture for Lumbar Spinal Canal Stenosis – a Case Series
Authors: Inoue Motohiro , Hojo Tatsuya , Nakajima Miwa , Kitakoji Hiroshi , Itoi Megumi , Katsumi Yasukazu 
Published: April 2009

Objective To investigate the effectiveness of pudendal nerve electroacupuncture for lumbar and lower limb symptoms in patients with lumbar spinal canal stenosis for whom acupuncture of the lumbar and lower limb muscles had been ineffective. Methods Nine patients with lumbar spinal canal stenosis for whom conventional acupuncture at the lumbar and lower limb muscles had no effect. Pudendal nerve electroacupuncture was performed eight times (once per week). VAS scores and continuous walking distance were used to evaluate changes in symptoms. Results The following changes in symptoms occurred after pudendal nerve electroacupuncture: low back pain was improved from 45.3±17.4mm (mean ± SD) to 39.2±14.0mm, lower limb pain was improved from 61.1±5.6mm to 35.4±11.9mm, lower limb dysaesthesia was improved from 63.9±8.4mm to 46.9±16.2mm, and continuous walking distance was improved from 100.0±35.4m to 250.0±136.9m. Conclusion Pudendal nerve electroacupuncture may be an effective treatment for lumbar and lower limb symptoms due to spinal canal stenosis, and is potentially useful in patients who have not responded to conventional acupuncture.
Effects of Minimal Acupuncture in Children with Infantile Colic – a Prospective, Quasi-Randomised Single Blind Controlled Trial
Authors: Reinthal Marianne , Andersson Sven , Gustafsson Marianne , Plos Kaety , Lund Iréne , Lundeberg Thomas , Rosén Karl Gustaf 
Published: April 2009

Background Colic causes crying in 10–30% of infants and is one of the primary reasons parents seek health care. Treatments are generally not totally effective and some cause side effects. In this study we aimed to test the effect of light needling (minimal acupuncture) on crying. Methods Forty children (median six weeks of age) with excessive crying unresponsive to conventional therapies, were recruited from 21 Child Welfare Clinics within an area of western Sweden, and quasi-randomised to control or light needling treatment. Parents were unaware of which group their child was assigned to. Children were given light needling acupuncture on one point (LI4) on both hands for approximately 20 seconds on four occasions, or received the same care except needling. Parental assessment questionnaires were used pre- and post-treatment to assess crying intensity, frequency, duration of crying and pain related behaviour throughout the day in six hour periods. Results Light needling resulted in a significant reduction in the rated crying intensity (assessed by a numeric rating scale, 0 to 10). For example, during the morning time period 0600–1200 hours, the median (range) rated crying intensity changed from 6 (1 to 9) pre-treatment to 2 (0 to 5) post-treatment (P=0.002), in the light needling group. The corresponding ratings for the children in the control group was 6 (0 to 10) and 5 (0 to 10) respectively. The difference between the groups was significant (P=0.016). There were also significant differences between the groups for the afternoon (1200–1800 hours), and evening (1800–midnight) time periods. Pain related behaviour like facial expression, was also significantly less pronounced in the light needling group as compared to the control group post-treatment, (P=0.027). The parents rated the light needling as more effective in improving symptoms than the control group (P<0.001). Conclusion Four treatments with light needling on one point in the hand may alleviate crying and pain related behaviour without any noted side effects.
Neuropathic Pain: A New Theory for Chronic Pain of Intrinsic Origin
Authors: Gunn C Chan 
Published: April 2009

Why is acupuncture accepted in the East, especially for the treatment of chronic pain, but not in the West? One reason is that the modus operandi of acupuncture is not fully understood; another is the enigmatic nature of chronic pain. This article introduces a new concept of chronic pain, and suggests how acupuncture may relieve it. Chronic pain may arise from sources that are extrinsic to the nervous system (for example, ongoing injury or inflammation), but it can also be intrinsic and the result of abnormal hypersensitivity (supersensitivity) in neuropathic or partially denervated structures. Neuropathic pain typically affects the musculoskeletal system, and a pivotal component of this type of pain is muscle spasm or shortening. Spasm can cause pain localised to muscle, but sustained muscle spasm or shortening mechanically overloads tendons and their attachments, and can produce pain in these structures. Since neuropathic pain is different from nociception or inflammation, its treatment is also distinct (desensitisation of supersensitivity). Most physical treatment modalities for this type of pain, such as heat, massage or transcutaneous electrical nerve stimulation (TENS), desensitise by reflex stimulation of the affected part via its intact innervation. However these modalities are passive and limited in scope. Stimulation ends when their application is terminated. In contrast, injection techniques, including acupuncture, are more effective and long-lasting, because the tissue injury that they produce can unleash the body's healing source of bioenergy through the current of injury. Tissue injury also releases the platelet-derived growth factor (PDGF), which can promote healing.
Estrogens and Human Papilloma Virus Oncogenes Regulate Human Ether-à-go-go-1 Potassium Channel Expression
Authors: Díaz Lorenza , Ceja-Ochoa Irais , Restrepo-Angulo Iván , Larrea Fernando , Avila-Chávez Euclides , García-Becerra Rocío , Borja-Cacho Elizabeth , Barrera David , Ahumada Elías , Gariglio Patricio , Alvarez-Rios Elizabeth , Ocadiz-Delgado Rodolfo , Garcia-Villa Enrique , Hernández-Gallegos Elizabeth , Camacho-Arroyo Ignacio , Morales Angélica , Ordaz-Rosado David , García-Latorre Ethel , Escamilla Juan , Sánchez-Peña Luz Carmen , Saqui-Salces Milena , Gamboa-Dominguez Armando , Vera Eunice , Uribe-Ramírez Marisela , Murbartián Janet , Ortiz Cindy Sharon , Rivera-Guevara Claudia , De Vizcaya-Ruiz Andrea , Camacho Javier 
Published: April 2009

Abstract
Ether-à-go-go-1 (Eag1) potassium channels are potential tools for detection and therapy of numerous cancers. Here, we show human Eag1 (hEag1) regulation by cancer-associated factors. We studied hEag1 gene expression and its regulation by estradiol, antiestrogens, and human papillomavirus (HPV) oncogenes (E6/E7). Primary cultures from normal placentas and cervical cancer tissues; tumor cell lines from cervix, choriocarcinoma, keratinocytes, and lung; and normal cell lines from vascular endothelium, keratinocytes, and lung were used. Reverse transcription-PCR (RT-PCR) experiments and Southern blot analysis showed Eag1 expression in all of the cancer cell types, normal trophoblasts, and vascular endothelium, in contrast to normal keratinocytes and lung cells. Estradiol and antiestrogens regulated Eag1 in a cell type–dependent manner. Real-time RT-PCR experiments in HeLa cells showed that Eag1 estrogenic regulation was strongly associated with the expression of estrogen receptor-α. Eag1 protein was detected by monoclonal antibodies in normal placenta and placental blood vessels. Patch-clamp recordings in normal trophoblasts treated with estradiol exhibited potassium currents resembling Eag1 channel activity. Eag1 gene expression in keratinocytes depended either on cellular immortalization or the presence of HPV oncogenes. Eag1 protein was found in keratinocytes transfected with E6/E7 HPV oncogenes. Cell proliferation of E6/E7 keratinocytes was decreased by Eag1 antibodies inhibiting channel activity and by the nonspecific Eag1 inhibitors imipramine and astemizole; the latter also increased apoptosis. Our results propose novel oncogenic mechanisms of estrogen/antiestrogen use and HPV infection. We also suggest Eag1 as an early indicator of cell proliferation leading to malignancies and a therapeutic target at early stages of cellular hyperproliferation. [Cancer Res 2009;69(8):3300–7]
Identification of a Biphasic Role for Genistein in the Regulation of Prostate Cancer Growth and Metastasis
Authors: El Touny Lara H. , Banerjee Partha P. 
Published: April 2009

Abstract
Considered a chemopreventive agent, the ability of genistein to modulate the progression of existing prostate cancer (CaP) is not clear. We show here that the consumption of genistein (250 mg/kg diet) by 12-week-old transgenic adenocarcinoma mouse prostate (TRAMP-FVB) mice harboring prostatic intraepithelial neoplasia lesions until 20 weeks of age induces an aggressive progression of CaP, as evidenced by a 16% increase in the number of well-differentiated and poorly differentiated prostates, coinciding with a 70% incidence of pelvic lymph node (LN) metastases as opposed to 0% and 10% in 0 and 1,000 mg/kg groups, concomitant with elevated osteopontin (OPN) expression in prostates and LNs. Equivalent nanomolar (500 nmol/L) concentrations of genistein recapitulated these effects in human PC3 CaP cells as evidenced by increased proliferation, invasion, and matrix metalloproteinase-9 (MMP-9) activity (∼2-fold), accompanied by an up-regulation of OPN expression and secretion, compared with vehicle-treated cells. A pharmacologic dose (50 μmol/L) decreased proliferation, invasion, and MMP-9 activity (&gt;2.0-fold) concomitant with OPN reduction. Upon OPN knockdown by short hairpin RNA, genistein was no longer effective in up-regulating PC3 cell proliferation, invasion, and MMP-9 activation, which were significantly reduced in the absence of OPN, highlighting the requirement for OPN in mediating the effects of genistein. Proliferation, invasion, and OPN levels were also nonsignificantly induced by genistein in the presence of ICI 182,780 or wortmannin, indicating a dependence on phosphatidylinositol 3-kinase and estrogen signaling. Our results suggest the presence of a biphasic regulation of CaP growth and metastasis by genistein, warranting careful examination of the effects of genistein on hormone-dependent cancers in a chemotherapeutic setting. [Cancer Res 2009;69(8):3695–703]
Tripeptidyl Peptidase II Plays a Role in the Radiation Response of Selected Primary Cell Types but not Based on Nuclear Translocation and p53 Stabilization
Authors: Firat Elke , Tsurumi Chizuko , Gaedicke Simone , Huai Jisen , Niedermann Gabriele 
Published: April 2009

Abstract
The giant cytosolic protease tripeptidyl peptidase II (TPPII) was recently proposed to play a role in the DNA damage response. Shown were nuclear translocation of TPPII after γ-irradiation, lack of radiation-induced p53 stabilization in TPPII-siRNA–treated cells, and complete tumor regression in mice after γ-irradiation when combined with TPPII-siRNA silencing or a protease inhibitor reported to inhibit TPPII. This suggested that TPPII could be a novel target for tumor radiosensitization and prompted us to study radiation responses using TPPII-knockout mice. Neither the sensitivity to total body irradiation nor the radiosensitivity of resting lymphoid cells, which both strongly depend on p53, was altered in the absence of TPPII. Functional integrity of p53 in TPPII-knockout cells is further shown by a proper G1 arrest and by the accumulation of p53 and its transcriptional targets, p21, Bax, and Fas, on γ-irradiation. Furthermore, we could not confirm radiation-induced nuclear translocation of TPPII. Nevertheless, after γ-irradiation, we found slightly increased mitotic catastrophe of TPPII-deficient primary fibroblasts and increased apoptosis of TPPII-deficient activated CD8+ T cells. The latter was accompanied by delayed resolution of the DNA double-strand break marker γH2AX. This could, however, be due to increased apoptotic DNA damage rather than reduced DNA damage repair. Our data do not confirm a role for TPPII in the DNA damage response based on nuclear TPPII translocation and p53 stabilization but nevertheless do show increased radiation-induced cell death of selected nontransformed cell types in the absence of the TPPII protease. [Cancer Res 2009;69(8):3325–31]
K858, a Novel Inhibitor of Mitotic Kinesin Eg5 and Antitumor Agent, Induces Cell Death in Cancer Cells
Authors: Nakai Ryuichiro , Iida Shin-ichi , Takahashi Takeshi , Tsujita Tetsuya , Okamoto Seiho , Takada Chie , Akasaka Kazuhito , Ichikawa Shunji , Ishida Hiroyuki , Kusaka Hideaki , Akinaga Shiro , Murakata Chikara , Honda Shinobu , Nitta Masayuki , Saya Hideyuki , Yamashita Yoshinori 
Published: April 2009

Abstract
The aim of this study was to investigate the mechanism of inhibition of Eg5 (kinesin spindle protein), a mitotic kinesin that plays an essential role in establishing mitotic spindle bipolarity, by the novel small molecule inhibitor K858. K858 was selected in a phenotype-based forward chemical genetics screen as an antimitotic agent, and subsequently characterized as an inhibitor of Eg5. K858 blocked centrosome separation, activated the spindle checkpoint, and induced mitotic arrest in cells accompanied by the formation of monopolar spindles. Long-term continuous treatment of cancer cells with K858 resulted in antiproliferative effects through the induction of mitotic cell death, and polyploidization followed by senescence. In contrast, treatment of nontransformed cells with K858 resulted in mitotic slippage without cell death, and cell cycle arrest in G1 phase in a tetraploid state. In contrast to paclitaxel, K858 did not induce the formation of micronuclei in either cancer or nontransformed cells, suggesting that K858 has minimal effects on abnormalities in the number and structure of chromosomes. K858 exhibited potent antitumor activity in xenograft models of cancer, and induced the accumulation of mitotic cells with monopolar spindles in tumor tissues. Importantly, K858, unlike antimicrotubule agents, had no effect on microtubule polymerization in cell-free and cell-based assays, and was not neurotoxic in a motor coordination test in mice. Taken together, the Eg5 inhibitor K858 represents an important compound for further investigation as a novel anticancer therapeutic. [Cancer Res 2009;69(9):3901–9]
Oncogenic Kras Requires Simultaneous PI3K Signaling to Induce ERK Activation and Transform Thyroid Epithelial Cells In vivo
Authors: Miller Kelly A. , Yeager Nicole , Baker Kristen , Liao Xiao-Hui , Refetoff Samuel , Di Cristofano Antonio 
Published: April 2009

Abstract
Thyroid tumors arising from the follicular cells often harbor mutations leading to the constitutive activation of the PI3K and Ras signaling cascades. However, it is still unclear what their respective contribution to the neoplastic process is, as well as to what extent they interact. We have used mice harboring a Kras oncogenic mutation and a Pten deletion targeted to the thyroid epithelium to address in vivo these questions. Here, we show that although each of these two pathways, alone, is unable to transform thyroid follicular cells, their simultaneous activation is highly oncogenic, leading to invasive and metastatic follicular carcinomas. In particular, phosphatidylinositol-3-kinase (PI3K) activation suppressed Kras-initiated feedback signals that uncouple mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) and ERK activation, thus stunting MAPK activity; in addition, PI3K and Kras cooperated to drastically up-regulate cyclin D1 mRNA levels. Finally, combined pharmacologic inhibition of PI3K and MAPK completely inhibited the growth of double-mutant cancer cell lines, providing a compelling rationale for the dual targeting of these pathways in thyroid cancer. [Cancer Res 2009;69(8):3689–94]