Clinical evaluation of sizofiran combined with irradiation in patients with cervical cancer

Following a previous report [1] we ascertained the effectiveness of sizofiran (Schizophyllan:SPG) to prolong the survival and time to recurrence of the patients with Stage II or III cervical cancer, as evaluated in a 5-year randomized controlled study conducted in 19 institutions in Japan. Of the overall patients with Stage II or III cancer, time to recurrence and survival rate in the group on SPG were significantly longer than in the control group. In the Stage II patients, there was significant difference in time to recurrence, and survival of SPG group tended to be longer than that of the control group. However, in the Stage III patients, there was no significant difference in either time to recurrence or survival rate.     

Improvement of long-term prognosis in patients with ovarian cancers by adjuvant sizofiran immunotherapy: a prospective randomized controlled study

The effect of immunotherapy using sizofiran (SPG) on the prognosis of patients with ovarian cancers was prospectively studied in a total of 68 patients, who were randomly assigned to either a cisplatin, adriamycin and cyclophosphamide (PAC) therapy group or a PAC plus SPG combination therapy group.The survival rate was significantly higher in patients with stage Ic, II or III cancers treated with the PAC plus SPG combination, compared with the patients treated with PAC alone. In the SPG-receiving patients with stage Ic or more advanced cancers who were treated with four cycles or more of PAC, the outcome was improved (Cox-Mantel, p=0.074; generalized Kruskal-Wallis, p=0.032). Similar improvement was also observed in the patients with non-serous adenocarcinomas (Cox-Mantel, p-0.076; generalized Krukal-Wallis, p=0.045). No side effects attributable to SPG were recorded.The present results suggest that the use of SPG in combination with long-term chemotherapy improves the postoperative prognosis in ovarian cancer patients.Abbreviations SPG sizofiran     

Effectiveness of a call/recall system in improving compliance with cervical cancer screening: a randomized controlled trial

OBJECTIVE: To determine the effectiveness of a simple call/recall system in improving compliance with cervical cancer screening among women not screened in the previous 3 years. DESIGN: Prospective randomized controlled study. SETTING: Two family medicine clinics (1 urban, 1 rural) affiliated with Memorial University of Newfoundland, St. John''s. PARTICIPANTS: A sample of women aged 18-69 years who were listed as patients of the clinics but who had not had a Papanicolaou test (Pap test) within the 3 years before the start of the study. Of 9071 women listed as patients 1360 (15.0%) had not undergone screening in the previous 3 years. A random sample of 650 were selected, 209 of whom were excluded because they had had a hysterectomy, had had a recent Pap test, had moved or had records containing clerical errors. This left 441 women for the study. INTERVENTION: The 221 women in the intervention group were sent a letter asking them to seek a Pap test and a reminder letter 4 weeks later. The 220 in the control group were sent no letters. MAIN OUTCOME MEASURES: Number of women who had a Pap test within 2 months and 6 months after the first letter was sent. RESULTS: Within 2 months, more women in the intervention group than in the control group had been screened (2.8% [5/178] and 1.9% (4/208] respectively). There was also a difference between the overall proportions at 6 months (10.7% [19/178] and 6.3% [13/208] respectively). None of the differences was statistically significant. CONCLUSION: A letter of invitation is not sufficient to encourage women who have never or have infrequently undergone a Pap test to come in for cervical cancer screening. The effectiveness of added recruitment methods such as opportunistic screening by physicians, follow-up by telephone and the offer of a specific appointment should be evaluated.     

Effect of sizofiran on regional lymph nodes in patients with head and neck cancer

The immunomodulating effects of preoperative sizofiran (SPG) administration on regional lymph nodes were studied in patients with stage III or IV head and neck cancer, by comparing the immunofunction of peripheral blood. The regional lymph nodes were dissected surgically, and freshly obtained mononuclear cells were studied to investigate the interleukin-2 (IL-2) production, the LAK and NK activities, and the quantitative analysis of the surface phenotype of the mononuclear cells. The results indicated that SPG enhanced immunological activities in the regional lymph nodes, as shown by increased IL-2 production and cytotoxic activities of the effector cells (NK, LAK), and increased helper T lymphocytes (CD4⁺) in the tumor-uninvolved lymph nodes. The immunofunction following SPG administration was attenuated, but was still augmented in the regional lymph nodes with metastases. Therefore, SPG was found to be a biologic response modifier to enhance the immunofunctions of the regional lymph node in patients with head and neck cancer.     

Clinical management of patients with invasive cervical cancer following a negative Pap smear

Among 535 patients with invasive cervical carcinoma seen between January 1975 and June 1986, 26 were found to have developed the disease within six months (65 percent), 35 within 12 months (88 percent), 37 within 13 months (93 percent), and three developed the disease within 17 months after a negative Pap smear. Eighty-eight percent of these 40 patients were under age 40 at diagnosis. Rapidly progressive cancers are highly resistant to radiation therapy. Seven stage IB patients treated only with radiation died within nine to 29 months after initial therapy. By contrast, 15 patients treated by radical hysterectomy and four by radical hysterectomy and post-surgical radiation were alive with no evidence of disease from six to 109 months after surgery (median, 30 months). Six of nine patients with stage II to IV disease treated with radiation have died; the remaining three are alive. One patient is well 14 months after therapy, but two others have developed metastases seven and 12 months after treatment. Surprisingly, 37 of 40 patients had symptoms of pain, bleeding, and discharge at the initial diagnosis, but their physicians had a false sense of security because of a recent negative Pap smear. Early biopsy diagnosis and radical hysterectomy with bilateral pelvic lymphadenectomy is the most effective management for this cancer.     

Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial

The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight. These findings warrant further investigation.     

Magnetic field therapy in patients with cytostatics‐induced polyneuropathy: A prospective randomized placebo‐controlled phase‐III study

No causal treatment for chemotherapy‐induced peripheral neuropathy (CIPN) is known. Therefore, there is an urgent need to develop a therapy for CIPN. Only scarce clinical data are available concerning magnetic field therapy (MFT) in this context. We conducted a unicentric, randomized, double‐blind, placebo‐controlled phase‐III trial of an MFT device versus placebo. In this study, we randomized 44 patients with CIPN to two treatment groups, where 21 patients were treated with MFT (Group 1) and 23 patients received placebo (Group 2). We evaluated the efficacy of MFT at baseline (T₁), after 3 weeks of study treatment (T₂), and after 3 months of study treatment (T₃). The primary endpoint was nerve conduction velocity (NCV), while secondary endpoints were the Common Toxicity Criteria (CTCAE) score and the Pain Detect End Score at T₃. Seventeen of the patients in Group 1 and 14 patients in Group 2 completed the respective study treatment. The primary endpoint, significant improvement of NCV at T₃, was achieved by MFT (P = 0.015), particularly for sensory neurotoxicity of the peroneal nerve. Also, in respect to the secondary endpoints, significant improvement (P = 0.04) was achieved in terms of the patients’ subjectively perceived neurotoxicity (CTCAE score), but not of neuropathic pain (P = 0.11). From data in the randomized study presented here, a positive effect on the reduction of neurotoxicity can be assumed for the MFT device. Patients with sensory neurotoxicity in the lower limbs, especially, should therefore be offered this therapy. Bioelectromagnetics. 38:85–94, 2017. © 2016 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc.     

Clinical effectiveness and safety of salvia miltiorrhiza depside salt combined with aspirin in patients with stable angina pectoris: A multicenter,pragmatic, randomized controlled trial

BackgroundSalvia Miltiorrhiza Depside Salt (SMDS) was extracted from Salvia miltiorrhiza with high-quality control of active principles. In 2005, China's FDA approved the use of SMDS for stable angina pectoris (SAP), but the evidence of SMDS combined with aspirin remains unclear.PurposeThe aim of this study was to assess the clinical effectiveness and safety of SMDS combined with aspirin in patients with SAP.MethodsA multicenter, pragmatic, three-armed parallel group and an individually randomized controlled superiority trial was designed. Participants aged 35 to 75 years old with SAP were recruited from four "Class Ⅲ Grade A" hospitals in China. Participants who were randomized into the SMDS group were treated with SMDS by intravenous drip. Participants in the control group received aspirin enteric-coated tablets (aspirin). Participants who were randomly assigned to the combination group received SMDS combined with aspirin. All participants received standard care from clinicians, without any restrictions. The primary outcome measure was thromboelastography (TEG). Secondary outcome measures included symptom score of the Seattle Angina Questionnaire (SAQ), visual analogue scale (VAS) score of traditional Chinese medicine (TCM) symptoms, platelet aggregation measured by light transmittance aggregometry (LTA), and fasting blood glucose. Effectiveness evaluation data were collected at baseline and ten days after treatment. Researchers followed up with participants for one month after treatment to determine whether adverse events (AEs) or adverse drug reactions (ADRs) such as bleeding tendency occurred. All statistical calculations were carried out with R 3.5.3 statistical analysis software.ResultsA total of 135 participants completed follow-up data on the primary outcome after ten days of treatment. Participants in the SMDS combined aspirin group had the highest improvement rate of sensitivity in AA% [p < 0.001, 95% CI (0.00–0.00)], from 30.6% before treatment to 81.6% after treatment. Participants with drug resistance (AA% < 20%) in the SMDS combined with aspirin group also had the highest sensitivity rate [p < 0.001, 95% CI (0.00–0.00)] after treatment (accounting for 81.0% of the combination group and 60.7% of the sensitive participants). The improvement of TCM symptoms in participants treated with SMDS combined with aspirin was significantly better than that of the aspirin group [MD = 1.71, 95% CI (0.15–3.27), p = 0.032]. There were no significant differences in other indexes (R, TPI, MA, K, CI, α value) of TEG, SAQ, platelet aggregation and fasting blood glucose among the three groups. No bleeding tendency or ADRs occurred in all participants.ConclusionSMDS combined with aspirin is a clinically effective and safe intervention to treat adults aged 35 and older with SAP. This trial shows that SMDS combined with aspirin can significantly improve the sensitivity rate of AA% in TEG and the VAS score of TCM symptoms. Further large samples and high-quality research are needed to determine if certain participants might benefit more from SMDS combined with aspirin. The study protocol was registered in the Clinical Trials USA registry (registration No. NCT02694848).     

Antihypertensive medications and survival in patients with cancer: A population-based retrospective cohort study

Background: The association between antihypertensive medications and survival in cancer patients remains unclear. Objectives: To explore the association between classes of antihypertensive drugs and survival in cancer patients. Methods: Provincial Cancer Registry data was linked with a Provincial Drug Program Information Network (DPIN) for patients with lung (n = 4241), colorectal (n = 3967), breast (n = 4019) or prostate (n = 3355) cancer between the years of 2004 and 2008. Cox regression analyses were used to compare survival of patients using beta blockers (BBs), angiotensin-converting enzyme inhibitors/receptor blockers (ACEi/ARB), calcium channel blockers (CCBs) or thiazide diuretics (TDs) to survival of patients who did not use any of these antihypertensive drugs. Survival of patients using only one class of antihypertensive drugs were compared to each other, with BBs as the reference class. Results: Compared to the antihypertensive drug non-user cohort, BBs had no effect on survival for any of the cancers. ACEi/ARBs use was weakly associated with increased deaths for breast cancer (HR: 1.22, 95% CI: 1.04–1.44) and lung cancer (HR: 1.11, 95% CI: 1.03–1.21) patients. Deaths were also increased with CCB use in patients with breast cancer (HR: 1.22, 95% CI: 1.02–1.47) and with TD use in lung cancer patients (HR: 1.1, 95% CI: 1.01–1.19). There was strong evidence (p-value <0.0001) of an increase in deaths with TD use for colorectal (HR: 1.28, 95% CI: 1.15–1.42), and prostate (HR 1.41, 1.2–1.65) cancer patients. When including only antihypertensive drug users prescribed one drug class, lung cancer patients receiving CCBs had improved survival compared to BBs (HR 0.79, 95% CI: 0.64–0.98). Conclusions: Some classes of antihypertensive agents are associated with a decreased survival in certain cancers. The decrease could be due to more comorbidities in antihypertensive drug users. However, CCB use was associated with improved survival in lung cancer patients.     

Inhibitory effect of metastasis by combined administration with interleukin-2 and sizofiran,a single glucan — immunohistochemical study —

Innovations in methods of combined administration with other BRM or chemotherapeutic drugs have been discussed. We have reported [1] that combined administration with recombinant interleukin-2 (rIL-2) and sizofiran (SPG) is effective in prolonging survival time of C57BL/6 mice intraperitoneally inoculated with EL-4 lymphoma. The immunomechanisms of the combined administration were clarified investigating the intraperitoneal cell population in the primary tumor site, especially the tumor infiltrating lymphocyte (TIL) quantitatively. In the present study, to clarify the antitumor effects of combined administration with rIL-2 and SPG on the metastatic sites, the immnunomechanisms of the suppressive effects of combined administration on the metastasis were studied in EL-4 lymphoma cells intraperitoneally transplanted to mice. Inasmuch as EL-4 lymphoma shows rapid hepatosplenic metastasis, we studied the metastatic foci in the liver and the spleen semiquantitatively investigating the histopathological and immunohistochemical findings of the metastatic foci, especially the TIL. The metastatic foci were stained by hematoxylin-eosin (HE) and monoclonal antibodies (L3T4, Lyt2, asialo GM1, Mac-1, and Ia). The combined administration resulted in: 1) fewer infiltrating tumor cells, 2) more lymphocytic infiltration, and 3) more antitumor effector cells (cytotoxic T cells: Lyt2 and natural killer cells: asialo GM1), macrophages (Mac-1), helper T cells (L3T4), and cells with MHC-class-II antigen (Ia) than did administration of rIL-2 alone or SPG alone, or no administration of these two at all. Combined administration with rIL-2 and SPG appears to activate antitumor-immune response at the metastatic site more effectively than when either agent is administered alone.     

Long-term survival of patients with breast cancer: a study of the curability of the disease.

A retrospective analysis was made of 3878 cases of breast carcinoma first seen in Edinburgh from 1954 to 1964. During this time there was a policy to treat breast cancer by simple mastectomy and x-ray therapy, and over 90% of cases classified as international stages I and II were so treated. The mortality in these women was compared with that in an equivalent normal population using Scottish national age-specific death rates. For every year of follow-up within 20 years of initial treatment there was an excess mortality from all causes. There was an overall excess mortality of 58% among patients with breast cancer 15-20 years after initial treatment, and 20 times more deaths occurred in this period from breast cancer than in a normal population. For patients disease-free after 15 years there was still a 28% excess mortality from all causes. Factors known to be of major prognostic significance for five-year survivorship had less influence than might have been expected when the ratio of observed to expected deaths was considered for longer periods of follow-up. The effect of clinical staging (I, II, or III), though initially marked, largely disappeared by the 10th year of follow-up, and after allowing for age there was no evidence beyond 10 years of an effect on survival of the original stage of the disease. Similarly, the effect of tumour size on survival disappeared after 10 years. Women who were premenopausal at presentation still had a significant excess of deaths in the fourth quinquennium of follow-up. In the menopausal and postmenopausal groups combined there was still a small non-significant excess of deaths from all causes after 15 years but this almost disappeared when patients who had already relapsed were excluded. In terms of overall mortality only patients who have undergone the menopause before presentation and who are disease-free 15 years after primary treatment may prove to be cured by conventional techniques such as simple mastectomy and postoperative radiotherapy.     

爱杰特联合波姆光治疗宫颈糜烂的临床研究

目的:探讨爱杰特联合波姆光治疗宫颈糜烂的疗效。方法:将300例宫颈糜烂患者,随机分为A组:爱杰特治疗;B组:波姆光治疗;C组:爱杰特联合波姆光治疗。分别于术后1个月及3个月复查观察疗效。结果:A、B、C三组的总有效率分别为88.67%、88%、98-33%,C组的有效率显著高于A组及B组(P<0.01)。结论:波姆光与爱杰特联合治疗宫颈糜烂的有效率高、操作简单、是宫颈糜烂的一种理想治疗方法,值得临床推广应用。     

Long-term survival of patients with prostate cancer in Martinique: Results of a population-based study

BackgroundMartinique has one of the highest incidences of prostate cancer (PCa) worldwide. We analysed overall survival (OS) among patients with PCa in Martinique, using data from a population-based cancer registry between 2005 and 2014.MethodsThe log-rank test was used to assess the statistical differences between survival curves according to age at diagnosis, risk of disease progression including Gleason score, stage at diagnosis and Prostate Specific Antigen (PSA). A multivariable Cox model was constructed to identify independent prognostic factors for OS.ResultsA total of 5045 patients were included with a mean age at diagnosis of 68.1±9.0 years [36.0 – 98.0 years]. Clinical stage was analysed in 4999 (99.1% of overall), 19.5% were at low risk, 34.7% intermediate and 36.9% at high risk. In our study, 8.9% of patients with available stage at diagnosis, were regional/metastatic cancers. Median PSA level at diagnosis was 10.4 ng/mL. High-risk PCa was more frequent in patients aged 65-74 and ≥75 years as compared to those aged <65 years (36.6% and 48.8% versus 28.7% respectively; p<0.0001). One-year OS was 96.3%, 5-year OS was 83.4 and 10-year OS was 65.0%. Median survival was not reached in the whole cohort. High-risk PCa (HR=2.32; p<0.0001), regional/metastatic stage (HR= 9.51; p<0.0001) and older age (65-74 and ≥75 years - respectively HR=1.70; and HR=3.38), were independent prognostic factors for OS (p<0.0001).ConclusionThis study provides long term data that may be useful in making cancer management decisions for patients with PCa in Martinique.     

Dosimetric study of a hybrid plan technique for external beam radiotherapy in patients with cervical cancer

The aim of this study was to investigate the effect of a hybrid technique which results from combining intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) for the treatment of cervical cancer patients. Plans made with the hybrid technique and pure IMRT and VMAT were retrospectively compared in 20 patients with cervical cancer at different stages. All plans were made using the same contours based on the original computed tomography (CT) scans. Conformity (CI) and homogeneity (HI) indices of the planning target volumes (PTVs) were calculated for each technique in order to evaluate plan quality. All techniques were compared in terms of dose to organs at risk (OARs), number of monitor units (MUs) and treatment time. It turned out that plans made with the hybrid technique had improved dose conformity and homogeneity compared to plans made only with IMRT and VMAT (p < 0.001). Regarding the OARs, the maximum dose (D_max) delivered to the bladder, rectum and femoral heads was lower for the hybrid plans compared to the IMRT and VMAT plans (p < 0.001). The volumes irradiated to doses of 50 Gy (V_50Gy) for rectum, bladder and bowel were lower for the hybrid plans (p < 0.001, p = 0.002). Furthermore, the treatment time and MU values for the hybrid plans were found to be between of the values for the IMRT and VMAT plans. It is concluded that, as compared to IMRT and VMAT plans, the hybrid plan technique allowed a better conformity and homogeneity for the dose distribution in the PTV and a dose reduction to the OARs.

     

Clinical effects of intrathecal administration of expanded Wharton jelly mesenchymal stromal cells in patients with chronic complete spinal cord injury: a randomized controlled study

Background aimsSpinal cord injury (SCI) represents a devastating condition leading to severe disability related to motor, sensory and autonomic dysfunction. Stem cell transplantation is considered a potential emerging therapy to stimulate neuroplastic and neuroregenerative processes after SCI. In this clinical trial, the authors investigated the safety and clinical recovery effects of intrathecal infusion of expanded Wharton jelly mesenchymal stromal cells (WJ-MSCs) in chronic complete SCI patients.MethodsThe authors designed a randomized, double-blind, crossover, placebo-controlled, phase 1/2a clinical trial (NCT03003364). Participants were 10 patients (7 males, 3 females, age range, 25–47 years) with chronic complete SCI (American Spinal Injury Association A) at dorsal level (T3-11). Patients were randomly assigned to receive a single dose of intrathecal ex vivo-expanded WJ-MSCs (10 × 10⁶ cells) from human umbilical cord or placebo and were then switched to the other arm at 6 months. Clinical evaluation (American Spinal Injury Association impairment scale motor and sensory score, spasticity, neuropathic pain, electrical perception and pain thresholds), lower limb motor evoked potentials (MEPs) and sensory evoked potentials (SEPs), Spinal Cord Independence Measure and World Health Organization Quality of Life Brief Version were assessed at baseline, 1 month, 3 months and 6 months after each intervention. Urodynamic studies and urinary-specific quality of life (Qualiveen questionnaire) as well as anorectal manometry, functional assessment of bowel dysfunction (Rome III diagnostic questionnaire) and severity of fecal incontinence (Wexner score) were conducted at baseline and at 6 months after each intervention.ResultsIntrathecal transplantation of WJ-MSCs was considered safe, with no significant side effects. Following MSC infusion, the authors found significant improvement in pinprick sensation in the dermatomes below the level of injury compared with placebo. Other clinically relevant effects, such as an increase in bladder maximum capacity and compliance and a decrease in bladder neurogenic hyperactivity and external sphincter dyssynergy, were observed only at the individual level. No changes in motor function, spasticity, MEPs, SEPs, bowel function, quality of life or independence measures were observed.ConclusionsIntrathecal transplantation of human umbilical cord-derived WJ-MSCs is a safe intervention. A single intrathecal infusion of WJ-MSCs in patients with chronic complete SCI induced sensory improvement in the segments adjacent to the injury site.     

High-intensity aerobic interval training and resistance training are feasible in rectal cancer patients undergoing chemoradiotherapy: a feasibility randomized controlled study

BackgroundThere has been growing evidence of the benefits of high-intensity aerobic interval training (HIIT) and resistance training (RES) for populations with cancer. However, these two modalities have not yet been performed alone in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (NACR T). Therefore, this study aimed to determine the feasibility of HIIT and RES in rectal cancer patients undergoing NACR T.Materials and methodsRectal cancer patients set to undergo NACRT were randomly assigned to HIIT intervention, RES intervention, or the usual care. Feasibility of HIIT and RES was assessed by measuring recruitment rate, adherence (retention rate, attendance rate, and exercise sessions duration and intensity), and adverse events. Endpoints (changes in fatigue, health-related quality of life, depression, daytime sleepiness, insomnia, sleep quality, functional exercise capacity, and executive function) were assessed at baseline and at week 5.ResultsAmong the 20 eligible patients, 18 subjects were enrolled and completed the study, yielding a 90% recruitment rate and 100% retention rate. Attendance at exercise sessions was excellent, with 92% in HIIT and 88% in RES. No exercise-related adverse events occurred.ConclusionThis study demonstrated that HIIT and RES are feasible in rectal cancer patients undergoing NACR T.Trial registrationwww.clinicaltrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT03252821","term_id":"NCT03252821"}}NCT03252821 (date of registration: March 30, 2017)     

A randomized, controlled dose response study of intravenous sodium diethyldithiocarbamate in patients with advanced human immunodeficiency virus infection

Sodium diethyldithiocarbamate (Imuthiol, DTC) has previously been observed to promote T-cell maturation in animal models and to reduce lymphadenopathy and improve survival in a murine AIDS model. In addition, several clinical studies have suggested that one dosage regimen may be active in patients with HIV infection. We conducted a randomized, controlled dose response study of intravenous DTC in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). Drug associated toxicities included gastrointestinal upset, burning at the infusion site, metallic taste, sneezing, confusional states, hyperactivity, delusional thinking, and myoclonus. Toxicity was ameliorated by dose reduction. The maximally tolerated dose varied for individual patients from 200 mg/m2 weekly to 800 mg/m2 twice weekly. No myelosuppression was observed. In patients with greater than 200 CD4+ cells/uL, a statistically significant reduction of lymphadenopathy occurred; whereas no beneficial effects were observed in patients with less than 200 CD4+ cells/uL. Improvement in symptom score and stabilization of CD4+ count also occurred in the treated group, although these trends did not reach statistical significance. Further controlled clinical trials of DTC in earlier HIV infection are warranted.     

Effect of oriental medicine music therapy on patients with Hwa-byung: a study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: Hwa-byung, a Korean culture-bound syndrome with both psychological and somatic symptoms, is also known as 'anger syndrome'. It includes various physical symptoms including anxiety, a feeling of overheating, a sensation of pressure on the chest, heart palpitations, respiratory stuffiness, insomnia, and anxiety.Methods/designThe proposed study is a single-center, double-blind, randomized, controlled trial with two parallel arms: an oriental medicine music therapy (OMMT) group and a control music therapy (CMT) group. In total, 18 patients will be enrolled into the trial. The first visit will be the screening visit. At baseline (visit 2), all participants fulfilling both the inclusion and the exclusion criteria will be split and randomly divided into two equal groups: the OMMT and the CMT (n = 24 each). Each group will receive treatment sessions over the course of 4 weeks, twice per week, for eight sessions in total. The primary outcome is the State-Trait Anxiety Inventory (STAI), and the secondary outcomes are the Hwa-byung scale (H-scale), the Center for Epidemiologic Studies Depression Scale (CES-D), the Hwa-byung visual analogue scale (H-VAS) for primary symptoms, the World Health Organization Quality of Life scale, brief version (WHOQOL-BREF), and levels of salivary cortisol. Patients will be asked to complete questionnaires at the baseline visit (visit 2), after the last treatment session (visit 9), and at 4 weeks after the end of all trial sessions (visit 10). From the baseline (visit 2) through the follow-up (visit 10), the entire process will take a total of 53 days. DISCUSSION: This proposed study targets patients with Hwa-byung, especially those who have exhibited symptoms of anxiety. Therefore, the primary outcome is set to measure the level of anxiety. OMMT is music therapy combined with traditional Korean medicinal theories. Unlike previously reported music therapies, for which patients simply listen to music passively, in OMMT, patients actively move their bodies and play the music. Because Hwa-byung is caused by an accumulation of blocked emotions and anger inside the body, OMMT, because of its active component, is expected to be more efficacious than pre-existing music therapies.Trial registrationCurrent Controlled Trials ISRCTN11939282.     

A randomized multicenter study of optimal circadian time of vinorelbine combined with chronomodulated 5-fluorouracil in pretreated metastatic breast cancer patients: EORTC trial 05971

Studies in animals synchronized with an alternation of 12 h of light and 12 h of darkness have showed that hematological and systemic toxicities could be reduced if vinorelbine were administered 19 or 23 hours after light onset (HALO), corresponding to 17:00 and 21:00 h in diurnally active humans. This trial aimed to define the least toxic time of vinorelbine administration in metastatic breast cancer patients. Initially, the study treatment consisted of three courses of vinorelbine of 30 mg/m(2)/d on D1 and D6 and chronomodulated 5-fluorouracil of 850 mg/m(2) from D2 to D5 every 21 days. Ninety metastatic breast cancer patients were randomized to receive vinorelbine at one of the eight possible dosing times. Further to the recommendations of the Independent Data Monitoring Committee, the vinorelbine dose was reduced to 25 mg/m(2)/d midway through the study. The primary objective of the study was detection of the least toxic time based on the incidence of grade 3-4 (G3-4) neutropenia. To show a significant result, the 90% confidence interval width of the least toxic time had to be<6 h. The least toxic time detection based on the incidence of other toxicities was also analyzed. The time of least drug toxic was estimated using a logistic regression model assuming that the logit transformation of the toxicity rate follows a sinusoidal distribution over 24 h. The bootstrap technique was used to obtain the 90% confidence interval. The least toxic time of G3-4 neutropenia was observed at 21:00 h with a non-significant 90% CI. Secondary endpoint analyses indicated the least toxic time could differ when based on other toxicity parameters (e.g., a significant least toxic time of 17:00 h was observed for G3-4 leucopenia), in agreement with animal data. The least toxic time of 10:30 h was estimated for any G3-4 gastrointestinal toxicity. This results of this study do not allow us to recommend an optimal time for vinorelbine administration. It has highlighted, however, the inherent methodological difficulties in the conduct of such a trial in the human setting. It indicates that future optimal time-finding trials should have tolerability and/or activity as the primary endpoint in place of a particular toxicity. The randomized optimal time-finding design may be used to identify the best time of chemotherapy administration.     

Clinical evaluation of the EA-rosette test in the early detection of cervical cancer

It was previously found that a negative EA-rosette test, showing EA-rosette-forming cells in a cervical cell suspension, excluded the presence of cells of invasive carcinoma (predictive value of 99.9%). This study on 2,462 patients confirmed the applicability of the EA-rosette test in screening for precancerous as well as cancerous lesions. In 98.6% of the cases of dysplasia, carcinoma in situ and invasive carcinoma, the cervical cell suspensions contained EA-rosette forming cells (the rosette test was positive). With a negative EA-rosette test, the probability of missing a specimen with class III cytology (mild/moderate dysplasia) was 1.4%, of missing one with class IV cytology (severe dysplasia/carcinoma in situ) was 0.8% and of missing one with class V cytology (invasive carcinoma) was 0.25%. The predictive value of a negative EA-rosette test was 98.6%. The false-negative rate for negative EA-rosette tests was 3.7% for invasive carcinoma, 17.5% for carcinoma in situ and severe dysplasia and 41.4% for mild to moderate dysplasia.