Changes in muscle temperature induced by 434 MHz microwave hyperthermia

Objective

To investigate the changes in temperature of human muscle during microwave hyperthermia.

Methods

Skin surface and muscle temperatures were measured in 11 healthy adult men (mean (SD) age 24.3 (2.2) years; height 174.2 (6.1) cm; weight 70.0 (5.3) kg) during a 30 min exposure of the thigh to 434 MHz microwave hyperthermia. Skin temperature was maintained at the pilot temperature of 40°C, and the temperature of the water in the bolus was 38°C. The peak power output was set at 60 W and controlled automatically to maintain the pilot temperature. The temperature was measured in the vastus lateralis muscle at an average muscle depth of 2.0 (0.2) cm, using a 23 G Teflon‐shielded thermocouple. Biopsy specimens were obtained for light microscopy from three subjects. A muscle‐equivalent phantom was used to evaluate the vertical heating pattern.

Results

Both skin and muscle temperatures increased from baseline, and muscle temperature was higher than skin temperature (skin temperature 39.2 (0.5)°C, temperature rise 5.0 (1.5)°C; muscle temperature 43.7 (0.8)°C, temperature rise 8.9 (1.4)°C). At the end of the hyperthermia treatment, muscle temperature decreased to 39.8 (0.9)°C, but was still 4.8 (1.5)°C higher than the baseline. No signs of muscle damage were observed on the basis of the blood creatine kinase activity and histological sections.

Conclusions

The results show that the 434 MHz microwave hyperthermia treatment increased and maintained muscle temperature locally by 6.3–11.4°C without muscle damage. These findings suggest that the microwave hyperthermia system provides effective and safe treatment.For many years, heat treatment has been used as a therapy for muscle tissue injured in sports. There are several heating modalities, including silicon gel hot packs, whirlpools, paraffin baths, ultrasound and electromagnetic waves.¹ Most of these modalities are classified as superficial heating, and primarily cause a temperature increase in structures up to 1 cm below the skin surface. Ultrasound and electromagnetic waves (eg, radiofrequency and microwaves) are used for deep heating at tissue depths of 3–5 cm.²To gain therapeutic benefit, the target tissue depth and temperature should be considered when choosing the appropriate thermal modality. When deep skeletal muscle (over a small region) is targeted for heat treatment, both ultrasound and microwaves are used clinically because both modalities are thought to effectively heat the target tissue. Garrett et al³ evaluated the changes in gastrocnemius muscle temperature induced by short‐wave diathermy, and found that 20 min of microwave exposure induced an increase of 4.6°C in muscle temperature. Another study reported that ultrasound produced a mean temperature rise of 3.5°C in the gastrocnemius–soleus complex.⁴ A few comparative studies have examined the use of heat modalities on living tissue, such as muscle, and reported that electromagnetic waves are more effective than ultrasound.^3,5 In general, the therapeutic range for sports medicine is assumed to be from 41°C to 45°C.⁶ However, the increase in temperature may depend on the thermal modality.Recently, 434 MHz hyperthermia has been introduced in physical medicine and rehabilitation. Hyperthermia treatment with this equipment was reported to be a highly innovative and reliable modality for treating acute muscle injuries in sports.^5,7,8 These reports mentioned that 434 MHz hyperthermia treatment significantly reduces the pressure pain and pain on active contraction, but they did not determine muscle temperature during treatment. To our knowledge, only one report⁹ has measured the changes in temperature, and it used a phantom. The therapeutic benefits of hyperthermia treatment are related to the target‐tissue temperature and changes in temperature; so the change in temperature with treatment should be measured to assess the therapeutic benefits. Measuring the temperature can also provide evidence for the safety of the treatment. Nevertheless, the changes in human muscle temperature have not been reported because it is difficult to measure muscle temperature in a clinical setting. Therefore, we investigated the changes in the temperature of human muscle induced by a 434 MHz microwave hyperthermia system to provide evidence for its clinical effectiveness and safety.     

Radioresistant cells expressing TLR5 control the respiratory epithelium's innate immune responses to flagellin

Bacterial products (such as endotoxins and flagellin) trigger innate immune responses through TLRs. Flagellin‐induced signalling involves TLR5 and MyD88 and, according to some reports, TLR4. Whereas epithelial and dendritic cells are stimulated by flagellin in vitro, the cell contribution to the in vivo response is still unclear. Here, we studied the respective roles of radioresistant and radiosensitive cells in flagellin‐induced airway inflammation in mice. We found that i.n. delivery of flagellin elicits a transient change in respiratory function and an acute, pro‐inflammatory response in the lungs, characterized by TLR5‐ and MyD88‐dependent chemokine secretion and neutrophil recruitment. In contrast, TLR4, CD14 and TRIF were not essential for flagellin‐mediated responses, indicating that TLR4 does not cooperate with TLR5 in the lungs. Respiratory function, chemokine secretion and airway infiltration by neutrophils were dependent on radioresistant, TLR5‐expressing cells. Furthermore, lung haematopoietic cells also responded to flagellin by activating TNF‐α production. We suggest that the radioresistant lung epithelial cells are essential for initiating early, TLR5‐dependent signalling in response to flagellin and thus triggering the lung's innate immune responses.     

Induction of adaptive immunity by flagellin does not require robust activation of innate immunity

The ability of TLR agonists to promote adaptive immune responses is attributed to their ability to robustly activate innate immunity. However, it has been observed that, for adjuvants in actual use in research and vaccination, TLR signaling is dispensable for generating humoral immunity. Here, we examined the role of TLR5 and MyD88 in promoting innate and humoral immunity to flagellin using a prime/boost immunization regimen. We observed that eliminating TLR5 greatly reduced flagellin‐induced cytokine production, except for IL‐18, and ablated DC maturation but did not significantly impact flagellin's ability to promote humoral immunity. Elimination of MyD88, which will ablate signaling through TLR and IL‐1β/IL‐18 generated by Nod‐like receptors, reduced, but did not eliminate flagellin's promotion of humoral immunity. In contrast, loss of the innate immune receptor for profilin‐like protein (PLP), TLR11, greatly reduced the ability of PLP to elicit humoral immunity. Together, these results indicate that, firstly, the degree of innate immune activation induced by TLR agonists may be in great excess of that needed to promote humoral immunity and, secondly, there is considerable redundancy in mechanisms that promote the humoral immune response upon innate immune recognition of flagellin. Thus, it should be possible to design innate immune activators that are highly effective vaccine adjuvants yet avoid the adverse events associated with systemic TLR activation.     

Expression levels of drug-metabolizing enzyme, transporter, and nuclear receptor mRNAs in a novel three-dimensional culture system for human hepatocytes using micro-space plates

We evaluated a novel three-dimensional primary culture system using micro-space plates to determine the expression levels of 61 target (drug-metabolizing enzymes, transporters, and nuclear receptors) mRNAs in human hepatocytes. We measured mRNA expression levels of many target genes in four lots of cryopreserved human hepatocyte primary cells after 120 h of culture and compared differences in mRNA expression levels between cultures using traditional plates and those using micro-space plates. In this study, we show that the mRNA levels of many experimental targets in human hepatocytes before inoculation resemble the levels inside the human liver. Furthermore, we show that the rate of change of expression levels of many target mRNAs relative to the value before inoculation of the hepatocytes into micro-space plates was relatively smaller than the rate of change in hepatocytes inoculated into traditional plates. Pharmacokinetics-related examinations using this system are possible within a time frame of 120 h. We report that this novel three-dimensional culture system reproduces mRNA expression levels that are nearer to those in the liver in vivo and is an excellent platform for maintaining mRNA expression levels of drug-metabolizing enzymes and transporters when compared to common monolayer cultures.     

Advanced maxillary sinus cancer treated with concurrent chemoradiotherapy with intra-arterial cisplatin/docetaxel and oral s-1: own experience and literature review

Intra-arterial (IA) chemotherapy for head and neck cancer is effective and multiple IA concurrent chemoradiation (CCRT) protocols have been reported. However, the role of IA CCRT in the multimodality treatment of head and neck cancer is still controversial. We have treated 5 cases of unresectable T4 maxillary sinus squamous cell carcinoma with IA cisplatin (CDDP) and docetaxel (DOC) and CCRT with oral S-1. We report our experience and the effectiveness and feasibility of this combination as an alternative choice of treatment for inoperable head and neck cancer. The patients received an IA infusion of CDDP (50-70 mg/m(2)) and DOC (50-60 mg/m(2)) through the femoral artery, followed by CCRT with oral S-1. The IA infusion was repeated up to 3 times and the radiation was dosed at up to 60-70 Gy. Complete response was achieved in 4 patients and partial response in one, giving an overall response rate of 100%. The most common grade 3 or 4 toxicities were anorexia (80%), mucositis (80%) and leukopenia (80%), all of which were manageable. CCRT with IA CDDP/DOC and oral S-1 was effective and tolerated. Although preliminary, the response rate encourages further pursuit and definitive evaluation of this combination for the treatment of inoperable advanced head and neck cancer.     

TAK1 is required for the survival of hematopoietic cells and hepatocytes in mice

Transforming growth factor beta-activated kinase 1 (TAK1), a member of the MAPKKK family, is a key mediator of proinflammatory and stress signals. Activation of TAK1 by proinflammatory cytokines and T and B cell receptors induces the nuclear localization of nuclear factor kappaB (NF-kappaB) and the activation of c-Jun N-terminal kinase (JNK)/AP1 and P38, which play important roles in mediating inflammation, immune responses, T and B cell activation, and epithelial cell survival. Here, we report that TAK1 is critical for the survival of both hematopoietic cells and hepatocytes. Deletion of TAK1 results in bone marrow (BM) and liver failure in mice due to the massive apoptotic death of hematopoietic cells and hepatocytes. Hematopoietic stem cells and progenitors were among those hematopoietic cells affected by TAK1 deletion-induced cell death. This apoptotic cell death is autonomous, as demonstrated by reciprocal BM transplantation. Deletion of TAK1 resulted in the inactivation of both JNK and NF-kappaB signaling, as well as the down-regulation of expression of prosurvival genes.     

Adult T-cell leukemia/lymphoma with multiple integration of HTLV-1 provirus presenting as an isolated paranasal sinus tumor: a case report

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive T-cell lymphoma and etiologically associated with human T-lymphotropic virus type 1 (HTLV-1). Patients with ATLL commonly present with leukemic changes, systemic lymphadenopathy, and/or extranodal lesion and have very poor prognosis. METHODS AND RESULTS: We describe a rare case of ATLL presenting as an isolated paranasal mass. Southern blot analysis of the biopsied specimens demonstrated multiple integration bands of HTLV-1 provirus of different intensities. Chemotherapy resulted in complete resolution of the paranasal mass. Thereafter, the patient showed an indolent clinical course with leukemic changes and pulmonary and cutaneous ATLL lesions and remains alive more than 5 years from diagnosis. CONCLUSION: ATLL should be included in the differential diagnosis of sinonasal lymphoma, although the event is rare. Multiple HTLV-1 provirus integrations of different intensities may be indicative of good prognosis for ATLL.     

Randomized controlled trial of two forms of self-management group education in Japanese people with impaired glucose tolerance

The aim of this study was to determine the effectiveness of education on diabetes prevention in subjects with impaired glucose tolerance. A total of 100 subjects of impaired glucose tolerance with hemoglobin A1c (HbA1c) levels >/=5.5 to <6.1% were assigned randomly to either support or control groups. All subjects received education in 8 sessions over a 6-month period. The support group consisted of 10 members collaborating with a dietitian or a nurse who learned coping skills by employing a participant-centered approach. Participants in the support group were required to keep a diary that monitored weight, food intake and blood glucose levels, while the control group attended several lectures. Subjects assigned to the support group had a reduction in mean HbA1c levels from 5.77 +/- 0.36% at baseline to 5.39 +/- 0.24% at the endpoint (p<0.01). Weight, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels also decreased (p<0.01) in the support group, whereas subjects in the control group had no observable reduction in these indices. After intervention, participants of the support group had improvements in their 2-h post-meal blood glucose levels. Support group education can be effective for improving glycemic control in participants when carried out in collaboration with educators and other team members.     

Life-style and environmental factors in the development of nasal NK/T-cell lymphoma: a case-control study in East Asia

Cases of nasal NK/T-cell lymphoma (NKTCL) occur occasionally in Asian and Latin American countries but rarely in Western countries. The etiological role of life-style and environmental factors in nasal NKTCL was investigated. Five university hospitals in Japan and one each in Korea and China participated in this study; a total of 88 cases and 305 hospital controls were accrued during 2000-2005. The odds ratio (OR) of NKTCL obtained after adjustments of age, sex and country was 4.15 (95% confidence interval (CI), 1.74-9.87) for farmers, 2.81 (CI, 1.49-5.29) for producers of crops, 4.01 (CI, 1.99-8.09) for pesticide users, 11.65 (CI, 1.17-115.82) for residents near garbage burning plants, 2.95 (CI, 1.25-6.95) for former drinkers, and 0.49 (CI, 0.23-1.04) for current smokers. The ORs for crop producers, who minimized their exposure to pesticides by using gloves and glasses, and sprinkling downwind at the time of pesticide use, were 3.30 (95% CI, 1.28-8.54), 1.18 (95% CI, 0.11-12.13) and 2.20 (95% CI, 0.88-5.53), respectively, which were lower than those for producers who did not take these precautions. Exposure to pesticides and chemical solvents could be causative of NKTCL. Taken together, life-style and environmental factors might be risk factors for NKTCL.