Mu-Lien Lin

Long-term results of Taiwan Pediatric Oncology Group studies 1997 and 2002 for childhood acute lymphoblastic leukemia

The long-term outcome of 1390 children with acute lymphoblastic leukemia (ALL), treated in two successive clinical trials (Taiwan Pediatric Oncology Group (TPOG)-ALL-97 and TPOG-ALL-2002) between 1997 and 2007, is reported. The event-free survival improved significantly (P=0.0004) over this period, 69.3±1.9% in 1997–2001 to 77.4±1.7% in 2002–2007. A randomized trial in TPOG-97 testing L-asparaginase versus epidoxorubicin in combination with vincristine and prednisolone for remission induction in standard-risk (SR; low-risk) patients yielded similar outcomes. Another randomized trial, in TPOG-2002, showed that for SR patients, two reinduction courses did not improve long-term outcome over one course. Decreasing use of prophylactic cranial irradiation in the period 1997–2008 was not associated with increased rates of CNS relapse, prompting complete omission of prophylactic cranial irradiation from TPOG protocols, beginning in 2009. Decreased use of etoposide and cranial irradiation likely contributed to the low incidence of second cancers. High-risk B-lineage ALL, T-cell, CD10 negativity, t(9;22), infant, and higher leukocyte count were consistently adverse factors, whereas hyperdiploidy >50 was a consistently favorable factor. Higher leukocyte count and t(9;22) retained prognostic significance in both TPOG-97 and TPOG-2002 by multivariate analysis. Although long-term outcome in TPOG clinical trials is comparable with results being reported worldwide, the persistent strength of certain prognostic variables and the lower frequencies of favorable outcome predictors, such as ETV6-RUNX1 and hyperdiploidy >50, in Taiwanese children warrant renewed effort to cure a higher proportion of patients while preserving their quality of life.

Improved treatment results for childhood acute myeloid leukemia in Taiwan

To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C – containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51±5.3% (s.e.) and the 5-year event-free survival 50±4.8%; for APL, these were 100%, 86±7.0, and 75±9.8%. For the whole group, the 5-year survival was 57±4.7% and the 5-year event-free survival 54±4.4%. The AML-97A regimen was well tolerated.

Pain Control on Demand Based on Pulsed Radio-Frequency Stimulation of the Dorsal Root Ganglion Using a Batteryless Implantable CMOS SoC

This paper presents the implementation of a batteryless CMOS SoC with low voltage pulsed radio-frequency (PRF) stimulation. This implantable SoC uses 402 MHz command signals following the medical implanted communication system (MICS) standard and a low frequency (1 MHz) for RF power transmission. A body floating type rectifier achieves 84% voltage conversion ratio. A bi-phasic pulse train of 1.4 V and 500 kHz is delivered by a PRF driver circuit. The PRF parameters include pulse duration, pulse frequency and repetition rate, which are controllable via 402 MHz RF receiver. The minimal required 3 V RF Vin and 2.2 V VDDr is achieved at 18 mm gap. The SoC chip is fabricated in a 0.35 μm CMOS process and mounted on a PCB with a flexible spiral antenna. The packaged PRF SoC was implanted into rats for the animal study. Von Frey was applied to test the mechanical allodynia in a blinded manner. This work has successfully demonstrated that implanted CMOS SoC stimulating DRG with 1.4 V, 500 kHz PRF could significantly reduce spinal nerve ligation (SNL) induced mechanical allodynia for 3-7 days.Although pain is interpreted as the fifth vital sign by many professions, the presence of different degrees of pain significantly affects quality of life for many patients, especially the elderly [1]. Electrical stimulation to the central or peripheral neural conduction paths has been utilized in clinics to achieve effective pain relief [2]. The conventional scheme for pulsed radio-frequency (PRF) pain therapy uses thermal coagulation to permanently damage nerves by heat. This destructive method can cause severe side-effects such as hyper-sensitivity to pain after nerves regenerate. Thus, repeated surgery is needed. Additionally, the conventional design of an implantable system requires a battery for operation, often accounting for over 2/3 of the entire device volume. Therefore, a non-destructive and batteryless method using PRF for pain control is key for implantable systems. This work uses a batteryless implantable pain-control SoC that is effective in pain reduction, using a low stimulation voltage that avoids causing thermal damage to dorsal root ganglion (DRG) tissue. An animal study of neuropathic pain was previously designed with PRF parameters to control tissue temperature at ≪40°C via an external function generator [3]. This work now presents the implementation of this functionality on a CMOS SoC. Its effectiveness is demonstrated by observing the behavior of rats receiving localized bipolar stimulus to the DRG of the lumbar nerve.

Pain control on demand based on pulsed radio-frequency stimulation of the dorsal root ganglion using a batteryless implantable CMOS SoC

This paper presents the implementation of a batteryless CMOS SoC with low voltage pulsed radio-frequency (PRF) stimulation. This implantable SoC uses 402 MHz command signals following the medical implanted communication system (MICS) standard and a low frequency (1 MHz) for RF power transmission. A body floating type rectifier achieves 84% voltage conversion ratio. A bi-phasic pulse train of 1.4 V and 500 kHz is delivered by a PRF driver circuit. The PRF parameters include pulse duration, pulse frequency and repetition rate, which are controllable via 402 MHz RF receiver. The minimal required 3 V RF Vin and 2.2 V VDDr is achieved at 18 mm gap. The SoC chip is fabricated in a 0.35 μm CMOS process and mounted on a PCB with a flexible spiral antenna. The packaged PRF SoC was implanted into rats for the animal study. Von Frey was applied to test the mechanical allodynia in a blinded manner. This work has successfully demonstrated that implanted CMOS SoC stimulating DRG with 1.4 V, 500 kHz PRF could significantly reduce spinal nerve ligation (SNL) induced mechanical allodynia for 3-7 days.

Human T-lymphotropic virus type II infection in Vietnamese thalassemic patients

SummaryAnti-human T-lymphotropic virus type I/II (HTLV-I/II) antibodies were screened by particle agglutination test in a total of 66 patients with thalassemia major who received multiple transfusion from paid donors at the Blood Transfusion Hematology Center of Ho Chi Minh City in South Vietnam. HTLV-II infection was confirmed in 6 patients (9.1%) by Western blot analysis and/or polymerase chain reaction. Phylogenetic analysis revealed that long terminal repeat sequences of HTLV-II proviruses from 5 thalassemic patients in Vietnam belonged to the same phylogenetic subgroup of HTLV-IIb as those from intravenous drug abusers in North America and Europe. These data shed light on the route of introducing HTLV-II into Vietnam.

A Dual-Mode Highly Efficient Class-E Stimulator Controlled by a Low-Q Class-E Power Amplifier Through Duty Cycle

This paper presents the design flow of two high-efficiency class-E amplifiers for the implantable electrical stimulation system. The implantable stimulator is a high-Q class-E driver that delivers a sine-wave pulsed radiofrequency (PRF) stimulation, which was verified to have a superior efficacy in pain relief to a square wave. The proposed duty-cycle-controlled class-E PRF driver designed with a high-Q factor has two operational modes that are able to achieve 100% DC-AC conversion, and involves only one switched series inductor and an unchanged parallel capacitor. The measured output amplitude under low-voltage (LV) mode using a 22% duty cycle was 0.98 V with 91% efficiency, and under high-voltage (HV) mode using a 47% duty cycle was 2.95 V with 92% efficiency. These modes were inductively controlled by a duty-cycle detector, which can detect the duty-cycle modulated signal generated from the external complementary low-Q class-E power amplifier (PA). The design methodology of the low-Q inductive interface for a non-50% duty cycle is presented. The experimental results exhibits that the 1.5-V PA that consumes DC power of 14.21 mW was able to deliver a 2.9-V sine wave to a 500 Ω load. The optimal 60% drain efficiency of the system from the PA to the load was obtained at a 10-mm coupling distance.

The development and evaluation of the citizen telehealth care service system: Case study in taipei

Because of the rapid aging population in Taiwan and the trend of fewer children, people are looking into technical solutions for continuous/intermittent monitoring of vital signs in the home setting environment and the interactions between family members. In this study we developed a smart medical services system for managing chronic disease, called Citizen Telemedical Care service System (CTCS). The system integrates biosignal measurement, hypertension risk estimation expert system, clinic appointment service, video communication service, medical assistance referral, health frequency program record, and health/hygiene education. The demo version CTCS is exhibited in the center of INSIGHT opened for visit and trial use. In order to verify the demand and acceptability of the system and services, we have interviewed 251 volunteers with a questionnaire survey with the help from Taipei City Government. The results showed that people have positive expectation about the service program for health care and the capability of home devices. They also expressed high motivation on learning to use the system and to participate in the program. According to the evaluation results, the system is processing a small user test led by Taipei City Government, in order to further verify the acceptability and satisfaction of the system.

In Situ Measurement of Tissue Impedance Using an Inductive Coupling Interface Circuit

In this work, a method of an inductive coupling impedance measurement (ICIM) is proposed for measuring the nerve impedance of a dorsal root ganglion (DRG) under PRF stimulation. ICIM provides a contactless interface for measuring the reflected impedance by an impedance analyzer with a low excitation voltage of 7 mV. The paper develops a calibration procedure involving a 50-Ω reference resistor to calibrate the reflected resistance for measuring resistance of the nerve in the test. A de-embedding technique to build the equivalent transformer circuit model for the ICIM circuit is also presented. A batteryless PRF stimulator with ICIM circuit demonstrated good accuracy for the acute measurement of DRG impedance both in situ and in vivo. Besides, an in vivo animal experiment was conducted to show that the effectiveness of pulsed radiofrequency (PRF) stimulation in relieving pain gradually declined as the impedance of the stimulated nerve increased. The experiment also revealed that the excitation voltage for measuring impedance below 25 mV can prevent the excitation of a nonlinear response of DRG.

A comparison between pulsed radiofrequency and electro-acupuncture for relieving pain in patients with chronic low back pain.

Many treatment options for chronic low back pain are available, including varied forms of electric stimulation. But little is known about the electricity effect between electro-acupuncture and pulsed radiofrequency. The objective of this study is to assess the difference in effectiveness of pain relief between pulsed radiofrequency and electro-acupuncture. Visual analog score (VAS) pain score, the Oswestry disability index (ODI) to measure a patients permanent functional disability, and Short form 36 (SF-36) which is a survey used in health assessment to determine the cost-effectiveness of a health treatment, were used as rating systems to measure the pain relief and functional improvement effect of pulsed radiofrequency and electro-acupuncture, based on the methodological quality of the randomized controlled trials, the relevance between the study groups, and the consistency of the outcome evaluation. First, the baseline status before therapy shows no age and gender influence in the SF-36 and VAS score but it is significant in the ODI questionnaire. From ANOVA analyses, it is apparent that radiofrequency therapy is a significant improvement over electro-acupuncture therapy after one month. But electro-acupuncture also showed functional improvement in the lumbar spine from the ODI. This study provides sufficient evidence of the superiority of pulsed radiofrequency (PRF) therapy for low back pain relief compared with both electro-acupuncture (EA) therapy and the control group. But the functional improvement of the lumbar spine was proved under EA therapy only. Both therapies are related to electricity effects.

Subtyping of human T-lymphotropic virus type I by amplification of long terminal repeat sequences and restriction fragment length polymorphism analysis in carriers with multiple transfusions

Abstract Five major subtypes of human T-lymphotropic virus type I (HTLV-I) have been proposed: cosmopolitan, Japanese, West African, Central African, and Melanesian. Based on nucleotide variations specific to particular subtypes, it was possible to genotype HTLV-I rapidly by restriction fragment length polymorphism (RFLP) studies following polymerase chain reaction (PCR) . In this study, the restriction patterns of two LTR fragments were analyzed using eight restriction endonucleases (AvaI, Eco57I, BsoFI, NdeI, SacI, DraI, MaeII, and MaeIII). Genotyping of HTLV-I was done in nine patients with adult T-cell leukemia or HTLV-I-associated myelopathy/tropical spastic paraparesis, in three prostitutes, and in 19 carriers with multiple transfusion in Taiwan. The subtyping results of RFLP studies using these eight restriction endonucleases were in accordance with those of phylogenetic analysis. A substitution of G by A at nucleotide position 503, which creates the DraI site but suppresses the SacI site, was found not only in the Japanese subtype but also in a minority of the cosmopolitan subtype. A mutation near the position of subtype-specific nucleotide variations might suppress the restriction site and lead to unexpected restriction patterns. Amplification of more than one proviral fragment and RFLP studies with a group of appropriate restriction endonucleases may provide rapid and accurate genotyping of HTLV-I. More carriers are required to evaluate the possibility of mixed infection with different HTLV-I subtypes.