Meta Analise Ilib Sangue
Meta Analise Ilib Sangue
Meta Analise Ilib Sangue
1. Laboratory of Laser Sports Medicine, South China Normal University, Guangzhou, GD 510006 China
2. College of Life Science, South China Normal University, Guangzhou, GD 510631, China
3. Photon TCM Laboratory, South China Normal University, Guangzhou, GD 510631, China
ABSTRACT
Intravascular low energy laser therapy (ILELT) was put forward for cardiocirculatory diseases in USA in 1982, was
popular in Russia in 1980s, and then in China in 1990s. The therapeutic effects of ILELT and drugs in comparison with
drugs only on Chinese patients and their blood parameters were analyzed with meta-analyses and reported as (OR,
95%CI) for patient improvement and (WMD, 95% CI) for blood parameter improvement, where 95%CI, OR and WMD
denoted 95% confidence intervals, odds ratio and weighted mean difference, respectively. It was found that the patients
of cerebral infarction (2.39, 2.09~2.74) and cerebrovascular diseases (2.97, 1.69~2.53) were cured, respectively, (P <
0.01), and the symptom improvement of patients of cerebral infarction, cerebrovascular diseases and diabetes were
significant (3.13, 2.79~3.51), (4.92, 3.39~7.14) , and (3.80, 2.79~5.18), and mild (3.66, 3.15~4.24), (4.95, 2.77~8.84),
and (7.11, 4.54~11.13), respectively, (P < 0.01). It was also found that the blood parameters such as cholesterol (-0.78,
-1.32~-0.24), total cholesterol (-1.08, -1.80~-0.36), low density lipoprotein cholesterol (-0.6, -1.01~-0.19), triacylglycerol
(0.63, -0.83~-0.42), high density lipoprotein (0.34,0.10~0.59), erythrocyte aggregation index (-0.24, -0.27~-0.21),
erythrocyte Sedimentation Rate (-4.57, -7.26~-1.89), fibrinogen (-0.76, -1.31~-0.21), whole blood contrast viscosity
(-0.40, -0.69~-0.12), low cut blood viscosity (-1.2, -1.93~-0.48), high cut blood viscosity (-0.62, -0.92~-0.32), whole
blood viscosity(-1.2, -1.85~-0.54) and plasma blood contrast viscosity(-0.07, -0.12~-0.03) were found improved (P <
0.05). It is concluded that the patients of cerebral infarction, cerebrovascular diseases and diabetes might be improved
with ILELT, which might be mediated by blood parameter improvement.
1 INTRODUCTION
Photobiomodulation (PBM) is a modulation of laser irradiation or monochromatic light (LI) on biosystems, which
stimulates or inhibits biological functions but does not result in irreducible damage. The LI used in PBM is always low
intensity LI (LIL), ~10 mW/cm2. However, moderate intensity LI (MIL), 102~3 mW/cm2, is of PBM if the radiation time
is not so long that it damages organelles or cells. The PBM of LIL and MIL is called LPBM and MPBM, respectively.
*
corresponding author. Email: [email protected]
Chinese therapeutic applications of ILELT were the most widely in the world, and its basic studies such as blood
research in vitro(Mi et al 2004&2006), animal blood research in vivo (Tong et al 2000), human blood research in vivo
(Zhu 1999) and traditional Chinese medicine research (Yan et al 1999), was also very progressive in China. ILELT might
work in view of its previous research, but it should be verified by randomized placebo-controlled trial. However, there
was only one study on ILELT within the frame of evidence-based medicine. Zvereva et al. (1994) have made a
randomized placebo-controlled study of the clinical efficacy of four different methods of ILELT with He-Ne laser in 150
patients suffering from rheumatoid arthritis. The therapeutic effects of ILELT and drugs in comparison with drugs only
on patients and blood parameters were analyzed with meta-analyses in this paper.
2 META ANALYSIS
We searched reports in the Chinese National Knowledge Infrastructure (http://dlib3.edu.cnki.net/kns50/) (until May
2008) using the key words “intravascular” and “laser”. The second key word “laser” was searched on the base of result
of the first word “intravascular”. The language was Chinese.
We defined criteria for the inclusion and exclusion of literatures before analysis (Lichtenstein MJ 1987, Zodpey SP
2003). There were four rules to include the reports. First, the clinic trial included both treatment group and control group
or both the before trail data and after trail data for only one group. Second, the treatment group was treated with ILELT
and drugs. Third, both the treatment group and the control group used the same drugs which may be Chinese traditional
medicine or Western medicine. Fourth, both two groups have no significant difference in age and the degree of the
diseases before trial. There were six rules to exclude the reports. First, it was a reviewed report. Second, there were
neither numeric data nor continuous value. Third, the control group was treated with more drugs. Fourth, the control
group was also treated with ILELT. Fifth, the control group was treated with hyperbaric oxygen therapy. Sixth, it is the
repeated publication. Every report was assessed solely by two authors (Zhao SD and Wang YF). Consensus was reached
through discussion or arbitration by a third author (Liu TCY and Liu SH) before data entry. We have found high
agreement among most of them.
From each report, we recorded the published time, the journal, the first author, the report title, the drug, the disease,
the disease diagnosis standard, the age range (mean or median), the laser dose, the method of trail designed, curative
effect criteria, dichotomous data (cure number, remarkable number, effectual number, ineffectual number and the total),
and continuous value (mean and standard deviation). We then classified the data recorded into 3 kinds. The first kind of
Paired t tests were used to test the differences between treatment and control groups before trial. Every report was
first estimated for quality scale (Crowther MA et al 2007). According to allocation concealment criterion, the four levels,
adequate, unclear, inadequate, not used, were denoted as A, B, C, and D in order, respectively. We used the cochrane
collaboration software (RevMan Analyses 4.2) to analyze the data in terms of a random-effects model or fixed-effects
model, calculated the OR or WMD with 95% confidence intervals (CIs) (DerSimonian R et al 1986, Hedges LV et al
1985, Bartolucci AA 2007). Subgroup, sensitivity and bias analyses were also performed. We also tested for
heterogeneity (homogeneity) in the results of different reports using the Q statistic and considered heterogeneity to be
significant if P < 0.05(Higgins JP et al 2002). We then choose the random-effect model (if P < 0.05) and the fixed-effect
model (if P ≥ 0.05) for farther analysis. Fail-safe number (Nfs) was used to test for publication bias. The fail-safe number
means how many negative reports could change the result. And its formula: Nfs0.05= (∑Z/1.645) 2-k, k means the number
of reports we analysed. Under the P = 0. 05 conditions, according to P received from each trial get the Z from the
standard normal school table. Comparing the Nfs0.05 with 5k+1, we would think the result we received is stead-going if
Nfs0.05>5k+1, or the result we received is biased so that the reliability of the result would be lower. Funnel plot could also
help us to judge weather the result we received is biased (Egger M et al 1997, Felson D 1992). In the funnel plot, the
chosen effect and its standard error are the abscissa (adopting hyperbolic logarithm as scale) and the ordinate,
respectively, and the swatch spots are spread round an axis which is paralleling the y-axis and the whole spots is just like
an inversion funnel. The whole spots are axis symmetry if the result is steady-going. Publication bias was evaluated by
funnel plot constructing a funnel diagram originating from the pooled OR or WMD of the literatures.
3 PATIENT IMPROVEMENT
The time range of the literature we recorded is from 1995 to 2007. The analyzed diseases in the 130 dichotomous
reports were cerebral infarction, pulmonary heart disease, coronary heart disease, diabetes, angina pectoris and heart
failure and cerebrovascular disease, but hypertension, tinnitus (deafness), and neurasthenia could not be analyzed for
lacking enough data.
There were 57 reports about cerebral infarction disease. 919 patients were cured among 2964 patients in treatment
group, but 437 were cured among 2632 patients in control group. The pooled OR was 2.39 (95% CI, 2.09~2.74). There
was a significant homogeneity (P =0.99) in the result (Figure 1) and the fix-effect model was chosen. According to table
1, Nfs0.05=701, 5K+1=286, Nfs0.05>5K+1. This meant that the result was steady-going and the publication bias was lower
Table 1 has summarized the meta-analysis of the 6 diseases, pulmonary heart disease, coronary heart disease,
diabetes, angina pectoris and heart failure and cerebrovascular disease. It has also indicated that ILELT is better than
treatment only with the same drugs which was Chinese traditional medicine or Western medicine. Especially it works
43 of continuous reports recorded included 17 hemorheology variables, cholesterol, low density lipoprotein,
triglyceride, high density lipoprotein, packed cell volume of erythrocyte, erythrocyte deformation index, erythrocyte
aggregation index, hematocrit, whole blood contrast viscosity, whole blood low-shear viscosity, whole blood high-shear
viscosity, whole blood viscosity, fibrinogen, erythrocyte sedimentation rate, plasma radio viscosity, plasma viscosity, and
total cholesterol. The 17 parameters were analyzed in 6 diseases. For example, there were 6 trials on cholesterol in
analysis. There was no difference between the treatment group and control group (P = 0.25). The pooled WMD was
-0.78 (95% CI, -1.32~-0.24). This meant that ILELT with drug reduced cholesterol parameter more 0.78 mmol/L than the
drugs only using. Table 2 indicated that ILELT with drugs reduced cholesterol,low density lipoprotein, triglyceride,
whole blood contrast viscosity, whole blood high-shear viscosity, whole blood viscosity, erythrocyte sedimentation rate,
and total cholesterol. Especially it works well with decreased erythrocyte aggregation index and plasma radio viscosity
(the result more steady-going), and increased high density lipoprotein. Because of literatures’ bias, both whole blood
low-shear viscosity and fibrinogen didn’t been judged. While packed cell volume of erythrocyte, plasma viscosity and
erythrocyte deformation index didn’t reduce significantly.
5 REDOX IMPROVEMENT
The redox effects of ILELT on dogs in the only laser group have been also analyzed. In table 3, the data after trial
changed little comparing with that before trial for superoxidase dismutase (SOD) in small dose with 523 nm laser (such
as 0.5-1.5 mW, 2.0-5.0 mW). While in big dose (8.0-15.0 mW), it changed significantly. Maybe big dose resulted in cell
damnification. But in small dose with 632.8nm laser (0.5-1.5mW), ILELT enhanced the consistence of SOD. In table 4,
the data after trial changed little comparing with that before trial for malondialdehyde (MDA) in small dose (such as
0.5-1.5 mW, 2.0-5.0 mW). While in big dose (8.0-15.0 mW), it increased the consistence of MDA significantly. But in
small dose with 632.8nm laser (0.5-1.5 mW), ILELT reduced the consistence of MDA.
For lacking data about period of treatment with laser, we can’t analyse the effect of period of treatment to cure some
diseases deeply now.
As an intravascular application of MIL, ILELT should be mainly mediated by ROS (Liu et al 2008). It was
supported by the redox effects of ILELT on dogs in the only laser group as in tables 3 &4. ILELT may generate ROS.
ROS generation in whole blood can be registered with luminol-dependent chemiluminescence (LDC). Acute pneumonia
and asthmatics (Farkhutdinov et al. 2001), or bronchial asthma (Farkhutdinov et al. 2007) patients with low intensity of
blood LDC exposed to ILELT activated ROS generation and raised treatment effectiveness in low intensity of blood
LDC. After intravenous blood exposure to ILELT, patients with haemorrhagic pancreatitis exhibited inhibition of the
blood proteolytic activity, enhancement of free-radical oxidation, kallikrein-kinin system activity, blood oxygen transport,
and correction of endotoxic pancreatogenic syndrome. In addition, the positive shifts were also observed in the
immunological status, morphofunctional characteristics of the red blood cells and hemoglobin, hepatic and renal
functions (Dedenko 1989).
As Lubart et al. (2005) have pointed out, PBM induced ROS can promote antioxidation. Therefore, ILELT induced
ROS may promote antioxidation. Vitreshchak et al. (2003) have studied the effect of He-Ne laser radiation on activity of
Cu/Zn-SOD, Mn-SOD, and catalase in blood cells from patients with Parkinson's disease in vivo and in vitro. The effects
of ILELT were more pronounced than those observed in similar in vitro experiments.
MPBM in ILELT may be an homeostatic regulation (Liu et al 2008). The level of ROS was so low that there were
no effects on normal blood cells in homeostasis, but there was rehabilitation on dysfunctional blood cells far from
homeostasis. Different ROS levels activate different mitogen-activated protein kinase pathways so that ILET at different
intensity might rehabilitate ROS level, immune functions and hemorheological functions, respectively. ILET might treat
many diseases, especially infective diseases such as surgical infection, suppurative septic complications, pneumonias and
tuberculosis.
7 DISCUSSION
Antioxidant supplements, hyperbaric oxygen therapy (HBOT) and ILELT are all mediated by ROS. Their
relationships will be discussed in this section.
As a fact, ILELT and HBOT (Alleva et al. 2005, Daruwalla et al. 2006 ) share the similar mechanism from the
viewpoint of ROS generation so that their clinical applications might refer with each other. ILELT is a clinical
application of fPBM and the ROS generation of ILELT is homeostatic, but the ROS generation of HBOT might damage
cells (Alleva et al. 2005, Daruwalla et al. 2006 ) and lead to oxygen toxicity (Huang et al. 2006) and its complications
(Plafki et al. 2000). No side effects of ILELT have been found, but patients scheduled for HBO therapy need a careful
pre-examination and monitoring. If safety guidelines are strictly followed, HBO therapy is a modality with an acceptable
rate of complications (Plafki et al. 2000). However, analysis of patients with central nervous system oxygen toxicity
revealed its unpredictability and inevitability (Huang et al. 2006). Although it is common sense that patients who
develop a seizure in the hospital need help from the medical staff, it cannot be done in a monoplace hyperbaric chamber
because of pressure unequalization. Therefore, a multiplace chamber equipped with an antechamber for medical
contingency is possibly the better facility in consideration of safety (Huang et al. 2006).
Because of the documented cellular and biochemical benefits of HBOT, HBOT is applied now with increasing
frequency to various orthopedic conditions (Huang et al. 2006). Despite ongoing controversy, HBOT is frequently
administered in various clinical situations (Plafki et al. 2000). The clinical applications of ILELT and HBOT might refer
with each other since they have shared the similar mechanism from the viewpoint of ROS generation. Moreover, ILELT
might further be used in stead of HBOT because it is homeostatic.
ACKNOWLEDGMENTS: This work was supported by National Science Foundation of China (60878061,
60478048, 6017800 and 6027812), National 973 basic project of China (2005CB523502), National Postdoctoral
Foundation of China (20070420143).
-
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2000Wangdeling 15/60 9/00 2_ca 102 tO6O. Sa4t
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2004zhangzhiting 16/60 11/06 500 1.49 t062. 506t A
2005Liuy009i 26/64 14/64 299 2.44 t115. 050t A
2005Panzhifeng 10/40 0/40 1S5 2.33 t072. 709t A
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- 0.4
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0. t
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a a
a
. a
1.2
- .6
Nfs0.05=49
RC 3.80 2.79—5.18 <0.01 high
438 5K+1=36
d(7)
359
EC 7.11 4.54—11.13 <0.01 Nfs0.05>5K+1 high
In the first line of the table, PN, DG, OR, CI and RR denote patient number, disease grouping, odds ratio, confidence interval and
result’s reliability, respectively. In the first row, a, b, c, d ,e and f denote cerebral infarction, pulmonary heart disease, coronary heart
disease, diabetes, angina pectoris and heart failure, and cerebrovascular disease, respectively, with the report numbers in the bracket.
In the second row of the each line, the top and foot numbers denote the treatment group number and the control group number,
respectively. In the third row,
CC, RC and EC denote cure comparison, remarkable comparison and effectual comparison.
He (%) 21 0.02 —— —— —— —— ——
In the first line of the table, ‘before’ and ‘after’ denote before and after trial, respectively, P is the test value between treatment
group and control group, and RR denotes result’s reliability. In the first raw, Ch, LDL, Tr, HDL, PCVE, EDI, EAI, He, WBCV, WBLV,
WBHV, WBV, Fi, ESR, PRV, PV and TC denote cholesterol, low density lipoprotein, triglyceride, high density lipoprotein, packed cell
volume of erythrocyte, erythrocyte deformation index, erythrocyte aggregation index, hematocrit, whole blood contrast viscosity,
whole blood low-shear viscosity, whole blood high-shear viscosity, whole blood viscosity, fibrinogen erythrocyte sedimentation rate,
plasma radio viscosity, plasma viscosity and total cholesterol, respectively.
Table 3. Statistical calculation of dog’s superoxidase dismutase in the only laser group
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