REN Ming-Shan, ZHANG Bo, YANG Ren-Min, HAN Yong-Zhu and WANG Xun 世界华人消化杂志 1998 0 6 1
关键词： 期刊 sjhrxhzz 0 研究原著 fur -->
Subject headings Gandou decoction; dimercaptosuccinic acid; hepatolenticular
degeneration; trace elements
Abstract
AIM To investigate the curative effect of integrated traditional Chinese and western
medicine (TCM-WM) therapy in hepatolenticular dergeneration (HLD).
METHODS Eighty patients with HLD were divided randomly into two groups
(TCM-WM group and WM group), TCM-WM group (40 cases) were given
oral dimercaptosuccinic acid (DMSA) 50 mg/kg body weight, twice daily and
Gandou decoction once a day consecutively for 30 days. The efficacy was
compared with that of 40 cases treated only with DMSA as the control. The
changes of urinary trace and macro-elements were observed before and after treatment.
RESULTS The total effectiveness rate of TCM-WM group was significantly
higher than that of WM group (P<0.05), especially more patients with hepatic
type responded well to treatment with TCM-WM than with only chelating agent
DMSA. Both TCM-WM and WM therapy could obviously increase urinary
trace and macro-element excretion (P<0.01, respectively).
CONCLUSION TCM-WM therapy appears extremely promising as new
cupruretic method for treatment of HLD. It is particularly suitable for the patients
with hepatic type.
INTRODUCTIONH epatolenticular degeneration (HLD) is an autosomal
recessive disease of copper transport, resulting in copper accumulation and
toxicity to the liver and brain affecting most commonly children or young adults
and running an invariably fatal course if not adequately treated by decoppering
therapy. At present, the gene (WD) has been mapped to chromosome 13 q 14.3[1,2] ,
both increasing awareness of the etiological mechanism of the illness and the
introduction of new pharmacologic approaches to its treatment have demonstrated
that this disease is certainly preventable and to some extent is curable. This study
was designed to compare clinical therapeutic effects of TCM-WM and WM for HLD.
MATERIALS AND METHODS
Subjects
Eighty patients with HLD were chosen for this study. They were diagnosed in
accordance with the criteria proposed by Houwen[3] and were randomly
divided into integrated traditional and western medicine therapy (TCM-WM
group) and western medicine therapy (WM group). Based on clinical symptoms,
they were classified as neurological type (including Wilson type and pseudosclerosis
type) and hepatic type[4] . The severity of the disease was graded from Ⅰ to Ⅳ
according to the modified Goldstein method[5] . These two groups were comparable
for their age, sex, course of disease, clinical classification and severity (Table 1).
Table 1 Characteristics of patients of TCM-WM group and WM group | Characteristics | TCM-WM group
(n=40) | WM group
(n=40) | | Mean age (yr) | 20.48±10.90 | 19.65±7.18 | | Males/Females | 21/19 | 22/18 | | Mean course of illness (yr) | 3.5±1.5 | 3.0±1.5 | | Clinical classification | | Wilson type | 19 | 21 | | Pesudosclerosis type | 12 | 11 | | Hepatic type | 9 | 8 | | Modified Goldstein method | | Grade Ⅰ | 8 | 10 | | Grade Ⅱ | 15 | 14 | | Grade Ⅲ | 10 | 11 | | Grade Ⅳ | 7 | 5 | Therapeutic methods
All patients of TCM-WM group were given oral dimercaptosuccinic acid (DMSA).
DMSA capsules were produced by Shanghai Xinya Pharmaceutic Plant and each
pill contained 0.25 g meso-DMSA. Oral dosage was 50 mg/kg body weight, twice
daily, consecutively for 30 days, and Gandou decoction consisting of rhubarb 6 g,
Chinese goldthread 10 g, skullcap 10 g, oriental water plantain 10 g, cordate houttuynia
20 g, sun-plant 20 g and creat 20 g, was administered once a day consecutively
for 30 days. The patients of WM group were treated only with DMSA. The
administration regimen was the same as the TCM-WM group. All subjects of two
groups were advised to take a copper-poor diet throughout the course of treatment.
Before and after treatment, typing, grading and clinical curative effects were judged
and accomplished independently by two experienced neurologists in our institute,
who were not aware of the laboratory results. Meanwhile, Hitachi-208 atom
absorption spectrophotometer was used to determine urine copper, zinc, iron
and calcium content of all patients.
Therapeutic judgement criteria
Marked effectiveness. After 30 days of DMSA treatment, patient conditions
were improved remarkably by two grades.Improvement. Clinical conditions
were improved by one grade as compared with those before treatment.Inefficiency
or exacerbation. Clinical signs and symptoms had no obvious changes or became
worse.
Statistical analysis
All data were expressed as ±s. Student′s t test and Chi-square test were used
for significance ana-lysis. The difference was regarded as significant if P value was
less than 0.05.
RESULTS
Table 2 shows the therapeutic effect of two groups, from which we can see that
the total effectiveness rate (85%) of TCM-WM groups was significantly higher
than that (62.5%) of WM group (χ2 =5.23，P<0.05). There were no significant
differences in notable effectiveness rate between TCM-WM group (25%) and
WM group (15%). On the other hand, the effectiveness rate of patients with hepatic
type in WM group was obviously lower than that in TCM-WM group (χ2 =4.74，
P<0.05), which showed that therapeutic effect of TCM-WM therapy was superior
to that of only metal-binding agent DMSA. It was especially suitable for the patients
with hepatic type who had inferior response to WM therapy.
The urinary copper, zinc, iron and calcium le-vels in both groups rose remarkabley
after expectant treatment (P<0.01, respectively). In TCM-WM group, the levels
of urinary copper, iron and calcium had no differences as compared with those in
WM group. However the level of urinary zinc in TCM-WM group was significantly
higher than that in WM group (t=8.168，P<0.01), illustrating that both kinds of
therapy could effectively facilitate cupruresis (Table 3).
Table 2 Comparison of curative effect of TCM-WM and WM therapy 〔cases (%)〕 | Group | Type | n | Markedly
effective | Improved | Ineffective | Total
effectiveness | | TCM-WM | Wilson | 19 | 6(31.6) | 11(57.9) | 2(10.5) | 17(89.5) | | Pesudosclerosis | 12 | 3(25.0) | 7(58.3) | 2(16.7) | 10(83.3) | | Hepatic | 9 | 1(11.1) | 6(66.7) | 2(22.2) | 7(77.8)a | | Total | 40 | 10(5.0) | 24(60.0) | 6(15.0) | 34(85.0)a | | WM | Wilson | 21 | 4(19.0) | 12(57.1) | 5(23.8) | 16(76.2) | | Pesudosclerosis | 11 | 2(18.2) | 5(45.5) | 4(36.4) | 7(63.6) | | Hepatic | 8 | 0(0.00) | 2(25.0) | 6(75.0) | 2(25.0) | | Total | 40 | 6(15.0) | 19(47.5) | 15(37.5) | 25(62.5) | a P<0.05， compared with WM group.
Table 3 Urinary trace and macro-element changes after TCM-WM
and WM therapy (±s) | Group | Treatment
(time) | n | Copper | Zinc (μmol) | Iron | Calcium (mmol/L) | | TCM-WM | Before | 40 | 4.79±2.51 | 5.94±3.43 | 6.98±3.06 | 1.27±0.77 | | After | 40 | 17.43±7.44a | 96.47±38.69a,b | 13.55±3.53a | 4.16±2.32a | | WM | Before | 40 | 5.21±3.53 | 6.89±3.80 | 6.08±2.17 | 1.23±0.93 | | After | 40 | 16.63±9.24a | 38.24±23.16a | 12.53±3.64a | 3.47±2.12a | a P<0.01, compared with pre-treatment; b P<0.01, compared with WM group.
During the course of treatment, we observed side-effect occurrence in both TCM-WM
(7/40) and WM group (9/40). Most common adverse events in our patients were mild
fever, allergic skin rashes, small amounts of suffusion of gingiva, nasal cavity and skin,
mild abdominal distension and inappetence. There were no significant differences in
side-effect occurrence between TCM-WM group (17.5%) and WM group (22.5%)
(χ2 =0.312, P>0.05).
DISCUSSION By now, we are still not able to find a fully satisfactory therapy
for HLD, penicillamine (PCA), dimercaprol (BAL) and zinc sulfate have remained
the treatment of first choice for forty years because the drugs are readily available
and of proven efficacy in the great majority of patients. However, the use of these
drugs are associated with a wise range of toxic reactions and unsatisfactory curative
effect on the patients with hepatic type[6] . Therefore, it is necessary to further
explore new anticopper approaches for the treatment of HLD. Based on a long-term
therapeutic research on HLD, we first applied DMSA and Gandou decoction to the
treatment of HLD and opened up a broad prospects for treating HLD with TCM-WM
therapy.
According to the TCM theory, Gandou decoction is directed against the pathogenic
mechanism of copper toxin and wetness-head evil accumulated within the body.
It is composed of Chinese medicinal herbs of heat-clearing, detoxifying and wetness-
drying, rhubarb, Chinese goldthread and skullcap can eliminate hepatocystic wetness-
heat evil, oriental water plantain, cordate houttuynia, sun-plant and creat have functions
of detoxifying and promoting diuresis to eliminate the wetness-evil from the lower warmer.
Modern pharmacological research has confirmed that six cardinal remedies of Gandou
decoction are all Chinese medicinal herbs of high-zinc and low-copper content. Since
it was adopted to treat patients with HLD in 1980, Gandou decoction has achieved
satisfactory therapeutic effects on HLD[7] . However, as compared with PCA or
BAL, it has slower curative effect and less dupruresis in spite of less adverse reaction[8] .
DMSA is a broad spectrum heavy metal antidote with low toxicity and high water solubility.
It is easily discharged through urine after taken orally. We used DMSA to treat HLD in
1988 and found that DMSA could improve effectively neurologic symptoms and signs
and evidently facilitate biliary copper excretion besides clearly increasing urinary copper
exctetion. But it had inferior therapeutic effect on patients with he-patic type than patients
with neurological type[9] . Our study in treating HLD with DMSA and Gandou decoction
is to investigate the curative effect of TCM-WM therapy on HLD. The results indicated
that total effectiveness rate of TCM-WM therapy was significantly higher than that of WM
therapy (P<0.05), especially in the patients with hepatic type,TCM-WM therapy had
much better curative effect (P<0.05). Laboratory studies showed that both TCM-WM
and WM therapy could obviously increase urinary trace and macro-element excretion
of patients with HLD (P<0.01, respectively). The evidently increased urinary zinc content
by TCM-WM therapy was probably related to the fact that six cardinal herbs of Gandou
decoction are all Chinese medicinal herbs of high-zinc and low-copper content. No serious
side effects were seen through the course of treatment. There were no significant differences
in side-effect occurrence between TCM-WM group and WM group (P>0.05). In
conclusion, our findings suggest strongly that TCM-WM therapy appears extremely
promising as a new cupruretic method for treatment of HLD, it is particularly recommended
to treat the patients with hepatic type.
Institute of Neurology, Affiliated Hospital, Anhui College of T.C.M. Hefei 230031, China
REN Ming-Shan, male, born on 1958-05-30 in Hefei, Anhui Province, associate professor
of internal medicine, MS in neurology; Research Fellow of University of Rouen, France,
1994-1995; having 20 papers and one book published.
Tel. +86·551·2816764-2106
* Project supported by the National Natural Science Foundation of China, No.9570878.
Correspondence to Dr. REN Ming-Shan, Institute of Neurology, Affiliated Hospital,
Anhui College of T.C.M. Hefei 230031, China REFERENCES 1 Petrukhin K, Fischer SG, Pirastu M, Tanzi RE, Chernov I, Devoto M et al.
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Received 1997-07-10
(REN Ming-Shan, ZHANG Bo, YANG Ren-Min, HAN Yong-Zhu and WANG Xun)
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