SUMMARY

This report represents the materials of clinical applications of the Electronic Normalizer (EN) produced by ECOMED Research & Production Association to treatment of constipation of various etiology.

With comparative analysis of the results of treatment of various groups of patients, a significantly higher effect produced by the Autonomous Electrostimulator on the motor function of gastrointestinal tract was observed as compared to the therapy accepted in the world practice. Use of functional methods to control the status of large intestine enabled to confirm the positive effect on pathogenesis from application of the Electronic Normalizer for treatment of chronic constipation.
 

INTRODUCTION

Electrostimulation is a method to affect the organism with electric current in order to activate the function of any organ. Electrostimulation is based on the progress of replacement of the defected nervous impulse, which is generated by the organism, with the electric impulse generated by the apparatus that results in regeneration of all the mechanism controlling the nervous and muscular systems. With respect to the technical characteristics of the stimulating current (frequency and shape of impulse, mode, etc.), as well as with respect to the method of application, electrostimulation provides normalization of the lost functions of the organism, primarily, the contractile ability of muscular structures; as a result, the gastrointestinal tract increases its peristaltic activity together with increase in the energetic potential of intestinal muscles, activity of enzymatic systems, improvement of blood circulation in the organ stimulated and organism in the whole. Schematically, the effect of stimulating current on the organism can be represented as follows: electrical stimulation -> receptors -> nervous routes (ascending route) -> control center (central nervous system) -> nervous routes (descending routes) -> executive organ (muscular structures).

For many years, the State Research Center of Coloproctology (Russian Federal Ministry of Public Health and Medical Industry) has been designing and introducing into clinical practice various methods for electrostimulation of organs in the gastrointestinal tract as well as the equipment to provide such stimulation. Under monitoring with objective methods estimating the functional status of organs in the gastrointestinal tract, first in experiments with animals and then in clinics, the parameters of stimulating currents are developed. Various versions of cutaneous and internal electrostimulation are applied together with stimulation through electrodes in vivo. The results of this great study were reported in the First and Second Conferences on Electrical Stimulation of Organs and Tissues held in Kaunas (1975) and Kiev (1979) respectively, as well as published in periodical press.

The technical solution, which enabled to create the autonomous stimulators in the form of capsules suitable for peroral, opened the period of stimulators of new generation and, therefore, significantly extended the capacities of electrostimulation of organs of the gastrointestinal tract, because it provided the opportunity to affect directly the mucous membranes of the gastrointestinal tract with non-wounding low-energy signals.

The goal of this study was to estimate the efficiency in application of the Electronic Normalizer - Autonomous Electrostimulator of Gastrointestinal Tract and Mucous Membranes (hereinafter referred to as the "Electronic Normalizer" or "EN") produced by ECOMED Research & Production Association to treatment of one group from a wide range of complicated pathologies of the gastrointestinal tract, namely, chronic constipation, as compared to the standard drug scheme applied to treatment of chronic constipation in the State Research Center of Coloproctology and in the world practice. With its technical parameters, the Electronic Normalizer complies with the specification of TU 9444-014-11555014-97.

On order to determine the efficiency in application of the Electronic Normalizer to treatment of chronic constripation, we thought expedient to use, in addition to the clinical estimation of the patient status (subjective feelings, stool frequency, effect duration, etc.), objective methods to study the functional status of large intestine before and after treatment for all the patients.

METHODS

Protocol of study
The principal functions of large intestine include formation and further motion of the intestinal contents; however, realizing these functions, large intestine may be subjected to various disorders, which result in the phenomena of constipation. With respect to the preferential localization of these principal disorders in functioning of large intestine, chronic constipation are classified into cologenic (principal disorders in the functional status are localized in the large intestine) and rectoanal (disorders in the motor and evacuator function of rectum and anal sphincter as well as of the muscles in pelvic bottom). The differential diagnosis of the kind of chronic constipation is carried out on the basis of the clinical data as well as with the results of instrumental and functional methods of studies, which are applied to all the patients with this pathology in our institution.

Cologenic constipation is the most common pathology in the group of chronic constipation; therefore, in order to make statistically reliable generalization, the principal and control groups were formed from patients with cologenic constipation.

In order to provide the reliable data with the results of application of the Electronic Noprmalizer to treatment of chronic constipation, we carried out thorough selection of patients to make uniform groups, and the principal and control groups included only the patients with cologenic constipation, which decease reduced both the contractile ability and nervous and reflex activities of the nervous and muscular systems of large intestine. The test excluded the patients, who had earlier operations in the organs of alimentary system, as well as the patients, who suffered from additional chronic diseases of other systems.

In addition, in order to determine the possible applications of the Electronic Normalizer to treatment of rectoanal constipation, the test included the additional group of patients, who suffered from rectoanal constipation and whose age and sex distributions were similar to those in the principal and control groups of patients.

The Electronic Normalizer was used as the only treatment of 66 patients with cologenic constipation in the age of 17 to 73 years (average age 45.5 ± 6.8 years). There were 47 women and 19 men, i. e. the number of women in the principal group was by 2.5 times greater than the number of men.

Table 1. Sex and age distributions of patients in the principal group (cologenic constipation).

Sex	< 20	20-29	30-39	40-49	50-59	60-69	> 70	Total
Men	-	2	5	3	2	4	3	19
Women	3	9	9	10	10	4	1	47
Total	3	11	14	13	12	84	1	66

In analysis of the kind of occupation (profession) of the patients suffering from constipation in the principal group, we noted that most of them were persons of intellectual labor (42 patients or 63.7 per cent), including economists, teachers, engineers, programmers, medical workers, and students. From the remaining 24 patients, 15 persons (22.7 per cent) were retired, and 9 persons (13.6 per cent) were employed in various kinds of active work (drivers, workers, technicians, and agricultural workers).

The principal complaint of all the patients was disorder in the regular evacuation of intestines. Evacuation of intestines is considered as normal if a person has stool from once in two days to two times a day, and the act of defecation should not be accompanied with excess forces. Evacuation of intestines less frequently than two times a week is considered as constipation. Among the patients in the principal group, only 27 persons (40.9 per cent) had self-maintained stool with the frequency of once in three days to once a week (see Table 2). The remaining patients, who suffered from constipation, had earlier used widely various purgatives and by the moment of application of the Electronic Normalizer could initiate stool only with cleansing enemas (together with increased amount of purgatives used).

Table 2. Self-maintained stool frequency of patients with chronic cologenic constipation.

Stool frequency	Men	Women	Total
Once in three days	9	6	15  (55.5%)
Once in four or five days	4	3	7  (25.9%)
Once a week	3	2	5  (18.6%)
Total	16	11	27(100.0%)

The duration of disease of the patients in the principal group was one to five and more years (see Table 3), while 50 per cent of the patients suffered from constipation for two to four years.

Table 3. Distribution of patients with respect to disease duration.

Disease duration	Men	Women	Total
1 - 2 years	2	13	15  (22.7%)
2 - 4 years	10	23	33  (50.0%)
5 and more years	7	11	18  (27.3%)
Total	19	47	66(100.0%)

The reference (control) group included 36 patients with cologenic constipation, and the criteria for selection of patients in this group were similar to those in the principal group of patients. All the patients passed full clinical, instrumental, and functional examination. The patients of the control groups were given the course of drug therapy accepted in the State Research Center of Coloproctology, including the preparations, which regulate the motor function of gastrointestinal tract in the large intestine: Debridat (France), 200 mg three times daily, and Motillium (France), 10 mg three times daily; in addition, Methiospasmil Germany, 1 tablet three times daily, was used for tone normalization of intestinal wall for the patients with spasmic phenomena. In order to increase the volume of intestinal contents, all the patients in the control group were given the preparations, which swell in the opening of large intestine and absorb water. These preparations, which are not decomposed by the enzymes of gastrointestinal tract, promote formation of the intestinal contents. We used Mukofalk (Germany) or Agiolax (Germany), one teaspoonful with water two times daily. The appropriate drinking regime and diet was prescribed. After the course of treatment for 30 days, all the patients were subjected to control examinations.

Table 4. Sex and age distributions of patients in the control group.

Sex	< 20	20-29	30-39	40-49	50-59	60-69	Total
Men	-	1	4	3	2	2	12
Woman	1	2	6	8	4	3	24
Total	1	3	10	11	6	5	36

Like the principal group, the control group included significanlty more women than men, who suffered with chronic cologenic constipation. All the patients had complaints for constipation, while 15 patients had irregular self-maintained stool, which frequency is represented in Table 5, and the remaining 21 patients could achieve evacuation of intestines only with cleansing enemas.

Table 5. Self-maintained stool frequency of patients in the control group.

Stool frequency	Men	Women	Total
Once in three days	1	5	6  (40.0%)
Once in four or five days	3	3	6  (40.0%)
Once a week	1	2	3  (20.0%)
Total	5	10	15(100.0%)

Table 6. Distribution of patients in the control group with respect to disease duration.

Disease duration	Men	Women	Total
1 - 2 years	2	4	6  (16.6%)
2 - 4 years	7	15	22  (61.1%)
5 and more years	3	5	8  (22.3%)
Total	12	24	36(100.0%)

Therefore, the principal and control groups of patients were similar with respect to the nature and duration of their diseases, had similar symptoms of diseases and age and sex parameters.

The additional group of patients suffering from rectoanal chronic constipation included 16 persons (12 women and 4 men). The average age of these patients with rectoanal constipation was similar to that in the principal group of patients ( 44,1 ± 4,7 years).

The pathogenesis of rectoanal chronic constipation includes the following essential factors: disordered contractile ability of rectum, disordered sensitivity of rectum with respect to filling and urges, spasm of internal sphincter, disordered reaction of puborectal loop to exertion, etc. In this connection, the principal complaint of patients, who suffer from rectoanal constipation, include disorder in full evacuation of intestines, problematic and prolonged defecation, as well as painful feelings in the course of defecation. Due to many factors resulting in rectoanal constipation, treatment of patients with this form of constipation makes a complicated problem in the practice of physicians in the whole world. In recent years, positive results were obtained by application of biofeedback method for treatment of patients with rectoanal constipation (Villani J.D. at al. Biofeedback and electrostimulation as rehabilitative therapy of rectoanal constipation. Coloproctology 1994.16, No. 2,115). Our experience in application of this method to treatment of chronic constipation demonstrated its efficiency for 50 per cent of patients.

Among 16 patients with rectoanal constipation, 10 patients had complaints for disordered process of defecation, and the remaining patients had complaints for the lack of desire to evacuate intestines even after long absence of defecation.

After comprehensive clinical and functional examinations, the patients with rectoanal constipation showed the following disorders: disordered rectal sensitivity (7 patients), spasm of internal sphincter (5 patients), and spastic status of pelvic bottom muscles, including paradoxical reaction of puborectal loop (4 patients). Our study of the motor activity of rectum revealed a decrease in its contractile ability, which likely had a secondary nature.

Procedures for application of the Electronic Normalizer.
The Electronic Normalizer was applied by the patients with cologenic diseases in the morning before meals without preliminary procedures by swallowing in the presence of physicians. For this purpose, the Electronic Normalizer was unpacked, tested for good condition with the indicator, placed on the root of tongue, and swallowed with water (two or three mouthfuls). No problems were noted, when the stimulator was swallowed, most patients felt slight "pinching" of tongue at the moment of swallowing that was accounted for by the instrument switching on at contact with the electrolytic medium in the oral cavity.

For the patients suffering from rectoanal constipation, the procedure for application of the Electronic Normalizer was different from that used for treatment of patients in the principal group. For rectoanal disorders, we used two Electronic Normalizer for the course of therapy. The first Electronic Normalizer was used rectally to correct the disorders in the distal section of rectum. These patients used the Electronic Normalizer daily as suppository and inserted it for two or three hours and then removed it by exertion. The Electronic Normalizer was washed with water and soap, dried, and placed in a dry place for the next day. In ten days, the patients used the second Electronic Normalizer, in accordance with the procedure described above for the patients with cologenic constipation.

Estimation criteria.
The efficiency of therapy using the Electronic Normalizer was estimated with both the subjective criteria (stool frequency and feeling of full evacuation of intestines) and the results of clinical and functional investigations. In order to provide objectivity of the results obtained, we used the following research procedures.

Enterocolography - method for estimation of the functional status of small and large intestines by recording their electrical activy. These records were made with Enterograph and Colograph instruments equipped with cutaneous electrodes placed in the projection of the organs studied. For comparative estimation of the results of therapeutical effect of the Electronic Normalizer, we selected the index of the integral electrical activity of large intestine.


Electromanometering - method for estimation of the motor activity of large intestine by recording the endocavitary pressure with the five-channel probe inserted in the opening of large intestine. We studied the background and stimulated (by food and mechanical irritation) motor function. We estimated the following parameters: motor activity index, intestinal wall tone, endocavitary pressure, amplitude and time characteristics, and motor activity wave spectrum.


Sensometering - method for estimation îf the sensitivity of rectum to filling by dosed step-wise irritation of rectum with a cylinder inserted in its opening and recording the subjective feeling of the patient.

Table 7. Duration of the Electronic Normalizer staying for patients with chronic cologenic constipation.

Duration of EN stay in organism	Number of patients
	Absolute	Percentage
< 24 hours	-	-
24 - 48 hours	4	6.1
48 - 72 hours	20	30.3
72 - 96 hours	28	42.4
96 - 120 hours	8	12.2
> 120	6	9.0
Total	66	100.0

The duration of the Electronic Normalizer staying in the gastrointestinal tract was determined by the initial status of the gastrointestinal tract. For the patients, who suffered from chronic constipation but had irregular self-maintained stool, the time of passing did not exceed 72 hours, while for the patients, who had absolutely no self-maintained evacuation of intestines, this time increases and exceeded 72 hours in most cases.

For estimation of the efficiency of the Electronic Normalizer, we classified the results as satisfactory, and unsatisfactory. We considered the results of treatment as good if the stool frequency bacame stable and normal (once or twice in two days) and the symptoms of discomfort during and after defecation disappeared. We considered the results of treatment as satisfactory if self-maintained stool appeared for the patients, who had not it earlier, however, this stool was irregular. We estimated the results as unsatisfactory if no improvement was observed.

Good results of treatment were noted for 54 of 66 patients in the principal group (81.8 per cent), satisfactory results were achieved for 5 patients (7.5 per cent), and only 7 patients (10.7 per cent) showed no effect.

We carried out the comparative analysis of the results in treatment of cologenic constipation in dependence of the presence of self-maintained stool before starting the treatment. For 17 patients who had at least irregular but self-maintained stool before starting the treatment, we observed the positive effect in all the cases; therefore, this category of patients achieved the most favorable results after application of the Electronic Normalizer; it is interesting to note that the most patients in this group were men (13 persons of 17).

For the patients, who suffered from rectoanal constipation, as a criterion of improvement, in addition, to normalization of the stool frequency, we noted facilitation of the defecation process. From 16 patients, who suffered from rectoanal constipation, good and satisfactory results of treatment with two Electronic Normalizers were considered for 12 patients (75 per cent). The obtained data in application of the Electronic Normalizer to treatment of rectoanal constipation exceed in efficiency the results of treatment of this pathology by other methods. In the individual analysis of the results of treatment with respect to the initial functional status of rectum and locking system, we noted that the effect from application of the Electronic Normalizer was absent for 4 patients, who suffered from spasm of bottom pelvic muscles, that indicates the necessity of searching for different methods to treat these disorders, because at the present time there are no radical methods in the world to treat this pathology.

Our functional investigations (electrocolography and electromanometering) before and after application of the Electronic Normalizer to gastrointestinal tract determined the presence of positive dynamics in the parameters, which characterize the electrical and motor activities of large intestine for 60 of 66 patients in the principal group (90.9 per cent) and for 12 patients in the additional group. The parameters of our functional investigations are represented in Table 8.

Table 8. Parameters of functional status of large intestine before and after treatment of cologenic constipation.

Parameters studied	Before treatment	After treatment	íîðìà
Electrical activity (mcV)	0.112 ± 0.011	0.162 ± 0.012	0.185 ± 0.004
Motor activity:  -  activity index  -  peristaltic waves (%)	1.022 ± 0.007  5.30   ± 0.92	1.138 ± 0.007  28.31   ± 1.92	1.140 ± 0.003   38.40   ± 2.10

Table 9. Parameters of functional status of large intestine before and after treatment of rectoanal constipation.

Parameters studied	Before treatment	After treatment	Normal
Electrical activity (mcV)	0.151 ± 0.009	0.181 ± 0.011	0.185 ± 0.004
Motor activity:  -  activity index  -  peristaltic waves (%)	1.081 ± 0.005  8.420 ± 1.05	1.131 ± 0.008  35.120 ± 1.75	1.140 ± 0.003   38.40   ± 2.10

The data representated in the tables above indicate a signifant reduction of the background parameters of electrical and motor activities of large intestine for all the patients; after application of the Electronac Normalizer, we noted the regulating effect on the parameters of the functional status of large intestine that was expressed in the increased index of motor activity and persentage of peristaltic waves. In addition, for the patients, who suffered from rectoanal constipation, sensometering showed better rectal sensivity threshold was 28.7 ± 6.8 ml as compared to 39.5 ± 5.6 ml in the background study (normal range from 15 to 20 ml).

As an illustration, we represent below the diagrams of motor activity (Diagram 1) and wave spectrum (Diagram 2) of large intestine for the whole group of patients studied. These diagrams express the following dynamics of motor activity: motor activity index is increased (in average, by 24.6 per cent) together with increased percentage of peristaltic waves and appearance of propulsive contractions.

Diagram 1. Motor activity index of large intestine before and after application of the Electronic Normalizer.



Diargam 2. Wave spectrum of motor activity before and after application of the Electronic Normalizer.h

It is interesting to note that normalization of the motor functional parameters of large intestine continued even after evacuation of the capsule. The characteristic changes were observed in the ratio of motor activity waves; increased percentage of middle- and high-amplitude contractions of peristaltic type. As a result of application of the Electronic Normalizer, for 41 patients (62.3 per cent) we observed normalization of intestinal wall tone and endocavitary pressure.

As a clinical example, we give below the medical history of patient T. (a woman aged 54), who had been suffering from chronic constipation for more than ten years. This patient had complaints for the absence of self-maintained stool, she had applied purgative for a long time, and only cleansing enemas helped her in the recent time. In the course of functional investigation before application of the Electronic Normalization, we discovered strong depression of the motor activity of large intestine (activity index 1.03) on the background of decreased intestinal wall tone - akynetic and atonic type of motor activity. We noted that the motor activity wave spectrum was shifted towards segmentary low-amplitude contractions (see Figure 1a).

After application of the Electronic Normalizer, we observed the self-maintained stool of this patient on the third day without evacuation of the capsule, which was evacuated only during the next defecation on the fourth day. Then the patient retained her self-maintained stool with the frequency of once every one or two days. In the course of functional investigation, we noted a significant increase in motor activity (activity index increased by 45 per cent and achieved 1.54), as well as restored intestinal wall tone and appearance of peristaltic complexes (see Figure 2b). This patient was recommended to apply the second Electronic Normalizer in three months to strengthen the effect achieved.

Figure 1 - Endointestinal pressure record: - (a) before treatment; (b) - after treatment.

For the control group of patients (36 persons), the result of drug therapy were different from the result obtained for the principal group. From 36 patients treated, only 19 patients showed stool normalization, while for 10 patients this effect was not observed earlier than in two weeks after starting treatment, and 9 patients showed the positive effect even later. For the remaining 17 patients, no positive results were achieved at all.

The functional investigations carried out with this group of patients in dynamics confirmed the results of clinical observations.

Table 10. Functional status parameters of large intestine before and after drug therapy.

Parameters studied	Before trearment	After treatment	Normal
Electrical activity (mcV)	0.114 ± 0.012	0.159 ± 0.012	0.185 ± 0.004
Motor activity:  -  activity index  -  peristaltic waves (%)	1.025 ± 0.006  6.20   ± 0.89	1.118 ± 0.008  22.61   ± 1.67	1.140 ± 0.003   38.40   ± 2.10

The parameters of functional status of patients in the control group before treatment were decreased as well as those of patients in the principal group. After our drug therapy, for more than 50 per cent of patients, we observed some improvement of the motor activity parameters of large intestines.

From the comparative analysis of therapeutical results achieved for the principal and control groups, by statistical processing, we determined the following.

Table 11.

Group of patients	Studied effect (result)			Efficiency
	Positive	Negative	Total
Principal	59	7	66	(89.4%)
Control	19	17	36	(52.8%)
Total	78	24	102 (patients)

Absolute risk reduction (ARR) = 36.7

Relative risk (RR) =	59/(59 + 7)	= 1.7
	19/(19 + 17)

Relative risk reduction (RRR) = 69.7

The resulting relative risk reduction (RRR) indicates that the effect is clinically significance (exceeds 50 per cent) after application of the Electronic Normalizer for the principal group of patients.

CONCLUSION

Electrostimulation of gastrointestinal tract using the Electronic Normalizer (EN) is a reasonable with respect to pathogenesis and highly effective method for treatment of diseases of alimentary system. This kind of electrostimulation actively affects the nervous and muscular systems of gastrointestinal tract, regenerates the motor and evacuator functions, as well as promotes improvement of feeling, increases working capasity, and normalizes the psychoemotional status of patients.

We should note that, in accordance with the results of comparative tests performed in the State Research Center of Coloproctology (Russian Federal Ministry of Public Health and Medical Industry) with the similar constructions from other producers, the Electronic Normalizer (EN) produced by ECOMED Research & Production Association is characterized with the highest efficiency and absence of side effects.

The Electronic Normalizer is a strong facility for therapy of various forms of chronic constipation and other diseases of gastrointestinal tract, which became common in recent years in the whole world.

After application of the Electronic Normalizer (EN) for patients, who suffer from deseases of gastrointestinal tract, the strong positive effect was achieved for 89.4 per cent of patients in the whole. Using the opportunity of successive electrostimulation of all the sections in the gastrointestinal tract, we can discover the sections with decreased motor activity that has a great diagnostical value, in addition to its therapeutical effect.

No side or harmful effects were observed after application of the Electronic Normalizer (EN).

On the basis of the facts aforemantioned, we can recommend the Electronic Normalizer (EN) for wide application in practical medicine not only in stationary, but also in ambulatory and home conditions after prior consulting the physician.

For more detailed presentation of the results of our studies for application of the Electronic Normalizer to treatment of chronic constipation for medical public, we think expedient to attract the attention of scientific and medical mass media to wide distribution of this information.