RU2495687C1 - Method of treating patients with gastroesophageal reflux disease - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention refers to medicine, namely to gastroenterology, laser therapy. The method involves administering the drugs: a proton pump inhibitor and a prokinetic accompanied by laser therapy. The proton pump inhibitor is presented by Controloc 20 mg 2 times a day. Gaviscon is administered in a dose of 2 tablets 3 times a day daily. Trimedat 200 mg is administered 3 times a day. The laser therapy is differentiated. That involves taking into account a severity of gastroesophageal reflux disease, a degree of manifestation of endothelial dysfunction and a severity of upper gastrointestinal motor dysfunction. The manifestation of endothelial dysfunction is shown by the contents of nitrogen oxide, pro-inflammatory, namely IL-1?, IL-6, TNF-? and anti-inflammatory, namely IL-4 cytokines. The degree of upper gastrointestinal motor dysfunction is shown by a stomach/duodenum ratio Pi/P(i+1). A mild degree of gastroesophageal reflux disease implying the levels of nitrogen oxide 35.2±2.7 mcmole/l and more, IL-1? 1.5±0.3 pg/ml or more, IL-6 1.8±0.8 pg/ml or more, TNF-? 2.78±0.35 pg/ml or more, IL-4 4.4±0.42 pg/ml or less, the ratio Pi/P(i+1) of 11.2±5.6% or less requires 6-7 daily procedures of the intravenous laser blood irradiation. The exposure length is 15 minutes at wave length 0.405 mcm, end face output density 1-1.5 mWt, pulse frequency 80 Hz, in a continuous mode. The moderate or severe gastroesophageal reflux disease with the levels of nitrogen oxide less than 35.2.2±2.7 mcmole/l, IL-1? 1.83±0.3 pg/ml or less, IL-6 1.98±0.8 pg/ml or less, TNF-? 10.04±2.84 pg/ml or less, IL-4 3.15±0.43 pg/ml or more, the ratio Pi/P(i+1) of 12.3±4.8% or more requires 9-10 daily procedures of the intravenous laser blood irradiation. The exposure length is 15 minutes at wave length 0.405 mcm, end face output density 1-1.5 mWt, pulse frequency 80 Hz, in a continuous mode.EFFECT: method reduces the drug-induced load, reduces the length of treatment.3 tbl, 3 ex

Description

The invention relates to medicine, namely to the section "gastroenterology", and for the treatment of patients with gastroesophageal reflux disease.

In the last decade, gastroesophageal reflux disease (GERD) has attracted increased attention.

The importance of studying GERD is due primarily to its widespread prevalence. In the course of epidemiological studies, there has been a steady trend towards an increase in the number of patients suffering from GERD in a number of countries in Europe and North America, Russia.

It was shown that patients with GERD have a lower quality of life than patients with untreated duodenal ulcer, angina pectoris, and arterial hypertension.

It is established that, in turn, GERD is a trigger of a cascade of complex mechanisms leading to the development and progression of coronary heart disease, arterial hypertension, bronchial asthma, is the cause of repeated pneumonia, cancer of the larynx, severe caries, which is an incentive for further study of the problem.

Improving the treatment of patients with GERD continues to be one of the urgent aspects of the problem of gastroenterology. At the same time, the insufficient effectiveness of drug therapy forces specialists to develop new methods of treatment of GERD. The practice of the last 10-12 years has shown the promise of using low-intensity laser radiation (LLLT) in this direction. In the literature there is information about the anti-inflammatory, hypolipidemic and antioxidant effects of LLLT, rheological and microcirculatory effects, stimulation of specific and non-specific immunity factors are noted. But there is still no reliable data on the effect of LLLT on some links in the pathogenesis of GERD. A known method of treating patients with GERD using laser therapy (Smorchkova O.S. Application of combined EHF laser therapy in patients with gastroesophageal reflux disease // Scientific and Medical Bulletin of the Central Chernozem Region. - No. 36. - II quarter. - 2009).

A course of percutaneous laser therapy was conducted using the Matrix apparatus (NPO Space Instrumentation, Moscow), head LO 1, symmetrically affected acupuncture points (St44, CV15, St36). 2 minutes after the end of the laser exposure, EHF-therapy with the LO-EHF-5.6 radiating head (wavelength 5.6 mm, frequency 53.57 GHz) on the epigastric region, the projection of the duodenal bulb and the point of maximum pain, lasting 2 minutes per zone.

The disadvantage of this method of treatment is that when prescribing cutaneous laser therapy, the effect occurs only on the area of the contact zone and, unlike intravenous laser blood irradiation, there is no positive effect on endothelial function, and there is no differentiated approach to the appointment of laser therapy.

The closest set of essential features to the claimed invention is a method of treating patients with gastroesophageal reflux disease using contact laser therapy, taken as a prototype (Nikitin A.V., Smorchkova O.S. “Evaluation of the effectiveness of laser therapy for gastroesophageal reflux disease taking into account follow-up observations ". - Laser medicine. - 2009. - T.13, issue 4, p.17-21), including the use of a proton pump inhibitor gastrosol 20 mg 2 times a day, motilak prokinetics 10 mg 3 times a day ki, percutaneous laser wavelength of 0.89 microns, the pulse frequency 80 Hz, output power 5 W, a course of 10 treatments. Every day during one session, 3 zones were affected - the lower third of the sternum, the epigastric region and the area of the most pronounced pain point, exposure time 2 minutes per zone.

The prototype and the claimed invention has the following essential features: the simultaneous use of drugs: proton pump inhibitor, prokinetics, and laser therapy.

However, the disadvantage of the prototype is that laser therapy is prescribed by the cutaneous method, while intravenous irradiation of the blood does not focus on the laser radiation, but rather on the complex correction of changes in the homeostasis system. Laser therapy is prescribed without taking into account the use of the method to increase the level of anti-inflammatory cytokines, stabilize endothelial dysfunction, restore adequate motor function of the upper gastrointestinal tract and a balanced type of autonomic nervous system in patients with gastroesophageal reflux disease.

The invention is aimed at solving the problem of creating a method for a differentiated approach to the treatment of patients with gastroesophageal reflux disease using intravenous laser irradiation of blood.

The solution to this problem provides a decrease in the frequency of clinical manifestations of gastroesophageal reflux disease, reduces the frequency of exacerbations, provides a positive effect on the pathological processes that occur in the upper gastrointestinal tract, reduces the drug load, and at the same time increases the effectiveness of the drug therapy in the patient and justifies the effectiveness of laser therapy in the complex treatment of patients with gastroesophageal reflux disease, taking into account the most important pathogens genetic links in the development of the disease (impaired motor function of the upper gastrointestinal tract, cytokine status, endothelial function).

To achieve this technical result, the claimed invention of a method for treating patients with gastroesophageal reflux disease includes the following essential features: simultaneous complex use of drugs: a proton pump inhibitor, a drug that regulates the motor function of the gastrointestinal tract, and laser therapy, tablet antacids are additionally used, laser therapy is prescribed differentially depending on the severity of gastroesophageal reflux, the degree is expressed awn of endothelial dysfunction (nitric oxide), the level of pro-inflammatory (IL-1β, IL-6, TNF-α) and anti-inflammatory (IL-4) cytokines, the degree of impaired motor function of the upper gastrointestinal tract (coefficient of comparison of the stomach / duodenum Pi / P (i + 1)), with a mild degree of gastroesophageal reflux, with a level of nitric oxide of 35.2 ± 2.7 μmol / L or more, with a level of IL-1β equal to and more than 1.5 ± 0.3 pg / ml, IL-6, equal to and more than 1.8 ± 0.8 pg / ml, TNF-α, equal to and more than 2.78 ± 0.35 pg / ml, IL-4, equal to and less than 4.4 ± 0.42 pg / ml, with Pi / P (i + 1), equal to and less than 11.2 ± 5.6%, p 6-7 daily procedures of intravenous laser irradiation of blood are carried out for 15 minutes with a wavelength of 0.405 μm, output power at the end of a single-use intravenous fiber 1-1.5 mW, pulse frequency 80 Hz, in continuous mode, with moderate and severe severity, the level of nitrates / nitrites is less than 35.2 ± 2.7 μmol / l, with the level of IL-1β equal to and less than 1.83 ± 0.4 pg / ml, IL-6 equal to and less than 1.98 ± 0.8 pg / ml, TNF-α equal to or less than 10.04 ± 2.84 pg / ml, IL-4 equal to or more than 3.15 ± 0.43 pg / ml, with Pi / P (i + 1), equal and more than 12.3 ± 4.8%, 9-10 daily intravenous procedures are performed nuclear irradiation of blood for 15 minutes with a wavelength of 0.405 microns, an output power at the end of a single-use fiber of 1-1.5 mW, a pulse frequency of 80 Hz, in a continuous mode of radiation.

In relation to the prototype, the claimed invention has the following distinctive features: as a proton pump inhibitor, control 20 mg is used, 1 tablet 2 times a day, before meals, as a drug that regulates the motor function of the gastrointestinal tract, 200 mg trimedate 1 tablet 3 times a day, additionally apply antacids - Gaviscon daily, 2 tons 3 times a day, simultaneously prescribe laser therapy differentially depending on the severity of gastroesophageal reflux, the severity of endo Helial dysfunction (nitric oxide), the level of indicators of pro-inflammatory (IL-1β, IL-6, TNF-α) and anti-inflammatory (IL-4) cytokines, the degree of impaired motor function of the upper gastrointestinal tract (coefficient of comparison of the stomach / duodenum Pi / P (i + 1)), with a mild degree of gastroesophageal reflux, with a level of nitric oxide of 35.2 ± 2.7 μmol / L or more, with a level of IL-1β equal to and more than 1.5 ± 0.3 pg / ml, IL-6, equal and more than 1.8 ± 0.8 pg / ml, TNF-α, equal and more than 2.78 ± 0.35 pg / ml, IL-4, equal and less than 4.4 ± 0 , 42 pg / ml, with Pi / P (i + 1) equal to and less than 11.2 ± 5.6%, carried out 6-7 daily procedures for intravenous laser blood irradiation for 15 minutes with a wavelength of 0.405 μm, output power at the end of a single-use intravenous fiber 1-1.5 mW, pulse frequency 80 Hz, in continuous mode, with moderate and severe severity nitrates / nitrites less than 35.2 ± 2.7 μmol / l, with IL-1β equal to and less than 1.83 ± 0.4 pg / ml, IL-6 equal to and less than 1.98 ± 0.8 pg / ml, TNF-α equal to and less than 10.04 ± 2.84 pg / ml, IL-4 equal to or more than 3.15 ± 0.43 pg / ml, with Pi / P (i + 1) equal to and more than 12.3 ± 4.8%; 9-10 daily intravenous laser procedures are performed on bloating for 15 minutes with a wavelength of 0.405 μm, an output power at the end of a single-use fiber of 1-1.5 mW, a pulse frequency of 80 Hz, in a continuous radiation mode.

The following causal relationship exists between the distinguishing features and the technical result: as a result of using the VLOK-405 method of intravenous laser blood irradiation, a normalizing effect on the dynamics of the indices of the motor function of the stomach and duodenum, an increase in the level of anti-inflammatory cytokines, stabilization of the endothelial and autonomic nervous system functions, the effectiveness of drug therapy is increased, and earlier symptoms are relieved diseases, the quality of treatment increases, the treatment time is reduced.

According to the information available to the authors, the set of essential features characterizing the essence of the claimed invention is not known, which allows us to conclude that the invention meets the criterion of "novelty."

According to the authors, the essence of the claimed invention does not follow explicitly from the known level of medicine, since it does not reveal the above treatment method VLOK-405, which distinguishes the claimed invention from the prototype, which allows us to conclude that its criterion is “inventive step”.

The set of essential features characterizing the essence of the invention, in principle, can be used repeatedly in medicine with obtaining a technical result, which consists in increasing the effectiveness of laser therapy for patients with gastroesophageal reflux disease, which allows us to conclude that the invention meets the criterion of "industrial applicability".

This method is as follows.

All patients with gastroesophageal reflux disease undergo complex drug therapy (proton pump inhibitors, drugs that regulate the motor function of the gastrointestinal tract antacids) with the simultaneous use of a course of intravenous laser therapy.

The proposed method for the treatment of patients with gastroesophageal reflux disease was used in 100 patients, of which 68 were women and 32 were men, the average age was 45.8 ± 8.2. All patients with gastroesophageal reflux disease were randomly divided into two groups: control (30 people) and main (70 people). In the 1st (control) group, traditional drug therapy was used for treatment, patients of the 2nd group (main) along with drug therapy received a course of intravenous laser therapy.

The diagnosis of gastroesophageal reflux disease was established on the basis of complaints, medical history, fibroesophagogastroduodenoscopy and daily monitoring of the esophagus pH. All patients were determined motor function of the stomach and duodenum by peripheral EEG. The Gastroscan-GEM gastroenteromonitor device (NPO Istok, Fryazino, Moscow Region) was used to record the signal. When analyzing the signal by power, we analyzed the ratio coefficient (Pi / P (i + 1)) (%), which is the ratio of the electrical activity of the overlying section to the underlying one.

The course of intravenous laser therapy was carried out using the Matrix-VLOK laser therapy apparatus with a wavelength of 0.405 μm with an output power at the end of a single-use fiber of 1-1.5 mW, a pulse frequency of 80 Hz, a duration of one procedure of 15 minutes, a course of treatment of 10 procedures. Procedures are performed daily with a break on Saturday and Sunday.

In the study of endothelial function, various changes in the level of stable metabolites of NO - nitrates and nitrites (NO _x ) were revealed. Patients were divided into groups with normal, low and high levels of metabolites (NO _x ) (table 1).

Table 1 Changes in NO _x concentration in patients with GERD during laser therapy Group of examined Increased content Normal Reduced content Before treatment After treatment Before treatment After treatment Before treatment After treatment Healthy NO _x (35.2 ± 2.7 μmol / L) main group 49.56 ± 1.52 ^## 36.45 ± 1.35 ** 35.78 ± 0.54 36.05 ± 1.14 28.38 ± 1.53 ^## 35.32 ± 2.16 ** control group 52.32 ± 2.97 ^## 45.32 ± 1.44 35.49 ± 1.22 35.63 ± 0.76 28.42 ± 0.98 ^## 3151 ± 2.84 Healthy NO ₂ (7.4 ± 1.5 μmol / L) main group 12.93 ± 0.24 ^## 8.4 ± 0.41 ** 6.38 ± 0.29 8.71 ± 0.52 5.25 ± 0.41 ^# 7.87 ± 1.32 ** control group 11.98 ± 1.6 ^## 11.53 ± 0.61 6.82 ± 0.31 7.3 ± 1.4 5.39 ± 0.64 ^# 6.04 ± 1.133 Healthy NO ₃ = NO _x -NO ₂ (27.8 ± 4.2 μmol / L) main group 36.63 ± 2.57 ^# 28.05 ± 2.67 ** 29.4 ± 0.82 ^# 27.34 ± 2.17 23.13 ± 0.95 ^# 27.45 ± 2.46 ** control group 40.34 ± 3.22 ^# 33.79 ± 2.43 28.67 ± 0.94 ^# 28.33 ± 2.49 23.03 ± 1.24 ^# 25.47 ± 1.98 * p <0.05; ** p <0.01 - differences before and after treatment within the same group ^# p <0.05;^## p <0.01 - differences with healthy

In the main group, the NO _x level was distributed as follows: 48.6% (34 patients) with a reduced content; 27.1% (19 patients) with elevated and 24.3% (17 patients) with normal.

In the control group, the distribution of NO _x was as follows: 53.3% (16 patients) with a reduced content; 30% (9 patients) with elevated and 16.7% (5 patients) with normal. Thus, in both groups of patients with GERD, 3 types of responses of NO generation systems were revealed: a) increased NO synthesis; b) a decrease in the synthesis of NO; c) lack of changes.

Numerous studies have shown that NO plays an important role as an endogenous regulator of vascular tone. Damage and dysfunction of the endothelium lead to a decrease in NO production. This is consistent with our data, as Among our patients with GERD, patients with a low content of NO _x prevailed. Analyzing the above data, we found that under the influence of treatment there were changes both in the main group and in the control group. In patients in the main group with initially reduced NO production, it was revealed that the level of its metabolites significantly increased and reached normal values. Thus, the NO _x level changed from 28.38 ± 1.53 μmol / L to 35.32 ± 2.16 μmol / L (p <0.01), nitrite - from 5.25 ± 0.41 μmol / L to 7.87 ± 1.32 μmol / L (p <0.01), nitrates - from 23.13 ± 0.95 μmol / L to 27.45 ± 2.46 μmol / L (p <0.01). The control group showed an increase in similar indicators, but it was not reliable enough and was not accompanied by the achievement of healthy individuals. The level of NO _x increased from 30.42 ± 0.98 μmol / L to 31.51 ± 2.84 μmol / L (p> 0.05), nitrates - from 23.03 ± 1.24 μmol / L to 25, 47 ± 1.48 μmol / L (p> 0.05), nitrites - from 5.29 ± 0.54 μmol / L to 5.84 ± 1.43 μmol / L (p> 0.05), but the degree growth was much less than in the main group.

Although the system for the synthesis and release of NO by endothelium has significant reserve potentials, an increase in NO production can be no less a dangerous damaging factor than its deficiency. Excess NO increases vascular permeability, has a direct cardiotoxic effect, and leads to persistent generalized vasodilation. In the main group of patients with an initially high content of NO, there was a significant decrease to normal values of NO _x from 49.56 ± 1.52 μmol / L to 36.45 ± 1.35 μmol / L (p <0.01), nitrates from 36 , 63 ± 2.57 μmol / L to 28.05 ± 2.67 μmol / L (p <0.001) and nitrites from 12.93 ± 0.24 μmol / L to 8.4 ± 0.41 μmol / L ( p <0.001). In the group of patients receiving only drug therapy, there was also a decrease in NO _x from 52.32 ± 2.97 μmol / L to 45.32 ± 1.44 μmol / L (p> 0.05), nitrates from 40.34 ± 3.22 μmol / L to 33.79 ± 2.43 μmol / L (p> 0.05) and nitrites from 11.98 ± 1.6 μmol / L to 11.53 ± 0.61 μmol / L (p > 0.05), but it is statistically insignificant and does not reach the norm. At the initially normal level of stable metabolites after treatment, no significant changes occurred in both groups. The level of NO _x in the main group was 35.78 ± 0.54 μmol / L (p> 0.05) and 36.05 ± 1.14 μmol / L (p> 0.05), remaining within the normal range. Along with this, the nitrite level increased from 6.38 ± 0.29 μmol / L to 8.71 ± 0.52 μmol / L (p> 0.05) in the main group and from 6.82 ± 0.31 μmol / L to 7.3 ± 1.4 μmol / L (p> 0.05) in the control group, and nitrate slightly decreased from 29.4 ± 0.82 μmol / L to 27.34 ± 2.17 μmol / L (p > 0.05) and from 28.67 ± 0.94 μmol / L to 28.33 ± 2.49 μmol / L (p> 0.05), respectively.

Thus, the results of our study indicate that the traditional drug therapy of patients with GERD is not accompanied by a significant improvement in the plasma content of stable NO metabolites, while in patients who received laser therapy in addition to drug therapy, we noted a significant improvement in the results as with the initially increased content and at the initially decreased the content of NO _x, an increasing number of patients with normal NO _x, in the study group, in contrast to the patients, receiving only drug therapy.

Based on the foregoing, it can be concluded that the inclusion of laser therapy in the treatment of patients with GERD improves the NO-producing function of the endothelium, which indicates the ability of laser radiation to improve the functional state of the vascular endothelium. Compensation of NO deficiency with the therapy leads to global protection of the body from the damaging effects of free radicals, and a decrease in the severity of oxidative stress.

In our study, we also studied the content of cytokines and the possible effect of LLLT on the cytokine system, since cytokines are most actively involved in the launch of the inflammatory-regenerative cascade, restoration and regeneration of the epithelial layer.

The dynamics of changes in the content of anti-inflammatory (IL-4) and pro-inflammatory (IL-1β, IL-6, TNF-α) cytokines in the blood plasma of patients with GERD are presented in table 2.

table 2 The dynamics of the cytokine content in patients with GERD under the influence of laser radiation Test indicator TNF-α IL-4 IL-6 IL-1β Norm 2.78 ± 0.35 pg / ml 4.4 ± 0.42 pg / ml. 1.8 ± 0.8 pg / ml 1.5 ± 0.3 pg / ml Before treatment After treatment Before treatment After treatment Before treatment After treatment Before treatment After treatment The main column 7.3 ± 1.3 ^# 3.8 ± 1.4 3.3 ± 1.27 4.5 ± 0.9 3.85 ± 0.7 ^# 1.9 ± 0.8 ^* 4.7 ± 0.78 ^## 1.6 ± 0.57 ^* Control gr 7.04 ± 1.2 ^## 5.9 ± 0.8 ^* 3.6 ± 1.36 ^# 4.1 ± 1.3 ^* 3.6 ± 1.9 ^# 2.4 ± 1.7 4.1 ± 0.5 ^## 2.0 ± 0.3 ^** * p <0.05; ** p <0.01 - differences before and after treatment within the same group ^# p <0.05;^## p <0.01 - differences with healthy

As can be seen from table 2, in patients with GERD before treatment, an increase in the level of pro-inflammatory cytokines was noted in comparison with the group of healthy individuals. The level of TNF-α in the main group was 7.3 ± 1.3 pg / ml (p <0.05) in the control group - 7.04 ± 1.2 pg / ml (p <0.01) compared with the healthy group (2.78 ± 0.35 pg / ml). The content of interleukin IL-1β was 4.7 ± 0.78 pg / ml (p <0.01) in the main group and 4.1 ± 0.52 pg / ml (p <0.01) in the control group at a rate of 1 5 ± 0.3 pg / ml. The level of IL-6 was also increased and amounted to 3.85 ± 0.7 pg / ml (p <0.05) in the main group, and 3.6 ± 1.9 pg / ml in the control group (p <0.05) , which is significantly higher than in the group of healthy individuals (1.8 ± 0.8 pg / ml). As for the anti-inflammatory cytokine IL-4, in contrast to the group of healthy individuals, GERD patients showed a significant decrease in this indicator, which amounted to 3.3 ± 1.27 pg / ml in the main group and 3.6 ± 1.36 pg in the control group / ml (p <0.05) with a norm of 4.4 ± 0.42 pg / ml.

Thus, we revealed significant shifts in the cytokine system. On the one hand, these changes, apparently, are caused by the influence of etiological factors of GERD, and on the other hand, they themselves can cause the ineffectiveness of therapeutic measures and lead to a protracted course. A pronounced increase in the content of cytokines in peripheral blood is a reflection of the systemic reaction of the body and serves as one of the indicators of the intensity of the immune response, the activity of the inflammatory cascade and the progression of GERD.

After the treatment, only in the group of patients receiving in addition to drug laser therapy, there was a significant positive trend. Thus, the TNF-α index increased before treatment in the main group significantly decreased and amounted to 3.8 ± 1.4 pg / ml. The observed increase in IL-1β significantly achieved a decrease of 1.6 ± 0.57 pg / ml (p <0.05). The initially increased pro-inflammatory cytokine IL-6 in the main group decreased to 1.9 ± 0.8 pg / ml (p <0.05). Also in the main group, one can observe an increase from the initial level of the anti-inflammatory cytokine IL-4 to 4.5 ± 0.9 pg / ml.

In the group of patients receiving only drug therapy, there was a positive trend, but it did not reach the norm: TNF-α was 5.9 ± 0.8 pg / ml (p <0.05), IL-1β decreased to 2.0 ± 0.3 pg / ml (p <0.01), IL-6 reached 2.4 ± 1.7 pg / ml, there was also a moderate increase in the anti-inflammatory cytokine IL-4 to 4.1 ± 1.3 pg / ml (p <0.01).

Analysis of the content of cytokines before and after treatment in the group of patients with GERD receiving combination therapy revealed a significant decrease in anti-inflammatory cytokines (IL-1β, IL-6, TNF-α) and an increase in anti-inflammatory (IL-4), compared with the group of patients receiving only drug therapy.

This once again confirms the multidirectional nature of the action of laser radiation, including the role of the immune system in the inflammatory-regenerative cascade.

The effect of low-intensity laser radiation on the motor function of the upper gastrointestinal tract in patients with GERD was studied. Movement-evacuation disorders can act as both the leading pathogenetic factor of GERD and in the form of concomitant disorders that can enhance the effect of other aggressive factors. Evaluation of the motor-evacuation function of the upper gastrointestinal tract revealed several types of motor impairment. In the main group, gastric hyperkinesia was detected in 19 (27.14%) patients, duodenojejunal hypokinesia - in 43 (61.43%) patients, and duodenojejunal hyperkinesia - in 8 (11.43%) cases. In the control group, these indicators were 9 (30%), 17 (56.67%) and 4 (13.33%), respectively.

As can be seen from the data presented in table 3, before treatment in patients of the main group, the electrical activity (EA) of the stomach exceeded the normal level several times and amounted to 28.57 ± 4.7% (p <0.01), EA of the duodenum and jejunum on the contrary, it was reduced and amounted to 0.36 ± 0.14% and 1.74 ± 1.44%, respectively. The rhythm coefficient (K _ritm ) was also changed in comparison with the healthy group: K _{ritm of the} stomach - 8.41 ± 2.41; K _ritm duodenum - 0.57 ± 0.29 (p <0.05); K _{ritm of the} jejunum - 1.27 ± 0.88.

The comparison coefficient of the Pi / P CS (i + 1) significantly exceeded the parameters of healthy people in the stomach / duodenum segment - 79.36 ± 14.47 (p <0.01) and slightly decreased on the segment of duodenum / jejunum - 0.21 ± 0.12.

Patients in the control group had a similar picture: EA of the stomach was 29.47 ± 5.6% (p <0.01), EA of the duodenum - 0.45 ± 0.12% and EA of the jejunum - 1.38 ± 1.24 % K _{ritm of the} stomach - 8.92 ± 2.23; K _ritm duodenum - 0.64 ± 0.38 (p <0.05); K _{ritm of the} jejunum - 1.44 ± 0.81; CS Pi / P (i + 1) on the segment of the stomach / duodenum - 65.48 ± 15.43 (p <0.01) and the segment of duodenum / jejunum - 0.32 ± 0.08.

In the main group, after drug therapy in combination with VLOK, normalization of the motor-evacuation function of the upper gastrointestinal tract (34 patients (48.57%)) occurred due to a decrease in the hyperkinetic state of the stomach, which was detected in 11 (15.71%) patients, a decrease in duodenoejunal hypokinesia to 22 (31.43%) patients and duodenoejunal hyperkinesia in 3 (4.29%) cases. A tendency towards normalization of the above indicators was reliably identified: EA of the stomach was 26.24 ± 4.9% (p <0.01), EA of the duodenum - 1.86 ± 0.13% and EA of the jejunum - 3.37 ± 1.36 % K _{ritm of the} stomach - 7.31 ± 2.32; K _ritm duodenum - 1.24 ± 0.32 (p <0.05); K _{ritm of the} jejunum - 2.68 ± 0.91; CS Pi / P (i + 1) on the segment of the stomach / duodenum - 14.10 ± 15.92 (p <0.01) and the segment of duodenum / jejunum - 0.55 ± 0.11. In the control group, the frequency of motor disorders after treatment did not significantly change, and normal function was detected only in 7 patients (23.33%). In patients receiving only drug therapy, the severity of positive dynamics was not comparable with the main group: EA of the stomach - 27.31 ± 5.4% (p <0.01), EA of the duodenum - 0.87 ± 0.15% and EA of the jejunum - 2.68 ± 1.12%. K _{ritm of the} stomach - 6.22 ± 2.17; K _ritm duodenum - 0.93 ± 0.31 (p 0.05); K _{ritm of the} jejunum - 2.34 ± 0.94; CS Pi / P (i + 1) on the segment of the stomach / duodenum - 31.39 ± 14.26 (p <0.01) and the segment of duodenum / jejunum - 0.33 ± 0.09.

Table 3 Dynamics of the motor function of the upper gastrointestinal tract in patients with GERD during laser therapy Indicator Norm Control group Main group Before treatment After treatment Before treatment After treatment EA P ₁ / P _s Stomach (23.2 ± 4.1) 29.47 ± 5.6 ^## 27.31 ± 5.4 ^** 28.57 ± 4.7 ^## 26.24 ± 4.9 ^** Duodenum (2.1 ± 0.9) 0.45 ± 0.12 0.87 ± 0.15 0.36 ± 0.14 1.86 ± 0.13 Jejunum (3.48 ± 1.67) 1.38 ± 1.24 2.68 ± 1.12 1.74 ± 1.44 3.37 ± 1.36 K _ritm Stomach (5.43 ± 2.2) 8.92 ± 2.23 6.22 ± 2.17 8.41 ± 2.41 7.31 ± 2.32 Duodenum (1.1 ± 0.5) 0.64 ± 0.38 0.93 ± 0.31 0.57 ± 0.29 1.24 ± 0.32 ^* Jejunum (2.94 ± 1.43) 1.44 ± 0.81 2.34 ± 0.94 1.27 ± 0.88 2.68 ± 0.91 CS P _i / P _{(i + 1)} Stomach / duodenum (11.2 ± 5.6) 65.48 ± 15.43 ^## 31.39 ± 14.26 ^* 79.36 ± 14.47 ^## 14.10 ± 15.92 Duodenum / jejunum (0.6 ± 0.17) 0.32 ± 0.08 0.33 ± 0.09 0.21 ± 0.12 0.55 ± 0.11 * p <0.05; ** p <0.01 - differences before and after treatment within the same group ^# p <0.05;^## p <0.01 - differences with healthy

From the data analyzed it follows that the most common violation of the motor function of the upper gastrointestinal tract in patients with GERD is the hypokinetic state of the duodenum and jejunum, which manifested itself in a violation of rhythmic activity and coordination of work in these areas. At the same time, there was a significant decrease in EA of duodenum in the main and control groups before treatment. After treatment, in both the control and the main groups, EA DPK changed significantly, but normalization of the indicator (increase in strength and speed of response) occurred only in the group receiving VLOK and drug therapy.

Thus, from the foregoing, it follows that the anti-inflammatory effect of combination therapy with a course of VLOK-405 is superior to traditional drug therapy.

To illustrate the method of treating patients, including the use of drugs and laser therapy (VLOK-405), as well as the normalizing effect on the endothelial function, on the cytokine system and on the motor function of the upper gastrointestinal tract, we provide a brief extract from the medical history No. 245.

Example 1

Patient A., 56 years old, was admitted on 07.27.11. to the gastroenterological department with complaints of burning pains behind the sternum, aggravating immediately after eating, in the supine position, with the body tilted forward, sour mouth, constant sore throat. The above complaints bothered about two years. I went to the ENT doctor, repeatedly received outpatient treatment for pharyngitis and tonsillitis, but the treatment did not bring relief for long. Then she was referred by an ENT doctor for gastroscopy. With fibroesophagogastroduodenoscopy, gastroesophageal reflux, cardia insufficiency was revealed, and therefore was sent to the gastroenterological department for further examination and treatment.

Objectively: from the side of other organs and systems, pathology was not detected.

In the general analysis of blood, biochemical analysis of blood and general analysis of urine - without pathology.

Ultrasound examination of the hepatobiliary system revealed deformation of the gallbladder.

On FEGDS: cardia failure, erosive esophagitis, gastroesophageal reflux.

In the study of the motor function of the upper gastrointestinal tract, hyperkinetic activity of the stomach and hypokinetic activity of the duodenum and jejunum were observed: EA of the stomach - 28.92%, EA duodenum - 0.41%, EA of the jejunum - 1.27%, K _{ritm of the} stomach - 8, 12; K _{ritm of} duodenum - 0.54; K _{ritm of} jejunum - 1.37; CS Pi / P (i + 1) stomach / duodenum - 70.53, Pi / P (i + 1) duodenum / jejunum - 0.43.

When studying the content of cytokines, a shift was found in favor of pro-inflammatory interleukins: TNF-α - 6.9 pg / ml, IL-1β - 4.5 pg / ml, IL-6 - 2.85 pg / ml, IL-4 - 2, 6 pg / ml.

In the study of nitric oxide, an initially lower content of its metabolites was found: NO _x - 27.48 μmol / L, nitrites - 5.32 μmol / L, nitrates - 22.16 μmol / L.

The patient was given a course of intravenous laser therapy against a background of diet and drug therapy - one session per day, 7 sessions per treatment course. The laser wavelength used is 0.405 μm, the pulse frequency is 80 Hz, and the power is 1-1.5 W. The duration of the procedure is 15 minutes. After completing the course of therapy, according to the patient, the general state of health improved significantly, the pain behind the sternum and throat completely stopped.

After the treatment, there was also a positive dynamics of the motor function of the upper gastrointestinal tract: EA of the stomach - 25.43%, EA duodenum - 1.94%, EA of the jejunum - 3.28%, K _{ritm of the} stomach - 6.18; K _{ritm of} duodenum - 1.57; K _{ritm of} jejunum - 2.96; CS Pi / P (i + 1) stomach / duodenum - 13.12, Pi / P (i + 1) duodenum / jejunum - 0.59. Conclusion: the noted changes indicate the normalization of motor function.

A second study of plasma cytokines showed a shift in favor of anti-inflammatory interleukins: TNF-α - 3.47 pg / ml, IL-1β - 1.92 pg / ml, IL-6 - 1.36 pg / ml, IL- 4 - 4.8 pg / ml.

A repeated study of nitric oxide revealed a normalization of the level of its metabolites: NO _x - 34.32 μmol / L, nitrites - 7.96 μmol / L, nitrates - 26.36 μmol / L.

On FEGDS in dynamics after 3 weeks there were no signs of GERD and erosion in the stomach.

In this clinical example, a case of mild severity of erosive gastroesophageal reflux disease is considered. Examination according to the FEGDS of the esophagus revealed signs of GERD, and additional methods of investigation revealed a violation of the motor function of the upper gastrointestinal tract, endothelial function, which was expressed in a reduced content of nitric oxide metabolites, and an increase in pro-inflammatory cytokines.

During treatment, the normalizing effect of intravenous laser therapy on the motor function of the stomach, duodenum and jejunum, endothelial function and the cytokine system was noted.

Example 2

Patient V., 42 years old (case history No. 525), was admitted to the II therapeutic department of KBSP with complaints of pain behind the sternum, heartburn, painful passage of food when swallowing. She considers herself sick for about 4.5 years, when she began to be bothered by heartburn, then the remaining complaints joined, cardiopulmonary insufficiency was detected on FEGDS, drainage erosive damage to the mucous membrane of the distal esophagus, gastroesophageal reflux.

Objectively: from the side of other organs and systems, pathology was not detected.

In a biochemical blood test: indicators are within normal limits. In the general analysis of blood and urine - without pathology.

An investigation of the plasma content of stable metabolites of nitric oxide (nitrates and nitrites) revealed an increase in the concentration of NO _x - 44.56 μmol / L.

In the study of plasma cytokines, an increase in the pro-inflammatory cytokine - TNF-α to 6.97 pg / ml, an increase in IL-6 - 3.54 pg / ml, a normal IL-1β content of 1.41 pg / ml, a decrease in IL -4 to 2.2 pg / ml.

In the study of the motor function of the upper GEST sections, hyperkinetic activity of the stomach and hypokinetic activity of the duodenum and jejunum were detected: EA of the stomach - 26.98%, EA of the duodenum - 1.95%, EA of the jejunum - 1.53%, K _{ritm of the} stomach - 7, 78; K _{ritm of} duodenum - 1.23; K _{ritm of} jejunum - 1.37; CS Pi / P (i + 1) stomach / duodenum - 13, 84, Pi / P (i + 1) duodenal ulcer / jejunum - 0.89.

A patient was given a course of intravenous laser therapy against a background of diet and drug therapy - one session per day, 10 sessions per treatment course, with a wavelength of 0.405 μm, output power at the end of the optical fiber of 1 mW, for 15 minutes.

After the end of the course of therapy, according to the patient, the general state of health significantly improved, pain and heartburn stopped.

Re-examination results

A repeated study of the plasma cytokines showed a normalization of pro-inflammatory cytokines: TNF-α to 3.2 pg / ml, IL-6 to 2.45 pg / ml, and anti-inflammatory IL-4 to 4.6 pg / ml.

A repeated study of the NO _x plasma content showed a normalization of the NO _x content of 34.83 μmol / L.

A second study revealed normalization of the motor function of the upper gastrointestinal tract: EA of the stomach - 24.67%, EA duodenum - 2.15%, EA of the jejunum - 2.52%, K _{ritm of the} stomach - 5.67; K _{ritm of} duodenum - 1.02, K _{ritm of the} jejunum - 2.36; CS Pi / P (i + 1) stomach / duodenum - 11.47, Pi / P (i + 1) duodenum / jejunum - 0.85.

On FEGDS in the dynamics of signs of GERD was not found.

In this clinical example, a case of moderate severity of erosive gastroesophageal reflux disease is considered. With additional research methods, a violation of the motor function of the upper gastrointestinal tract, endothelial function was revealed, which was expressed in an increased content of nitric oxide metabolites and an increase in pro-inflammatory cytokines.

During treatment, the normalizing effect of intravenous laser therapy on the motor function of the stomach, duodenum and jejunum, endothelial function and the cytokine system was noted.

Example 3 (extract from the medical history No. 759)

Patient B., 52 years old. Suffers from peptic ulcer for 12 years, the last year they began to worry about pain in the heart, not associated with physical exertion and not relieved by taking nitrates. Repeatedly consulted a cardiologist. FEGDS was routinely performed, an ulcer of the esophagus was detected. Received in the gastroenterological department. Upon admission to the hospital, she complained of constant pain in the region of the heart, aggravated by the patient lying down with a low headboard and abdomen.

Objectively: the general condition is satisfactory, hypersthenic physique, skin and visible mucous membranes of usual color, no peripheral edema. Respiratory organs within the physiological norm. The boundaries of relative cardiac dullness are not expanded, auscultatory tones are clear, the rhythm is correct, heart rate is 80 beats. in 1 minute. HELL 130/80 mm Hg, palpation of the abdomen is soft, moderately painful in the epigastric region.

In a biochemical blood test: indicators are within normal limits. In the general analysis of blood and urine - without pathology.

On FEGDS: cardia failure, esophageal ulcer, gastroduodenitis.

In the study of the motor function of the upper gastrointestinal tract, hyperkinetic activity of the stomach and duodenum, hypokinetic activity of the jejunum were observed: EA of the stomach - 27.84%, EA duodenum - 2.93%, EA of the jejunum - 1.32%, K _{ritm of the} stomach - 8 , 67; K _{ritm of} duodenum - 1.79; K _{ritm of} jejunum - 1.37; CS Pi / P (i + 1) stomach / duodenum - 9.50, Pi / P (i + 1) duodenum / jejunum - 2.23.

In the study of nitric oxide, an initially increased content of nitric oxide metabolites was found: NO _x - 48.72 μmol / L, nitrites - 13.64 μmol / L, nitrates - 35.08 μmol / L.

In the study of blood plasma, the prevalence of pro-inflammatory cytokines over anti-inflammatory was found: TNF-α - 6.58 pg / ml, IL-1β - 5.24 pg / ml, IL-6 - 2.93 pg / ml, IL-4 - 1, 6 pg / ml.

A course of intravenous laser therapy was prescribed for 10 days with a wavelength of 0.405 μm, output power at the end of the fiber 1 mW, for 15 minutes. Procedures were performed daily, on Saturday and Sunday. Laser therapy was carried out against the background of the use of medications. By the fifth procedure, the patient noted dullness of the pain, and by the end of the course of therapy the patient had completely stopped the pain syndrome.

Additional post-treatment studies

After treatment, a second examination revealed normalization of the motor function of the upper gastrointestinal tract: EA of the stomach - 25.74%, EA of the duodenum - 1.89%, EA of the jejunum - 2.62%, K _{ritm of the} stomach - 6.21; K _{ritm of} duodenum - 0.96; K _{ritm of} jejunum - 1.37; CS Pi / P (i + 1) stomach / duodenum - 13.61, CS Pi / P (i + 1) duodenum / jejunum - 0.72.

The study of the cytokine system revealed a predominance of anti-inflammatory interleukins over pro-inflammatory: TNF-α - 2.61 pg / ml, IL-1β - 1.82 pg / ml, IL-6 - 1.05 pg / ml, IL-4 - 4, 78 pg / ml.

In the study of nitric oxide, a reduction to normal values of nitric oxide metabolites was found: NO _x - 35.24 μmol / L, nitrites - 7.97 μmol / L, nitrates 27.3 μmol / L.

On FEGDS in dynamics: a picture of esophagitis.

In this clinical example of a severe severity of GERD, disturbances in rhythmic activity and coordination of work in the stomach, areas of the duodenum and jejunum, as well as an imbalance in the inflammatory-regenerative cascade and endothelial function, were revealed.

As can be seen from the above observation, complex treatment using intravenous laser therapy had a beneficial effect on the general condition of the patient, the rate of healing of the ulcer defect in this patient was significantly faster than in the observed patients receiving only drug therapy, the corrective effect on the impaired investigated indicators.

Clinical and laboratory studies of the proposed method for the treatment of patients with gastroesophageal reflux disease, compared with the known method (prototype), showed the effectiveness of the proposed method of treatment, the ability to correct changes that occur with this pathology, improve the results of drug therapy, reduce treatment time.

Claims (1)

A method of treating patients with gastroesophageal reflux disease, which includes the simultaneous complex use of drugs: a proton pump inhibitor, prokinetics, and laser therapy, characterized in that as a proton pump inhibitor, 20 mg control is used 1 tablet 2 times a day, before meals, additionally prescribed trimedate 200 mg, 1 tablet 3 times a day, and also use gaviscon daily, 2 tons 3 times a day, laser therapy is prescribed differentially depending on the severity of gastroesophageal of reflux, the severity of endothelial dysfunction, namely nitric oxide, the level of pro-inflammatory indicators, namely IL-1β, IL-6, TNF-α, and anti-inflammatory, namely IL-4, cytokines, the degree of impaired motor function of the upper gastrointestinal tract of the intestinal tract, namely, the coefficient of comparison of the stomach / duodenum Pi / P (i + 1): with a mild degree of gastroesophageal reflux, with a level of nitric oxide of 35.2 ± 2.7 μmol / l or more, with a level of IL-1β equal to and more than 1.5 ± 0.3 pg / ml, IL-6, equal to and more than 1.8 ± 0.8 pg / ml, TNF-α, equal to and more than 2.78 ± 0.35 p g / ml, IL-4, equal to and less than 4.4 ± 0.42 pg / ml, with Pi / P (i + 1), equal to and less than 11.2 ± 5.6%, 6-7 daily procedures are performed intravenous laser irradiation of blood for 15 minutes with a wavelength of 0.405 μm, output power at the end of a single-use intravenous fiber 1-1.5 mW, a pulse frequency of 80 Hz, in a continuous mode of radiation, with moderate and severe severity, the level of nitric oxide is less than 35, 2 ± 2.7 μmol / L, with a level of IL-1β equal to and less than 1.83 ± 0.4 pg / ml, IL-6 equal to and less than 1.98 ± 0.8 pg / ml, TNF-α equal to and less than 10.04 ± 2.84 pg / ml, IL-4 equal to or more than 3.15 ± 0.43 pg / ml, with Pi / P (i + 1) equal to and more less than 12.3 ± 4.8%, 9-10 daily procedures of intravenous laser blood irradiation are carried out for 15 minutes with a wavelength of 0.405 μm, output power at the end of a single-use fiber 1-1.5 mW, pulse frequency 80 Hz, in continuous mode radiation.