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PEDIATRICS
INVENTION
Patent of the Russian Federation RU2199358

METHOD FOR TREATMENT OF CHRONIC INFLAMMATORY DISEASES OF URINARY PULMONARY WAYS IN CHILDREN

METHOD FOR TREATMENT OF CHRONIC INFLAMMATORY DISEASES
UTERINE WAYS IN CHILDREN

The name of the inventor: Shilenok IG; S. Nesterov; Tush EV; Voevodkina IF; Rodionova E.I .; Petelina O.Yu.
The name of the patent holder: Nizhny Novgorod State Medical Academy; Shilenok Ivan Grigorievich
Address for correspondence: 603005, Nizhny Novgorod, ul. Alekseevskaya, 1, NGMA, Patent Department
The effective date of the patent: 2001.02.07

The invention relates to medicine, namely pediatrics, and can be used to treat chronic inflammatory diseases of the urinary tract in children. The method is a complex medication therapy, including antibiotics, uroseptics, urinary bladder instillations, membrane stabilizers, phytopreparations, characterized in that antibiotic therapy is carried out 14-21 days by parallel courses of lymphotropic and intramuscular antibiotic administration, with a daily 1/2-day dose of antibiotic administered lymphotropically, Once and the other 1/2 of the daily dose intramuscularly twice, with the lymphotropic administration being performed subcutaneously, alternately to the right and left in the projection of the round ligament of the uterus in the girls and the spermatic cord in the boys, each time being injected sequentially with a drug enhancing the lymph current , Stimulator of microcirculation and then the antibiotic itself. The method allows to increase the duration of remission, to reduce the frequency of relapses, to effectively stop incontinence.

DESCRIPTION OF THE INVENTION

The present invention relates to medicine, namely pediatrics, and can be used to treat chronic inflammatory diseases of the urinary tract in children.

In the last 10-20 years there has been an increase in the morbidity of children with diseases of the urinary system, which are now on the second place after respiratory diseases. So, according to literature data in the 80s, the frequency of diseases of the organs of the urinary system averaged 29 per 1000 with variations in different regions from 12 to 54 per 1,000 children (Ignatova MS, 1989), and according to A.A. . Baranova (1997) over the past five years, their frequency has almost doubled. Among nephro- and uropathies, the main place is occupied by microbial-inflammatory lesions of the urinary system. In the structure of renal pathology for 1988-1997 according to the data of the Tushino Children's Hospital in Moscow (chief physician VF Smirnov), microbial-inflammatory diseases of the urinary system account for 75.6%, and according to the data of the nephrological department of the State Children's Hospital No. 1 in Nizhny Novgorod - 62%.

The number of children is also increasing, in which the process is repeatedly repetitive, resistant to conventional therapy. A significant number of these children against the background of the inflammatory process of the bladder develop urinary disorders, which further violate the social adaptation of children and worsen the quality of life (up to the determination of disability). Considering all the above, it seems necessary to develop a new approach to the treatment of chronic inflammatory diseases of the urinary system.

For the prototype of the invention, a conventional method for the treatment of chronic inflammatory diseases of the urinary tract, including a course of antibiotics (penicillin, cephalosporin, aminoglycoside series) parenterally (intramuscularly, in severe cases intravenously), 7-10 days, appointed based on the results of urine culture and sensitivity to antibiotics Or in the absence of sowing from local data on the most frequent pathogens and their sensitivity to antibiotics, then per os long courses of uroseptics according to the schemes (up to 6 months), courses of membrane stabilizers (essential, demyphosphon, vitamins E, group B) and immunomodulators (methyluracil, nucleate Sodium, tincture of echinacea), phytotherapy (kidney tea, decoction of bilberry leaves, birch buds, cranberry juice, etc.), topically if there are signs of chronic granular cystitis according to cystoscopy and there is no PMR bladder installation with antibacterial drugs (dioxidin, kanamycin) and Cauterizing solutions (collargol, silver nitrate in increasing concentrations from 1: 5000 to 1: 500) [1].

However, treatment of this group of diseases with the above method is successful only in one third of patients, the rest patients require repeated courses of antibacterial therapy with a change of drugs of different spectrum of action [1], in a number of patients the process despite continuous antibacterial and uroseptic therapy takes a continuously recurrent nature . In addition, when antibacterial drugs are administered intramuscularly or intravenously, the drugs are distributed to all organs and tissues and cause a significant xenogeneic load on the body. One should also take into account the fact that a normal urine flow is the key to successful elimination of a pathogenic agent, which is difficult to achieve in the conditions of inflammatory infiltration, edema and hypoenergetic state of the lower urinary tract (due to microcirculatory disturbances) [5]. The duration of remission with the use of the prototype method in a number of patients (combined defeat of the upper and lower urinary tract against the background of abnormal development of renal tissue (dysplasia), bladder innervation disorders) does not exceed 1-3 months, and it is impossible to cancel uroseptics for more than 2 weeks . Insufficient efficiency of the prototype method is also manifested in the fact that after the course of treatment the incontinence frequency in children, although decreased, but not more than 20%, and therefore remained within 5-20 times a day. In addition, children experienced chronic intoxication for a long time (years), decreased physical development, and cystoscopically manifested manifestations of cystitis.

The aim of the present invention is to increase the duration of remission, reduce the recurrence rate of the disease, more effectively stop urinary incontinence, the possibility of canceling uroseptics, and the remission of granular cystitis.

The goal in the treatment of chronic inflammatory diseases of the urinary tract in children, including complex drug therapy (antibiotics, uroseptics, bladder installations, membrane stabilizers, phytopreparations) is achieved in that antibiotic therapy is carried out for 14-21 days by parallel courses of lymphotropic and intramuscular injection Antibiotic, and daily 1/2 of the daily dose of the antibiotic is administered lymphotropically, once, and another 1/2 of the daily dose - intramuscularly twice, with lymphotropic injection administered subcutaneously, alternately right and left in the projection of the round ligament of the uterus in girls and spermatic cord in boys, (For example, lidazum, heparin, dalargin), microcirculation stimulator (trental) and then the antibiotic itself, antibiotic selection is carried out taking into account the sensitivity of the isolated flora to the antibiotic and the absence of a local irritant action in the antibiotic (for example, , Gentamycin, cloforan, cefazolin), lidazum is administered in a dose of 32 units per 2 ml of 0.5% solution of novocaine, heparin in a dose of 0.5 ml (2500 units), trental in a dose of 2.5 ml (50 mg pentoxifylline), dalargin In a dose of 0.5 mg per 1 ml of 0.5% solution of novocaine.

The main distinguishing feature of the proposed method is antibiotic therapy with two parallel courses and the development of the lymphotropic course. Lymphotropic administration of drugs has been used by a number of authors, but with other pathological processes and with the help of technically difficult techniques that are of little use in children's practice and fraught with complications. So [6] and [7] used this type of therapy in the treatment of acute destructive (apostematous) pyelonephritis in adults, but in the first case the drug was administered through a catheterized vessel on the foot, in the second - through the drained operative lymph node. [8] applied this method in the treatment of acute peritonitis in children, injecting drugs through a retroperitoneal microarigator installed. However, the proposed methods are technically difficult to perform, require the availability of a qualified microsurgeon, special catheters, suitable for catheterization and drainage of lymphocytes, labor-intensive care and are of little use in children's practice. [9, 10] suggested injecting drugs into the posterior surface of the tibia, creating a venous stasis for preferential absorption of the drug into the lymphatic system. However, this method is not fully regional and fraught with complications in the form of development of infiltrates.

The proposed method is carried out as follows. The course of treatment includes antibiotic therapy, which is carried out as follows: 14-21 days by parallel courses of lymphotropic and intramuscular antibiotic administration (antibiotic selection is carried out taking into account the sensitivity of the isolated flora to the antibiotic and the absence of a local irritant action in the antibiotic (eg, gentamicin, claforan, cefazolin ), With daily 1/2 of the daily dose of the antibiotic administered lymphotropically, once, and another 1/2 of the daily dose - intramuscularly twice, with lymphotropic injection carried out subcutaneously, alternately right and left in the projection of the round ligament of the uterus in girls and spermatic cord in boys, (For example, lidazum, heparin, dalargin), microcirculation stimulant (trental), lidazum is administered in a dose of 32 units per 2 ml of 0.5% solution of novocaine, heparin in a dose of 0.5 ml 2500 ED), trentalum in a dose of 2.5 ml (50 mg pentoxifylline), dalargin in a dose of 0.5 mg per 1 ml of 0.5% solution of novocaine. Then, for 6 months, uroseptic therapy was carried out according to the scheme: during 2 months continuous uroseptics in a full age dose of 2 weeks each (furagin, blacks, palyn, grahamrin, nitroxoline, etc.), then the same uroseptics in a single dose for Night for 1 month each, parallel to membrane stabilizers 2 weeks once a quarter (with hyperoxaluria) - demyphosphon, pyridoxine, trental per os, phytotherapy (renal tea, decoction of bilberry leaf, birch buds, cranberry mors etc.), locally with chronic granular cystitis and Absence of PMR instillation of the bladder with antibacterial drugs (dioxidin, kanamycin) and cauterizing solutions (collargol, silver nitrate in increasing concentrations from 1: 5000 to 1: 500) 1 time per quarter.

The method of lymphotropic antibacterial therapy involves the introduction into the subcutaneous tissue in the projection of the circular ligament of the uterus in girls and the spermatic cord in boys (being the projection zone of inguinal lymph nodes regional to the bladder, the renal tissue penetrates retrograde through the collaterals between the lymph nodes by inguinal, retroperitoneal , Perineal) alternately on the right and on the left (considering that the chronic inflammatory process is bilateral, although in most cases one side is more affected) through the needle from a disposable syringe with a capacity of 5 ml (manufactured by Luer or similar, choice is due to availability) at the beginning The first syringe) of the conductor-lidase at the rate of 32 units (causing a narrowing of lymphatic vessels in this dosage according to experimental data of a number of authors, an increase in the frequency and amplitude of lymphangia pulsations, lymphatic drainage acceleration up to 5.6 times) per 2 ml of 0.5% solution of novocaine Effectively reducing the pain at manipulation, suppressing the pulsation of lymphangia) or in the presence of allergic reactions to lidase-heparin (0.5 ml) (increases the movement of fluid and low molecular weight drugs into the lymphatic capillaries, activates tissue fibrinolysin and increases the accessibility of the environment for diffusion of molecules, Accelerates the lymph flow by 1.5 times), then through the same needle with another syringe (to avoid interaction of drugs on the syringe wall) - trental 2.5 ml (dilates microvessels, inhibits platelet and erythrocyte aggregation, strengthens fibrinolysis and reduces blood viscosity, improving Microcirculation), then, after 2 minutes (a break is necessary for absorption of injected drugs), through the same needle with a third syringe (to avoid interaction of drugs on the syringe wall) - an antibiotic (gentamycin, claforan, cefazolin, taking into account the sensitivity of the isolated flora to antibiotics) in 1/2 of the daily dosage (given that lymphotropic administration of the drug leads to a prolonged, up to a day, preservation of the injected drug in the lymphatic system in growth inhibitory microorganisms) on a 0.5% solution of novocaine. Introductions lasted 14-21 days (assuming that microorganisms cease excreted in excreted urine, persist for a long time in the interstitial tissue of the kidneys and lower urinary tract), in parallel the remaining dose of antibiotic was administered at other times (with lymphotrophic administration at 12 days - 6 And 20 hours respectively) intramuscularly, then the courses of uroseptics according to generally accepted schemes, according to indications membrane stabilizers, instillations, phytotherapy, immunomodulators were not used (according to the data of Kuznika BI lymphotropic therapy itself is able to activate regional immune defense).

The proposed method allows for targeted delivery of the antibacterial drug to the organs of the urinary system (from the subcutaneous fat the drug is absorbed into the inguinal lymph nodes, and from them, with a retrograde current of lymph through collaterals penetrates into the wall of the bladder, urinary tracts and into the kidneys, creating high interstitium concentrations ), The absorption of the drug into the lymphatic and not the bloodstream is facilitated by the conductors - lidase, heparin, which increase lymphatic flow. In parallel, they, together with blood circulation improving agents, increase the lymph and blood flow in the affected organ, promote the resolution of stagnant phenomena in the mucous membrane and interstitial tissue, increase the excretion of metabolic pathological products (under the conditions of inflammation), promote resorption of scar and sclerotic changes and repair of the mucosa Urinary tract, providing a comprehensive therapeutic effect.

Examples of specific use of the method are given in the form of extracts from the medical history.

Example 1

LD, 11 years old, IS 5567.

For 8 years, observed for chronic secondary pyelonephritis, chronic granular cystitis, a condition after surgical treatment of left ureteral achalasia in 1993 (anti-reflux plasty according to Gregoire).

A concomitant diagnosis is diffuse neurodermatitis.

In February 1992, the first attack of pyelonephritis with febrile temperature, pronounced leukocyturia, trace proteinuria, in the blood anemia normochromic of mild severity, acceleration of the ESR up to 26 mm / h, in the urine of the growth of Klebsiella 100 million cubic. E., Received therapy: furazolidone 0.2 g / day 4 days (canceled due to development of dyspepsia), phosphomycin 8 days, biseptol-240 10 days, nitroxoline 0.2 g / day 5 days (urticaria), klaforan 900,000 / Day - treatment for 2 months without effect, a significant leucocyturia remained in the urine tests, at home for 10 days furagin 0.15 g / day, a month after discharge from the hospital against the background of furagin (repeated course) increase in leukocyturia to 381 thousand according to Nechiporenko , Treatment in hospital in May-June (gentamicin IM, suspension of phosphomycin, 5-NOK, + melipramine, proserin) and July-August (detoxification drip therapy, unazine IV m 1400 mg / day 10 days, gentamicin 5 days, Nolitsin 800 mg / day 10 days, immunoglobulin in / m 3), in October 1992, a diagnosis of tuberculous papillitis of the left kidney, BK +, is established. Later, after specific antituberculous treatment, BC is resistant to "-", there is no data for activation of the tuberculosis process. In October 1993, surgical treatment of left-sided reflux of grade 3 was performed.

Nonspecific inflammatory process acquired continuously recurrent character (2-3 exacerbations per year), in outpatient analyzes of urine leucocyturia from 3-5 to completely in the field of view, received out-patient furagin, fa-penicillin, gentamicin, phytotherapy.

Hospitalized in May 1997 - (gentamicin, lincomycin, blacks, furagin, actovegin, cavinton, vitamin therapy). In March 1998, - leukocyturia, back pain, staphylococcus epidermal 5 million fu - intravenous drip detoxification, iv fortune 10 days, biseptol, instillations with kanamycin 5, with silver nitrate 5. In April 1998 - in urine fecal streptococcus - netromycin w / m, graham, nigra, instillation with silver nitrate. In December 1998 - lethargy, leukocyturia, 5 million E. coli, - in / m carbenicillin, amikin, inside furagin, lipostabil, instillation with silver. Given the severity of the course of the process, the presence of social maladaptation due to enuresis and encopresis, the girl is diagnosed with disability.

At admission in October 1999, the condition of the disease is severe, the symptoms of chronic intoxication (decreased appetite, pale skin, periorbital cyanosis), severe urination disorders (urinates 2-4 times a day in large volumes, against this background urinary incontinence in small portions - 2 shifts Lingerie per day, urge to urinate, rare enuresis, urodynamic - bladder hyporeflexia), in urinalysis - moderate leukocyturia, isolated by E. coli seeding method in a titer of 1 million cu.

In the trial of Zimnitsky ud. Weight 1010-1021.

On the ultrasound of the kidneys - hypoplasia of the left kidney, with intravenous urography (from January 2000) - there is a deformation of the bowl-left pelvis complex on the left, pathological mobility of the right kidney, non-growth of the L5 arch.

On cystoscopy - the mucosa is pale pink, dotted with a multitude of granules, flakes of fibrin float in the lumen.

Diagnosis: chronic secondary pyelonephritis, against a background of hypoplasia (?) Of the left kidney, stage of exacerbation, without disturbance of renal function.

Chronic granular cystitis, stage of exacerbation.

Hyperreflective urinary bladder. Encopres.

Diffuse neurodermatitis, the stage of exacerbation.

A course of endolymphatic therapy 24 including heparin 0.4 ml, trental 2.5 ml, novocaine 2.0 ml 0.25% solution, gentamicin 60 mg 6, and then klaforan 18 500 mg, followed by the transition to uroseptics. In parallel, antibiotics were administered intramuscularly to a daily dose of gentamicin (4 mg / kg), cloforan (60 mg / kg). Against the background of treatment the urine indicators were normalized, urinary incontinence was stopped.

In a catamnesis after 11 months with a planned hospitalization: the state of moderate severity of the disease, the symptoms of chronic intoxication are less, urine keeps the urine day and night, the regime of compulsory urination (every 2 hours), urodynamically moderate increase in velocity with a large volume of urine, with control cystoscopy There is no residual urine, the mucosa is pale pink, in the region of the bottom 1-2 granules in the stage of reverse development.

Diagnosis at the time of discharge: chronic secondary pyelonephritis, against a background of hypoplasia (?) Of the left kidney, stage of incomplete clinical and laboratory remission, without disturbance of kidney function.

Chronic granular cystitis, stage of remission.

Hyperreflective urinary bladder.

Diffuse neurodermatitis, the stage of remission.

Example 2

Patient S.P., 7 years old.

It has been observed in the nephrologic department of Children's hospital No 1 for 5 years for chronic secondary pyelonephritis against a background of hypoplasia of the right kidney with dysplasia, continuously reninning flow, chronic granular cystitis, hyperreflexive bladder with day and night incontinence, encopresis.

Repeatedly received courses of antibiotics of penicillin, cephalosporin, aminoglycoside series, continuous maintenance therapy with uroseptics, phytopreparations, membrane stabilizers, bladder installations with antibiotics and cauterizing substances. Stubborn persistence of the urinary syndrome (leukocyturia, bacteriuria), sowing of various strains of microorganisms, including Pseudomonas aeruginosa, daily (up to 5 times a day) urinary incontinence, enuresis, urination in small portions up to 20 times a day, in the process of dynamic Observations showed a decrease in the size of the right kidney.

Given the ineffectiveness of traditional therapy, the patient underwent repeated courses of lymphotropic therapy: February 1999 - within 10 days of lidase, trental, netromycin lymphogenically, then 9 days of lidase, trental, cloforan, administration was canceled due to the development of an allergic reaction in the form of urticaria, August 1999 - within 9 days heparin, novocaine, cefanthral lymphogenous, October 1999 - 21 days of lymphotropic cefantral therapy, with 10 days together with heparin, trental, and the next 10 days heparin was replaced with dalargin, while the last hospitalization In the patient with normal general analysis of urine isolated Pseudomonas aeruginosa.

In a catamnesis a year later, there is a remission in chronic pyelonephritis and cystitis (normal urine tests, sterile sowings, significant cystoscopic improvement - single granules in the cervical mucosa, no other changes), urinary incontinence at the end of the last course was not noted, Has now resumed after the beginning of the class in the first grade of the school (the girl does not learn the school curriculum, IQ = 80) 12 episodes in the afternoon and 3-4 episodes of enuresis per week.

This method of treatment was applied in 7 patients, in one patient - twice and in one - three times, in total 9 courses. In a catamnesis positive results were traced in 4 patients, immediate positive effect (relief of the inflammatory process and disorders of urination) was noted in all.

INFORMATION SOURCES

1. Korovina IA, Zakharova IP, Mumladze EB, Zaplatnikov AL Antibacterial therapy of infections of the urinary system in children. (Guide for doctors). - Moscow, 1998.

2. Markova IV, Nezhentsev MB., Papayan A.V. Treatment of kidney diseases in children. - St. Petersburg, 1994. - 400 p.

3. AG Pugachev, SN Eshmukhabetov. Chronic cystitis in children. - Alma-Ata, 1983 - 152 p.

4. Erman MV Nephrology of childhood in the schemes and tables. Reference Guide. - St. Petersburg: Special Literature, 1997. - 414 p.

5. Javad-Zade MD, Derzhavin VM Neurogenic dysfunction of the bladder. M .: Medicine, 1989 - 384 p.

6. Dolgym MR, Slutsky IM, Levitsky E.R. With et al. Endolymphatic antibiotic therapy in the complex treatment of acute pyelonephritis. Urology and nephrology, 1987, 5, p. 11-15.

7. Uhal MI, Lunev RA, Petrovsky Yu.B. Postoperative endolymphatic antibiotic therapy in urological patients with purulent inflammatory diseases. Urology and Nephrology, 1990, 4, p. 17-20.

8. Sultanbaev T.Zh., Levin Yu.M., Dzhenalayev B.K. Lymphotropic antibacterial therapy and stimulation of lymphatic drainage in the complex treatment of peritonitis in children. Clinical Surgery, 1988, 6, p. 43-45.

9. Levin Yu.M., Buyanov VM, Danilov K.Yu. With et al. Lymphotropic antibiotic therapy. Surgery, 1987, 1.

10. Ganieva M. Sh., Efficacy of Indirect Lymphatic Antibiotic Therapy for Acute Pyelonephritis in Children, Diss. Cand. honey. Sciences, 1993.

CLAIM

1. A method for treating chronic urinary tract diseases in children by means of complex medicamentous therapy, including antibiotics, uroseptics, urinary bladder instillations, membrane stabilizers, phytopreparations, characterized in that antibiotic therapy is carried out 14-21 days by parallel courses of lymphotropic and intramuscular antibiotic administration, with daily 1 / 2 daily doses of antibiotic are administered lymphotropically, once, and the other 1/2 of the daily dose is intramuscularly doubled, with lymphotropic administration being performed subcutaneously, alternately to the right and left in the projection of the round ligament of the uterus in girls and the spermatic cord in boys, and in this projection each Once injected sequentially drug that increases lymph flow, a stimulator of microcirculation and then the antibiotic itself.

2. A method according to claim 1, characterized in that the drug that enhances lymph flow is selected from lidase, heparin, dalargin.

3. A method according to claim 1, characterized in that the tricotal stimulator is microcirculation.

4. The method of claim 1, wherein the selection of an antibiotic is made taking into account the sensitivity of the isolated flora to the antibiotic and the absence of a local irritant action in the antibiotic.

5. The method of claim 4, wherein the antibiotic is selected from gentamycin, cloforan, cefazolin.

6. The method of claim 2, wherein the lidase is administered at a dose of 32 units per 2 ml of 0.5% novocaine solution, heparin at a dose of 0.5 ml (2500 U), trentalum at a dose of 2.5 ml (50 mg Pentoxifylline), dalargin in a dose of 0.5 mg per 1 ml of 0.5% solution of novocaine.

print version
Date of publication 06.01.2007gg