The method of treatment of patients with typhoid fever

 

(57) Abstract:

The invention relates to medicine, in particular for therapy of infectious disease and can be used for the treatment of patients with typhoid fever. A method of treatment of patients with typhoid fever, which allows to restore the functional state of the antioxidant system, immune status, to reduce the frequency of complications and relapses. This along with an antibiotic is administered antioxidant drugs unithiol in combination with ascorbic acid, -tocopherol in the medium therapeutic course doses. 7 table.

The invention relates to medicine, in particular to the treatment of patients with typhoid fever.

Know the use for the treatment of patients with typhoid fever antibiotics in combination with bruchnotifosny vaccine, Vi-antigen bruchnotifozhnykh microbes, immunomodulators and some other means that is the closest analog of the invention.

However, none of the currently existing methods of treatment of patients with typhoid fever does not prevent the development of complications (perforation of the bowel, intestinal bleeding), often resulting in fatal outcomes, and the occurrence of relapses and for apnoe and pathogenetic therapy of typhoid fever. However, the issue of typhoid fever in the world and in our country is far from its final decision. Annually in the world according to who get sick with typhoid fever about 20 million, 0.8 million of this number die. In Russia in an average year is recorded more than 20,000 cases typhoid fever fatal 1.24% of cases, and often people die in the young, active age. The cost of treating one case of typhoid in 1987 was estimated at 955 rubles at the present time, due to inflation, this amount has increased by almost a thousand times. Thus the problem of typhoid fever has a great economic and social value.

To date insufficient attention was paid to the study of the role of non-specific mechanisms in the pathogenesis of infectious diseases, including typhoid fever. Meanwhile, there are many facts about that in cells and tissues exposed to different nature of extreme stress dramatically increases the intensity of free radical oxidation (CPO). This reduces the protective capacity and activity of antioxidant system (AOS) of the body, neutralizing aggressive free the free radicals and peroxides vital biosubstrates, such as proteins, lipids, nucleic acids, what is the biochemical basis of cellular damage. Found that the number of infectious diseases develops antioxidant deficiency. It contributes to damage of immunocompetent cells and the development of immune dysfunction. Therefore, EPA is now regarded as an extremely important part of the molecular mechanisms of nonspecific resistance of the organism. In typhoid fever the state of AOC so far not been studied. We first established a violation of the functional activity of individual units AOC in patients with typhoid fever during the height of the disease (table.1 and 2). Thus, blood levels of SH-groups of non-protein nature significantly reduced in comparison with the control group. The content of non-protein disulfide SS-groups on the contrary increased, which is reflected in the reduction of size thioldisulfide the factor representing the integral indicator of the redox balance in thioldisulfide link AOC. Therefore, there is a decrease in buffer capacity of the AOC in its most important functional link. Shifts the equilibrium in this link AOC lead to radical perfectively many enzymes, including enzymes of the antioxidative system. Oxidative changes in disulfide system can cause the disruption of blood coagulation, hormonal regulation of vascular tone, structure, and permeability of the membranes of the capillary endothelium.

In addition to the violations in nonenzymatic link AOC in patients with typhoid fever revealed changes in the activity of antioxidant enzymes (table.1 and 2). The disease is accompanied by a significant inhibition of superoxide dismutase (SOD). The decrease of SOD activity may be the cause of increasing concentrations in cells and tissues of the body concentration of superoxidedismutase and the intensification of the SRO. There was also a reduction in the activity of catalase in the blood, which is a significant step in the pathogenesis of the disease. Catalase breaks down hydrogen peroxide (H2ABOUT2), the increasing concentration of H2ABOUT2in the cell can be one of the causes of damage. Accumulation in the tissues of hydrogen peroxide is accompanied by increased chemiluminescence that is revealed in our research. The above testifies to the growing process of the SRO and the development of antioxidant deficiency in patients with typhoid fever.

The essence of izopet what about the treatment, including antibiotics, anti-oxidant therapy.

On the background of treatment with antibiotics, such as Levomycetinum, introduced the following set of antioxidant agents: 5% solution of unithiol 0.1 ml per 1 kg of body weight 2 times a day, 5% solution of ascorbic acid at the rate of 1 ml 2.5-3.5 ml of unithiol 2 times a day. In addition, input/m 10% solution-tocopherol acetate and 1 ml 2 times a day.

Know the use of unithiol, ascorbic acid and-tocopherol alone and in combination for antioxidant therapy. The presence in the molecule of unithiol two sulfhydryl groups with weak coupling S-H and mobile hydrogen atom gives its antioxidant properties. The drug improves the level of thiols: the concentration of endogenous low molecular weight thiols (regeneration of glutathione), through glutathione, but also directly contributes to the regeneration of ascorbic acid (AK//restore DUCK); activates glyutationreduktazu; able to undergo reductive cleavage of available protein SS-group, on the principle chelate linkages or chelation binds the excess of metals of variable valency, kataliziruemoi the project restored equivalents in non-protein thiol-disulfide and ascorbate redox systems, what contributes to the stabilization of structures: has hydrophilic properties than is possible manifestations of antioxidant activity of the drug both in aqueous and lipid phases of the cell. Pronounced antioxidant properties of ascorbic acid due to the presence in its molecule definaley group (SLEEP=SLEEP). In particular, ascorbic acid protects hemoglobin from oxidation and affects the binding of hemoglobin oxygen restores epinephrine, oxidized in the process, and also increases the oxygen capacity of the blood, prevents a sharp drop in oxygen level in tissues and organs, reduces the total oxygen consumption of the body, is involved in the regulation of membrane permeability. However, it should be emphasized that unithiol and ascorbic acid as a synergist, its antioxidant properties are most manifest when using them in combination.

It is known that a-tocopherol possesses antioxidant properties, acting in the lipid phase, is on the one hand active "trap free radicals, on the other hand reducing agent, peroxide compounds, exhibits synergism with ascorbic acid and uni is by antibiotics. All antioxidant tools introduced/m within 7-10 days.

This method of treatment has been tested in the treatment of 82 patients with typhoid fever. The results of the treatment were compared with those of the 59 identical patients who received only standard therapy (chloramphenicol 0,5x4 times, until the 10th day of normal temperature, symptomatic treatment). The test showed a positive result of this treatment. First of all installed the recovery buffer capacity of the antioxidant system in its most important thioldisulfide link. Antioxidants in the treatment process provided normal functioning of the enzyme part of the antioxidant system.

At the same time more quickly normalized indicators of cellular immunity, in particular the ratio of T helper and T suppressor (PL.3, 4 and 5). Normal immunoglobulin. Decreased level of the CEC and normalized their molecular composition.

The result above was (PL.6) reduce the duration of fever in patients on average 3 days, symptoms of intoxication, on average, 2 days, changes in the cardiovascular system (bradycardia, hypotension) are on average 2 days. Above abusiv (respectively 15.3% and 2.4% of intestinal bleeding of 5.1% and 1.2% (table.7). None of reconvalescent during the year of observation is not registered chronic hosting the causative agent of typhoid fever. At the same time when using standard therapy it is detected in 5.1% of patients.

Thus the proposed method of treatment contributed to the normalization of the functional state of the antioxidant system, indices of cellular and humoral immunity, faster patient recovery, to reduce the terrible life-threatening complications, recurrence of the disease and the formation of chronic bacteria carrier that has a significant socio-economic value.

P R I m e R 1. Patient J. 30 years old, unemployed. He entered the hospital on the 5th day of illness with complaints of fever to 39aboutWith and headache. Sick dire: there was a fever, followed by raising the temperature to 38-39aboutC. Runny nose, cough, bowel dysfunction was not. The high temperature was maintained all the days before admission to the hospital.

Epidemiological history: in the family was ill with typhoid fever son a month before the present illness.

When entering a state of moderate severity. Sluggish, dynamiczny, pale. Skin, mouth clean. Ne the s. A/D 110/60. Vesicular breathing in lungs. The swollen tongue with teeth prints lined with gray bloom, dryish. The abdomen is soft, painless: moderately swollen. Symptom Padalka positive. The liver acts from programarea 2 cm, soft edge. That is palpable spleen. Chair normal. Diuresis is not broken. Meningeal symptoms are not present.

Diagnosis: typhoid fever, medium-heavy form. The hospital continued fever, on the 10th day of the disease appeared resolana skin rash. Blood culture negative, feces on the 11th day of illness allocated S. typhi, rnga with erythrocyte salmonellosis the diagnosticum 9,12 positive in a titer of 1: 1600 on the 24th day of illness.

Blood test on admission: erythrocytes 3,9109g/l, hemoglobin 130 g/l, leukocytes 6,4109g/l, eosinophils 1% stab 36% segmented 31% lymphocytes 30% monocytes 2% erythrocyte sedimentation rate of 3 mm/h

The immunological admission: lymphocytes 34% (1,55109g/l), E-ROCK 36% EAC ROCK 23% OF cells 41% E-act.-ROCK 19% TGF-ROCK 17% TFC ROCK 19% TFF/TPC 0,89; ROCK 19% GC-ROCK 23% incomplete outlet 27% mnohorozmerny ROCK 6% OCT 45% OCT 22% OKT 25% OCT/OCT to 0.88; SD 22 25% JgA 2,31 g/l; JgM 1,05 g/l; JgG of 8.95 g/l; CEC 4.1 g/l, including macromolecular 29% weight 41% melamineware 30% RIA 1,43. Atorino of immunodeficita.

Indicators of the antioxidant system (AOS): the content of nonprotein sulfhydryl groups of 0.62 mm/l, disulfide 1,69 mm/l, TDS 0,37, protein sulfhydryl groups 5,90 mm/l, disulfide 4,11 mm/l, TDS 1,44, SOD inhibition 12,05, catalase 0.21 mm/s, glutathion reductase of 0.90 nm/s,

Treatment: diet, mode, levomycetin 2.0 per day, 5% of unithiol (5 ml), 5% ascorbic acid and 1 ml, and 10% tocopherol acetate and 1 ml 2 times a day intramuscularly, symptomatic drugs.

On a background of treatment temperature normalized on the 5th day from the start of treatment, intoxication symptoms disappeared within a week, the size of the liver returned to normal on day 12, the spleen on day 8, hypotension disappeared on day 10. The blood picture was normal on day 19 of the disease.

The immunological 24 day of illness: lymphocytes 30% (1,93109g/l), E-ROCK 56% EAC ROCK 17% OF cells 27% E-act.-ROCK 28% TGF-ROCK 56% TFC ROCK 16% TFF/TPC 2,5; WITH ROCK 9% GC-ROCK 14% incomplete sockets 11% mnohorozmerny 28% OCT 69% OCT 43% OCT 19% OCT/OCT OF 2.26; SD 21% JgA of 2.45 g/l; JgM 1.28 g/l; JgG of 13.9 g/l; CEC of 2.06 g/l, including macromolecular 45% weight 26% RIA 1,2. Therefore, revealed a strong tendency to normalization of immune homeostasis.

Indicators AOC on the 24th day of hydrilla groups 6,37 mm/l, disulfide 6.50 mm/l, TDS 0,98, SOD inhibition 12,87, catalase and 0.37 mm/s, glutationreductaza to 0.63 nm/s,

Was discharged in good condition on the 36th day of the disease with negative cultures of feces and urine under the supervision of a doctor's office infectious diseases clinic.

P R I m m e R 2. Patient, 42 years of age, a crane operator. He entered the clinic of infectious diseases on the 9th day of illness with complaints of General weakness, raising the temperature to 38-39,5aboutWith, headaches, insomnia, poor appetite. Pain in acute disease began with the rise of temperature up to 7 days. Sent to hospital with a diagnosis of typhoid fever.

Epidemiological anamnesis: the patient from apalachia, uses raw water. Prophylactic vaccination is not received.

Upon admission to the hospital the patient's General condition moderate, pale skin, no rash. Zev mild hyperemia. Heart sounds clean, rhythmic. A/D 110/70 mm RT.article The pulse of 70 beats per minute. Vesicular breathing in lungs. Language is thickened, white furred. Belly swollen, palpation painless. The liver stands out from the edge of a costal arch on 1-2 cm Spleen is palpated. Stool, urination is not broken. Exhibited clinical diag is ary salmonellosis the diagnosticum 9,12 positive in a dilution of 1:800 for 16 day of a disease.

Blood test on admission: erythrocytes 3,71012, hemoglobin 128 g/l, leukocytes 5,7109, eosinophils 1% stab 26% segmented 59% lymphocytes 35% monocytes 3% ESR 3 mm/h

The immunological admission: lymphocytes 35% E=ROCK 35% EAC=ROCK 21% OF cells 44% E-act ROCK 25% TGF-ROCK 17% TFC ROCK 18% TGF-TFC 0,95; WITH ROCK 17% GC-ROCK 22% Auto ROCK 2% incomplete outlet 25% mnohorozmerny ROCK 5% OCT 45% OCT 21% OKT 25% OCT/OCT 0,84; SD 26% JgA to 2.18 g/l; JgM 1.2 g/l; JgG of 9.55 g/l; CEC 3.8 g/l, including macromolecular 25% weight 43% melamineware 32% RIA 1,45.

Indices of antioxidant system: the content of nonprotein sulfhydryl groups of 0.57 mm/l, disulfide 1,31 mm/l, TDS 0,44, protein sulfhydryl groups 4,56 mm/l, disulfide of 8.27 mmol/l, TDS 0,55, SOD 21,63 (% inhibition), catalase 0,42 mm/s, glutationreductaza 1,14 km/s,

Treatment: diet, mode, chloramphenicol 2.0 per day, 5% of unital 5 ml, 5% ascorbic acid at 1.0 and 10% of tocopherol acetate and 1 ml 2 times a day intramuscularly, symptomatic drugs for 10 days.

On the background of the treatment the patient's condition has improved, the temperature was normalized on the 7th day from the start of treatment, during the week gone are the symptoms of intoxication (a goal the action of the spleen, the blood picture was normal on the 17th day of the disease.

The immunological indexes on the 23rd day of illness: lymphocytes 32% E-ROCK 52% EAC ROCK 20% OF cells 28% E-act.-ROCK 28% TFF ROCK 32% TFC ROCK 20% TFF/TPC 1,6; ROCK 13% GC-ROCK 17% incomplete sockets 18% mnohorozmerny ROCK 15% OCT 61% OCT 23% OCT/OCT 1,7; SD 21% JgA 2.4 g/l; JgM 1,32 g/l; CEC 2.65 g/l, including macromolecular 31% 45 weight% melamineware 34% RIA 1,18.

Indices of antioxidant system on the 25th day of the disease: the content of nonprotein sulfhydryl groups of 1.06 mm/l, disulfide 0.66 mm/l, TDS 1,60, protein sulfhydryl groups 5,32 mm/l, disulfide 2,99 mm/l, TDS 1,78, SOD inhibition 33,32, catalase 0.48 mm/s, glutathion reductase 0,65 km/s,

Issued on the 29th day of illness in satisfactory condition with negative cultures of feces and urine under the supervision of a doctor's office infectious diseases clinic.

P R I m e R 3. Patient K. 54 years, engineer. He entered the clinic of infectious diseases on the 16th day of illness with complaints of fever, cough, General weakness, lack of appetite. Ill acutely: increased body temperature up to 39aboutWith that came the aching joints, General weakness. Before admission to the hospital were outpatients with a diagnosis of bronchitis, the be is Petit.

Epidemiological history: in the house where someone is sick, there have been several cases of typhoid. Drinking unboiled water from the tap, said odor from the water. Prophylactic vaccination is not received.

At admission the patient's condition moderate, dinamico, pale. Skin, mouth clean. Peripheral lymph nodes are not enlarged. Pulse 80 beats per minute at 38aboutC. heart sounds are muffled, rhythmic contraction. A/D 150/100 mm RT. Art. In the lungs vesicular breathing. Tongue moist, white furred, thick, with imprints of teeth. The abdomen is soft, painless, swollen. Symptom Padalka positive. The liver acts of the rib for 2 cm, soft edge. That is palpable spleen. Chair normal, diuresis is not broken.

Diagnosis: typhoid fever, a severe form of recurrence. On the 16th day of illness isolated from the blood of S. typhi, rnga with erythrocyte Salmonella diagnosticum 0-1; 9, 12 polojitelnaa dynamics in titers of 1:200; 1:800. On the 31st day of the disease from faeces allocated S. typhi.

Blood test on admission: erythrocytes 3,71012g/l, hemoglobin 126 g/l, leukocytes 6,1109g/l, eosinophils 1% band neutrophils 1% segmented 62% lymphocytes, 3% monocytes 3% ESR 13 mm/h

Treatment diet therapy, chloramphenicol 2.0 per day, detoxification therapy.

On the 3rd day in the hospital, the body temperature returned to normal. Over the next 2 weeks is preserved liver enlargement. Muffled heart sounds And/D 140/100 mm RT.article On the 23rd day of normal temperature General condition of the patient deteriorated. There was a fever, severe dizziness, weakness, nausea, increased temperature up to 39aboutWith next day to the 40aboutC, pulse 100 beats per minute. A/D 100/60 mm RT.article From the blood of the newly allocated S. typhi. Febrile temperature was maintained for 9 days. The General condition of heavy, lethargic, attenchen. The questions are answered reluctantly. Pale, low power. Language is thickened, lined with brown patina, a bit dry. Symptom Padalka positive. The liver acts of by-day normal temperature, antioxidant therapy (5% unital 5,0; 5% ascorbic acid 1,0; 10% -tocopherol 1.0 V/m), detoxification therapy.

The blood test again in the dynamics of red blood cells 3,61012g/l; leukocytes 5,6 x x109g/l; stab neutrophils 20% segmented 36% lymphocytes 40% monocytes 3% erythrocyte sedimentation rate of 7 mm/h

The immunological 60-day sickness: lymphocytes 35% E-ROCK 43% EAC-ROCK 21% OF cells 35% E-act.-ROCK 24% TGF-ROCK 24% TFC ROCK 19% TFF/TPC 1,26; ROCK 15% GC-ROCK 21% JgA to 2.18 g/l; JgM 1,33 g/l; JgG 10.2 g/l; CEC 3.1 g/l, including macromolecular 28% weight 46% melamineware 26% RIA 1,35.

Indices of antioxidant system: the content of nonprotein sulfhydryl groups 0,92 mm/l, disulfide 1,09 mm/l, TDS 0,84, protein sulfhydryl groups 6,86 mm/l, disulfide to 8.57 mmol/l, TDS 0,80, SOD inhibition 12,32, catalase 0.28 mm/s, glutathion reductase of 0.45 nm/s,

On the background of the treatment the patient's condition is satisfactory. Recovery. Bacteriological examination of feces, urine negative. Discharged at the 67th day of the disease under the supervision of a doctor's office infectious diseases clinic.

The METHOD of TREATMENT of PATIENTS with TYPHOID fever by adjuvant therapy, including antibiotics,slotow and tocopherol acetate in therapeutic doses.

 

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