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OBJECTIVE: To increase the effectiveness of combined treatment in patients with rectal cancer and moderate risk of progression based on the concept of polyradiomodification (PRM). MATERIAL AND METHODS: The study included 337 patients with rectal cancer and moderate risk of tumor progression. A short course of radiotherapy (cRT) (5x5 Gy) combined with several radiomodifiers (cRT+PRM) was performed in 147 (43.6%) patients. Other 190 (56.4%) patients underwent cRT. The following radio modifiers were used: three-time application of local microwave hyperthermia (Yacht-3 or Yacht-4 devices), two-time intrarectal delivery of a biopolymer composition with Metronidazole before the 3rd and 5th irradiation sessions and two-week oral administration of Capecitabine (Xeloda) at a daily dose of 2.0 g/m2. Surgery was performed in 4-6 weeks after radiotherapy. RESULTS: CRT+PRM program increased 5-year relapse-free survival up to 81.3% compared to 60.3% after cRT alone (p=0.0003) due to significant reduction of the incidence of cancer recurrence from 8.4% to 0.7% (p=0.0013). More effective local growth control expanded the indications for sphincter-sparing surgery. These procedures were performed in 89.1% and 70.5% of patients, respectively (p=0.00001). In the cRT+PRM group, sphincter-sparing surgery reduced incidence of cancer recurrence from 13.7% to 0.8% (p=0.0110), distant metastases - from 23.9% to 13.7% (p=0.00349). CONCLUSION: Radiomodification in neoadjuvant radiotherapy is justified in patients with moderate risk of tumor progression, improves long-term results and increases the incidence of sphincter-sparing surgery.
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Canal Anal , Neoplasias del Recto , Humanos , Canal Anal/patología , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/prevención & control , Recurrencia Local de Neoplasia/patología , Tratamientos Conservadores del Órgano , Terapia Combinada , Neoplasias del Recto/cirugía , Terapia Neoadyuvante , Resultado del Tratamiento , Estadificación de NeoplasiasRESUMEN
Acute hemorrhoids are the most common reason for referring to coloproctologist in people of working age. In the modern world, food culture and lifestyle are the most prominent factors leading to the risk of hemorrhoids. In the 21st century, it is hard to overestimate an importance of potential employability and active social role regarding socio-economic well-being. This thesis applies to patients suffering from proctological diseases, and those with hemorrhoids prevail among these ones. Minimally invasive treatment and pharmacotherapy defined primary needs of patients, i.e. treatment should be quick, safe and effective. Favorable treatment outcomes are possible only in pathogenetic therapy. In this review, we will define the priorities in effective combined treatment of hemorrhoids.
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Hemorroides , Heptaminol , Humanos , Hemorroides/diagnóstico , Hemorroides/tratamiento farmacológico , Heptaminol/uso terapéutico , Ginkgo biloba , Lidocaína/efectos adversosRESUMEN
AIM: In a retrospective study, we evaluated factors associated with the early development of septic shock in patients with severe COVID-19. MATERIALS AND METHODS: We collected medical records of the intensive care unit patients submitted by the local COVID-19 hospitals across Russia to the Federal Center for the Critical Care at the Sechenov First Moscow State Medical University (Sechenov University). Septic shock in crticially ill patients requiring mechanical ventilation was defined as a need in vasopressors to maintain blood pressure. RESULTS: We studied 1078 patients with severe COVID-19 who were admitted to the intensive care units for respiratory support. There were 611 males and 467 females. The mean age was 61.013.7 years. Five hundred twenty five medical records (48.7%) were received from the Moscow hospitals, 159 (14.7%) from the Moscow region, and 394 (36.5%) from the hospitals located in 58 regions of the Russian Federation. In 613 (56.9%) patients, diagnosis of SARS-CoV-2 infection was confirmed by PCR, and in the other cases it was established on the basis of the clinical picture and the results of the chest CT scan. Septic shock developed in 214 (19.9%) of 1078 patients. In the logistic regression model, the risk of septic shock in patients older than 50 years was higher than in patients of a younger age (OR 2.34; 95% CI 1.533.67; p0.0001). In patients with more severe SARS-CoV-2 infection, there was an increase in the prevalence of cardiovascular diseases, including coronary heart disease and atrial fibrillation, type 2 diabetes and malignant tumors. The risk of septic shock in patients with three or more concomitant diseases was higher than in patients without any concomitant chronic diseases (OR 1.76; 95% CI 1.762.70). CONCLUSION: The risk of septic shock in patients with acute respiratory distress syndrome induced by SARS-CoV-2 is higher in patients older than 50 years with concomitant diseases, although a severe course of the disease is also possible in younger patients without any concomitant disorders.
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COVID-19 , Diabetes Mellitus Tipo 2 , Choque Séptico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Moscú/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Federación de Rusia/epidemiología , SARS-CoV-2 , Choque Séptico/diagnóstico , Choque Séptico/epidemiología , Choque Séptico/etiologíaRESUMEN
This article deal with method of multimodal, opioid-free anesthesia for colorectal surgery in the perioperative period. AIM: To improve the quality of treatment for patients with colorectal cancer using non-opioid anesthesia and analgesia in the perioperative period. MATERIAL AND METHODS: The study included 47 patients who underwent laparoscopic colon surgery. This anesthesia method consists of epidural anesthesia with sevoflurane during surgery end epidural analgesia after surgery. We describe the method of non-opioid anesthesia technics during colorectal surgery. The pain syndrome was evaluated at various time intervals. Harvard standard for monitoring during anesthesia is presented. RESULTS: Opioid-free anesthesia is safety method for colorectal surgery. It was also possible to reduce the incidence of postoperative nausea and vomiting, pain, intestinal paresis, the duration of hospitalization, and rise quality of medical care for patient with colorectal cancer.
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Analgesia Epidural , Anestésicos por Inhalación/administración & dosificación , Colectomía/métodos , Neoplasias Colorrectales/cirugía , Sevoflurano/administración & dosificación , Humanos , Laparoscopía , Periodo Perioperatorio , Resultado del TratamientoRESUMEN
The modern model of inpatient surgical care of private and optimized state/govermental medical institutions allows us to change the paradigm of nosological attachment of the hospital bed to one profile of specialists for an adaptive model, when the wards can be reassigned depending on the needs of the hospital. In such multidisciplinary medical centers with mixed hospital beds without a nominal distinction in the nosological departments, a new therapeutic service is being developed - hospitalists, which provide a consistent curation of hospitalized patients, compensation of chronic therapeutic illnesses with patient's preparation for surgical interventions. Our work describes the experience of Fast Track recovery program with the active participation of a hospitalist in a surgical team, which is a new experience in the practice of Russian colorectal surgery.
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Protocolos Clínicos/normas , Médicos Hospitalarios/organización & administración , Hospitales/normas , Atención Perioperativa/normas , Rol del Médico , Especialidades Quirúrgicas/organización & administración , Competencia Clínica , Hospitalización , Humanos , Modelos Organizacionales , Federación de Rusia , Especialización , Especialidades Quirúrgicas/normasRESUMEN
AIM: To study cerebral autoregulation (CA) in region of the stenotic carotid artery. MATERIAL AND METHODS: The study involved 35 patients with critical stenosis of the carotid arteries, including 24 patients were asymptomatic and 11 patients with symptomatic course. Blood flow velocity in middle cerebral arteries was monitored using Multi Dop X (DWL, Germany) with simultaneous noninvasive systemic blood pressure registration (CNAP, Austria). CA was assessed by calculating the phase shift (PS) between spontaneous oscillations of blood flow velocity and blood pressure within the range of systemic Mayer waves (80-120 mHz). RESULTS: In 18 patients, the CA indicators were in the normal range (PS 1.2±0.3 rad). Seventeen patients, including asymptomatic as well as symptomatic types, had impaired CA (PS 0.2±0.2 rad and 0.3±0.2 rad, respectively). Reconstructive surgery, irrespective of clinical manifestations, led to the significant increase in PS (p<0.001) in the early postoperative period (0.9±0.5 and 0.9±0.3 rad, respectively). CONCLUSION: A significant variability in the cerebrovascular reserve capacity in symptomatic and asymptomatic types of carotid artery stenosis was found. CA can be used in determining the indications for surgical treatment and evaluation of its effectiveness in patients with stenosis of carotid arteries.
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Encéfalo/irrigación sanguínea , Estenosis Carotídea/fisiopatología , Circulación Cerebrovascular , Anciano , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Femenino , Homeostasis , Humanos , Masculino , Persona de Mediana Edad , Arteria Cerebral Media/fisiopatología , Ultrasonografía Doppler TranscranealRESUMEN
AIM: To present early and remote surgical outcomes in patients with locally-advanced right-sided colonic cancer, invasion of pancreatic head and/or duodenal wall. MATERIAL AND METHODS: Early and remote surgical outcomes were analyzed in 27 patients who underwent gastropancreatoduodenectomy combined with right-sided hemicolectomy (ileotransversostomy extirpation) for locally-advanced right-sided colonic cancer. RESULTS: Mean time of surgery was 300 (240-460) minutes, intraoperative blood loss - 2000 (500-7200) ml. Postoperative complications were observed in 15 (55.6%) patients. 3 (11.1%) patients died in early postoperative period. Overall 1-, 3- and 5-year survival was 92.7%, 48% and 36,5% respectively. Median was 33 months. CONCLUSION: Advanced combined surgery for locally-advanced right-sided colonic cancer, invasion of pancreatic head and/or duodenal wall is associated with acceptable incidence of postoperative complications, early and long-term mortality.
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Neoplasias del Colon/cirugía , Neoplasias Duodenales/cirugía , Neoplasias Pancreáticas/cirugía , Colectomía/métodos , Colectomía/mortalidad , Colon/patología , Colon/cirugía , Neoplasias del Colon/patología , Neoplasias Duodenales/patología , Duodeno/patología , Duodeno/cirugía , Gastrectomía/métodos , Gastrectomía/mortalidad , Humanos , Invasividad Neoplásica , Páncreas/patología , Páncreas/cirugía , Neoplasias Pancreáticas/patología , Pancreaticoduodenectomía/métodos , Pancreaticoduodenectomía/mortalidadRESUMEN
During recent decades radiotherapy is the basis, on which it is built a medical complex that is the first-line treatment of patients with squamous cell carcinoma of the anal canal. An increase of overall and disease-free survival and quality of life of patients with squamous cell carcinoma of the anal canal at the present stage of development of a comprehensive medical treatment is largely due to the improvement of technical equipment of radiotherapy departments of oncology clinics. The use of modem linear electron accelerators and systems of computer dosimetric planning to create a 3D program of isodose distribution, diagnostic devices (computed tomography and magnetic resonance imaging) as well as a number of other conditions permit accurate summarizing of proposed dose, reducing of absorbed dose to critical structures, diminishing unplanned interruptions in chemoradiotherapy course by means of modern technologies of conformal radiotherapy (3D CRT, IMRT, VMAT). The paper presents the preliminary results of a comprehensive medical treatment of 14 patients with squamous cell carcinoma of the anal canal.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Ano/radioterapia , Carcinoma de Células Escamosas/radioterapia , Radioterapia Conformacional/métodos , Neoplasias del Ano/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Quimioradioterapia , Supervivencia sin Enfermedad , Fluorouracilo/administración & dosificación , Humanos , Imagenología Tridimensional , Imagen por Resonancia Magnética , Mitomicina/administración & dosificación , Aceleradores de Partículas , Calidad de Vida , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Conformacional/instrumentación , Radioterapia de Intensidad Modulada/métodos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Somatic mutations of KRAS, PIK3CA, and BRAF cause insensitivity of colorectal tumors to therapy with anti-EGFR monoclonal antibodies, necessitating a genetic testing prior to therapy. A biological microchip was developed and validated to allow detection of 19 somatic mutations in KRAS, PIK3CA, and BRAF genes. The method combines LNA-clamp PCR and allele-specific hybridization on a microchip and detects mutant DNA in 100 times wild-type background (1%). A total of 66 DNA samples isolated from colorectal tumors were tested with the biochip. Possible associations between the genetic status of the tumor and the patient's characteristics (age, sex, tumor localization, stage, and TMN) were assessed statistically. KRAS mutations were more common in females (P = 0.02) and in patients with distant metastasis (P = 0.04). Other associations between the presence of mutations and patient characteristics were not observed. The method proved highly sensitive and can be used in oncology to select patients who sensitive to therapy with anti-EGFR monoclonal antibodies.
RESUMEN
The article discusses the possibility of neoadjuvant chemotherapy in colon cancer patients and rectal cancer patients without the additional use of radiation therapy. The possible risks and benefits of such approach are analyzed and the data of available clinical studies are provided.
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Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Terapia Neoadyuvante/métodos , Quimioterapia Adyuvante , Neoplasias del Colon/tratamiento farmacológico , Progresión de la Enfermedad , Humanos , Neoplasias del Recto/tratamiento farmacológico , Factores de RiesgoRESUMEN
Our study included 36 patients with hard fixed rectal tumors (T3, T4) who had received combined treatment at the Center's Clinics. On irrigoscopic evidence, lesions were more than 10 cm long. Radiotherapy was conducted thrice a week, STD of 4 Gy--TTD of 40 Gy; capecitabine, per os, 650 mg/m2 twice a day, days 1-22; oxaliplatin, 50 mg/m2, intravenously, days 3, 10 and 17; metronidazole in polymer composition, intrarectally, 10 mg/m2, twice, days 12 and 17 of radiotherapy; local hyperthermia (the <
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hipertermia Inducida , Metronidazol/uso terapéutico , Terapia Neoadyuvante/métodos , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Neoplasias del Recto/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina , Quimioterapia Adyuvante , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Infusiones Intravenosas , Masculino , Metronidazol/efectos adversos , Persona de Mediana Edad , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Fármacos Sensibilizantes a Radiaciones/efectos adversos , Radioterapia Adyuvante , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Resultado del TratamientoRESUMEN
Colorectal cancer is one of the most common cancers in the world. In our work changes of AKR1B1 and AKR1B10 gene expression levels in colorectal tumors were studied. Their potential diagnostic value was previously shown for several other cancer types. These genes encode aldoso reductases, which belong to the aldo-keto reductases superfamily consisting of enzymes capable to reduce numerous aromatic and aliphatic aldehydes and ketones. They are also involved into retinoid metabolism and cancerogenesis. We have carried out comparative analysis of mRNA levels of AKR1B1 and AKR1B10 genes in paired samples of normal and colorectal tumor tissues using RT-PCR and quantitative PCR. We have shown for the first time the decrease of activity of these genes in colorectal carcinomas. Significant reduction of AKR1B10 mRNA level was detected in the most of tumor samples (88%, 65/74) even at the early stages of malignancy, and in more than 60% of cases this downregulation was much higher than 10 folds. The decrease of AKR1B1 mRNA level was shown in 10% of tumors only. Therefore, we have detected quite different mRNA expression patterns in colorectal cancer for these two structurally similar genes. These data could indicate different functional roles of these two genes in colorectum. The significant decrease of AKR1B10 mRNA in most samples of colorectal cancer could be considered as potential diagnostic marker of this type of cancer.
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Aldehído Reductasa/biosíntesis , Biomarcadores de Tumor/biosíntesis , Neoplasias Colorrectales/enzimología , Regulación hacia Abajo , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Proteínas de Neoplasias/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Aldo-Ceto Reductasas , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Retinoides/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The report discusses our 30-year experience with surgical and combined treatment of rectal cancer. In cases of preoperative radiotherapy, loco-regional frequency of relapse dropped to 9.6% as compared with surgery (16.3%). After preoperative thermoradiotherapy it fell to 4.6%; polyradiomodification - 0.5% (3-year follow-up). Distant metastasis formation rates were: after polyradiomodification--1.5%, radiotherapy--9.6%, and thermo-radiotherapy--6%. Recurrence-free survival rates (3 years) were: polyradiomodification--97.3%, thermo-radiotherapy--75.9%, radiotherapy--71.1%, and surgery--58%. Data on regimens and dosage of polyradiomodification alongside radiation damage for different combinations of treatment are presented.
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Terapia Neoadyuvante/métodos , Recurrencia Local de Neoplasia/prevención & control , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Hipertermia Inducida , Masculino , Persona de Mediana Edad , Radioterapia Adyuvante/métodos , Neoplasias del Recto/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The paper presents an evaluation of the results of surgical and combined treatment received by 961 patients at the Center's Clinics within 28 years. The analysis was based on 3 protocols of prospective randomized study. It dealt with assessment of the end results of surgical and combined treatment for operable rectal cancer using one preoperative hyperfractonated STD of 5-25 Gy. That was combined with local microwave hyperthermia and two radio modifiers--local microwave hyperthermia+intrarectal administration of a preparation containing metronidazolum. Due to the latter factor, the rate of 3-year relapse-free survival rose considerably. Also, loco-regional and distant metastasis incidence was cut down due to superior ablasticity of surgery.
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Neoplasias del Recto/mortalidad , Neoplasias del Recto/terapia , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The purpose of this study was to evaluate dynamics of B-waves' amplitudes (BWA) of blood flow velocity (BFV) in patients with cerebrovascular diseases during endovascular operations. We examined 12 patients with neurovascular pathology during neuroendovascular interventions. Patients were divided into two groups: 1st group (6 cases)--without intraoperative neurological complications, 2nd group (6 cases)--with complications. Bilateral monitoring of BFV in middle cerebral arteries was carried out applying Multi Dop X. To estimate BWA Fourier analysis was used. In the 1st group preoperative BWA on the affected side was 3.9 +/- 0.6 cm/s. Intraoperative (during an access to pathologic formation and its embolisation) BWA increased up to 7.7 +/- 1.1 cm/s (p < 0.05). Postoperative BWA decreased to 4.2 +/- 0.8 cm/s. In the 2nd group the preoperative BWA on the affected side was 9.6 +/- 1.1 cm/s (p < 0.05), thus higher than in the 1st group. Intraoperatively we observed further increase of BWA up to 12.1 +/- 2.6 cm/s, accompanied by occurrence or increase of neurological symptoms. Postoperative BWA decreased to 10.4 +/- 2.9 cm/s, whereas we didn't observe regression of neurological symptoms.
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Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/cirugía , Interpretación de Imagen Asistida por Computador/métodos , Procedimientos Neuroquirúrgicos/métodos , Ultrasonografía Doppler Transcraneal/métodos , Ultrasonografía Intervencional/métodos , Procedimientos Quirúrgicos Vasculares/métodos , Adulto , Prótesis Vascular , Encéfalo/irrigación sanguínea , Encéfalo/cirugía , Circulación Cerebrovascular , Ecoencefalografía/métodos , Embolización Terapéutica/métodos , Femenino , Humanos , Presión Intracraneal , Masculino , Microcirugia/métodos , Persona de Mediana Edad , Atención Perioperativa/métodos , Pronóstico , Resultado del TratamientoRESUMEN
Preoperative dynamic autoregulatory responses in 20 patients considered as candidates for vessel temporal clipping (TC) and/or arterial hypotension (AH) at surgery for aneurysms were studied by the thigh cuff method. Normal autoregulatory responses at a regulation rate (RoR) of 20.4 +/- 2.8%/s were found in 10 patients > 30 days after subarachnoidal hemorrhage (SH) while RoR was 12.5 +/- 2.5%/s in 10 other patients (30 days, grade III WFNS showed autoregulation impairment. TC and/or AH were proceeded in 17 operated patients. One postoperative death was due to pulmonary embolism. Two poor results with persistent neurological disorders at discharge were associated with TC but in 1 patient. This patient had severe vasospasm and the lowest RoR (9%/s). There were no TC and/or AH postoperative complications in other 14 patients. All of them and 3 other patients with direct aneurysm clipping had a fair outcome.
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Encéfalo/irrigación sanguínea , Circulación Cerebrovascular , Aneurisma Intracraneal/cirugía , Procedimientos Neuroquirúrgicos/métodos , Arterias Temporales/cirugía , Procedimientos Quirúrgicos Vasculares/métodos , Homeostasis , Humanos , Hipotensión/etiología , Hipotensión/cirugía , Enfermedades del Sistema Nervioso/etiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Hemorragia Subaracnoidea/etiología , Hemorragia Subaracnoidea/cirugía , Instrumentos Quirúrgicos/efectos adversos , Resultado del TratamientoRESUMEN
Fibronectin is a high-molecular polyfunctional glycoprotein occurring in the majority of the body fluids and tissues. Various investigations have demonstrated that plasma fibronectin levels either fail to change, or increase with longer gestation during a normal pregnancy. The time course of changes in fibronectin levels has been found to become lower in the amniotic fluid during pregnancy, though its physiological role has not been defined in this case. In late gestosis, plasma fibronectin concentrations substantially rises as compared to those observed in normal pregnancy.
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Líquido Amniótico/metabolismo , Fibronectinas/metabolismo , Preeclampsia/metabolismo , Embarazo/metabolismo , Líquido Amniótico/química , Femenino , Fibronectinas/sangre , Fibronectinas/química , Humanos , Preeclampsia/etiología , Tercer Trimestre del EmbarazoRESUMEN
It has been found out, that under exposure to atmospheric discharge from chemical and oil-chemical enterprises school-age, children shown disorganization of the activity of nicotineamidadenindinucleotidediaphorase, cytochrome oxidase, acid and alkaline phosphatase in leucocytes, damage of lysosomal membranes of these cells, changes in erythrocytic system and in blood coagulation, shifts in total body sizes and subskin fat deposition in certain age-sex groups, disturbance in the structure of correlational interrelations of enzymocytochemical, hematological and anthropometric + indices etc. The observed deviations in school-age children health status are considered to be prepathological disturbances.
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Contaminantes Atmosféricos/toxicidad , Industria Química , Eritrocitos/fisiología , Crecimiento/efectos de los fármacos , Leucocitos/enzimología , Petróleo/toxicidad , Adolescente , Azerbaiyán , Niño , Eritrocitos/efectos de los fármacos , Femenino , Humanos , Leucocitos/efectos de los fármacos , Masculino , Población UrbanaRESUMEN
The study was undertaken to analyze correlation of 25 indicators characterizing schoolchildren's health status from the cell level up to the body one. There were established some characteristics of forming inner damaging mechanism appearing in the body because of deviations in children's physical development. Body weight deficiency was characterized by high integration of diverse signs, whereas excessive body weight was accompanied by sharp discoordination of interlevel interaction. Low stature was described by links' desynchronization at the cellular and tissue levels that was accompanied by a rupture of relations of the functional systems of the given order with the body level, here interlevel links were indirectly supported.