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العنوان
Clinical & experimental study of organophosphates and carbamates Induced toxicities /
المؤلف
Hussein, Asmaa Yasseen Abd El Khalek.
هيئة الاعداد
باحث / Asmaa Yasseen Abd El Khalek Hussein
مشرف / Marcelle Ramsis Haroun
مشرف / Mohamed Kamel Ahmed
مشرف / Samia Ahmed Youssif
مشرف / Mohamed Fared Ebraheim
الموضوع
Clinical toxicology.
تاريخ النشر
2013.
عدد الصفحات
365 p. ;
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
علم الأمراض والطب الشرعي
تاريخ الإجازة
1/1/2013
مكان الإجازة
جامعة بنها - كلية طب بشري - طب شرعى
الفهرس
Only 14 pages are availabe for public view

from 385

from 385

Abstract

Organophosphates (OP) and carbamates (CM) compounds are the most common cause of acute pesticide intoxication, and share a common mechanism of toxicity- cholinesterase inhibition.
The widespread use of carbamates and organophosphates as household pesticides and the lack of adequate regulations controlling their sale and applications have encouraged teenagers to prefer them as a modality of attempted suicide. This source of poisoning has become a major health problem in some developing countries.
Organophosphates toxicity affects many organs, including the pancreas, liver and heart. N-methyl carbamates share the capacity to inhibit cholinesterase enzymes with organophosphates and therefore share similar symptomatology during acute and chronic exposures.
The present work was designed to study and describe the epidemiological features of the patients with acute OP &CM poisoning who were admitted to Banha Poisoning Control Unit (BPCU) and also to evaluate the hepatic, renal, pancreatic and cardiac abnormalities that occurs in a selected group of patients with these poisonings and confirmed that experimentally.
-Therefore to fulfill the aim of this work; the present work was designed to conduct a study on both human (clinical) and animal (experimental).
(I)Clinical Study:
It was conducted on the patients of both sexes and different age groups with acute intoxication by the different anticholinesterase compounds { organophosphorus compounds (OPC) & carbamates compounds (CMC)}, who were admitted to BPCU, Banha University Hospitals, Kaluiobia, Egypt, during the period of the study in which the included cases were subjected to epidemiological, clinical and investigational studies.
(II) Experimental study; which carried out on albino rats to confirm the underlying effect of acute OP &CM poisoning on different organs (liver, kidney, pancreas and heart).
-The results obtained from the current study have revealed the following:
(I)Clinical Study
1- Epidemiological Results;
-The interpretation of the analysis of epidemiological data illustrated the following;
(1) Incidence of acute anticholinestrase pesticide poisoning have constituted (16.3%) of all the total intoxicated cases that were admitted to BPCU during the period of the study with prevalence of OPC which represent (66.4%) of total anticholinesterase agents.
(2) The mean age of the patient’s was (19.26) years with range (1-60 years) and the highest frequency (81.9%) was occurred in the age group equal or less than 29 years old with commonest age group were (10-19 years) represent (29.5%), followed by equal distribution of the age (<10 & 20-29 years) (26.2%) for each.
(3) The female patients were predominate represent (56.4%) with no significant difference observed in the mean age between male (19.9+ 15.5) and female (18.5 + 11.7).
(4) The attempt suicidal cases were predominance as a manner of poisoning (52.3%) with statistically significant differences in distribution of the studied group according to the manner of exposure and both of age groups & sex in which attempt suicidal was commonest among female in 2nd and 3rd decade {from 10 to 19 years old (43.6%) and age group 20 to 29 years old (42.3%)}.Meaning while accidental manner of poisoning represents (47.7%) & was common among male patients of age group under 10 years old (54.9%).
(5) Regarding to occupation; there was higher prevalence among students patients (42.3%).
(6) The intoxicated patients from rural area areas were predominant (71.8%) and indoor (household OP & CM) exposure was showed higher prevalence represent (83.9%).
(7) There was higher prevalence of single patients (72.5%).
(8) The ingestion was the predominant rout of exposure (75.2 %).
(9) About 43.6% were admitted to the hospital within one hour of exposure.
(10) There was seasonal variation with summer being the commonest season (59.1%) in which cases was received.
(11) About 87.9% of the OP & CM intoxicated had not received any prehospital treatment measures and The majority of OP& CM intoxicated cases had no past medical history of diseases (89.9%) . no past history of previous exposure was found in (87.9%).
(12) Most of the studied cases were admitted to the inpatient ward (73.9%) followed by those observed in emergency room without admission (22.1%), then intensive care unit (ICU) admitted patients and referred to Ain shams PCC, due to unavailability of either the specific antidotes or the ICU admission places each of which (2.0%).
(13) The majority of the studied intoxicated cases had full recovery outcomes (79.9%) & only one case with (OPC) had died (0.7%), mainly due to complications of post-anoxic encephalopathy & multiple organs failure (MOFs).
(14)Comparison between CMC & OPC Intoxicated Cases regarding to epidemiological characters showed that; among the OPC intoxicated cases, the age group (< 10) years (31.3%) & accidental manner (63.6%) were the predominated epidemiological features. On the hand the age group (10-19) years (44.0 %) & suicidal manner (84.0%) were the predominated epidemiological features among the CMC intoxicated cases. Meanwhile the other epidemiological features were almost similar and predominated in both the OP and CM intoxicated cases: female (51.5%, 66.0 respectively), rural residence (74.7%, 66.0% respectively), indoor as a place of poisoning (76.8%, 98.0% respectively), and oral route of exposure (63.6%, 98.0% respectively).
2- Clinical examination Study
A) Clinical presentation:
-Regarding to the positive clinical examination findings the results of the present study illustrated the following:
(1) Tachycardia and hypertension was the commonest pulse and blood pressure abnormalities presented in (23.5% & 12.1% respectively).
(2) nausea & vomiting was the commonest clinical presentation found in 103 cases (69.1%) followed by meiosis & abdominal pain which presented in 90 cases (60.4% for each one), increases body secretions (47%), equal distribution of both fasciculations & diarrhea (34.9%), urine incontinence (24.8%), muscle weakness (18.15%) and pulmonary edema (10.1%). There were significant differences in the clinical presentation between the OP and CM intoxicated cases in muscle (OP = 24.2% and CM = 6.0%).
B) Severity of poisoning (PSS) and Glasgow coma scale (GCS):
1- The assessments of severity of poisoning (PSS) show that mild cases (PSS = 1) were predominate found in (43.0%).
2- The mean of GCS found to be (13.79 + 1.4) with (47.66%) of the patients were full awake with GCS (15); (43.62%) of the patients Drowsy with GCS (12-14) and (8.72%) of the patients in Stupor or coma with GCS (3-11) with significant difference between OP &CM studied case regarding to the mean of GCS (13.5 and 14.2 respectively) .
3-There was significant negative correlation between the degree of severity of poisoning and Glasgow coma scale (GCS) scores among the OP &CM studied cases. Meaning while there was significant positive correlation between the degree of severity of poisoning (PSS) and time of delay among both OP & CM studied intoxicated cases. Also, there was significant relation between outcome & Glasgow coma scale (GCS) (P< 0.001).
C) Lines of treatment:
Gastric lavage & Activated charcoal were the most common decontamination measures done in (38.9%). Atropine was given to 129 cases (86.6%) while oximes (PAM) were given only to 54 cases (36.2%).
The differences in the treatment lines between OP and CM intoxicated cases were found regarding to both decontamination measures and Oximes therapy in which; the main decontaminating methods in OPP were gastric lavage and activated charcoal (48.5%); while in CM poisoning syrup of Ipecac and activated charcoal was the main decontaminating method in (70.0%). Also, oximes therapy showed significant difference (p <0.001) between OP and CM, as in OP oximes therapy was used in (49.5%); meanwhile it was used only in 5 cases (10.0%) of CM cases.
1- Investigational Study
A-Biochemical Human Study:
The results of the present study illustrated statistically highly significant reduction in butyrylcholinesterase (BuChE) levels. The pattern of reduction in Butyrylcholinesterase (BuChE) levels was as follows: 16.1 % of cases had ”normal level”, 23.2 % of cases were ”50%-100% of the laboratory minimum normal value”, 28.6 % of cases were ”20%-50%”, 17.9 % of cases were ”10%-20%” and 14.3 % of cases were ”< 10% of the laboratory minimum normal value”.
There were (41.1 %) of OP &CM intoxicated cases had ”elevated blood glucose; (26.8 %) had acidosis (either respiratory or metabolic) and (33.9%) had “hypokalemia”. The decreased k level show statistically highly significant (P<0.001) difference when compared to control volunteers, meaning while the elevated level of blood glucose level were statistically insignificant compared to volunteer group.
There was a significant negative correlation between the severity of poisoning and both of the mean butyrylcholinesterase (BuChE) levels and K plasma level, meaning while there was a significant positive correlation between the severity of poisoning and both of increased blood glucose level and acidosis.
Among the OP &CM intoxicated cases, AST & ALT was elevated in (33.9% & 30.4 % respectively); elevated urea & creatinin found in (14.3% & 10.7 % respectively) and Serum amylase and lipase were elevated in only 3 patients (represented 5.4% for each of them) , but these elevations were found to be statistically insignificant when compared with control volunteer.
There was a significant positive correlation between the severity of poisoning and each of elevated AST, ALT, urea, creatinin, lipase & amylase.
B-ECG Study:
The Interpretation of the present study results revealed that among the 56 studied cases with proved acute anticholinesterase OP & CM exposure there were; (80.4%) had positive baseline ECG abnormalities with sinus tachycardia being the commonest ECG abnormalities found in (32.1 %) followed by QTc prolongations in (26.8%). The other ECG abnormalities that were recorded in our patient were sinus bradycardia (17.9 %), prolonged PR interval (3.6%), non specific elevated ST segment (3.6%) & (1%) for each of ventricular tachycardia, T wave abnormalities, extra systole & Right bundle branch block.
The mean of QTc interval was (0.41mesc.) with range (0.35-0.55) and all of the patients with prolonged QTc interval show full recovery. No significance difference observed in the outcome regarding to QTc interval duration between patients with normal QTc interval and those with prolonged one.
There was insignificant positive correlation between QTC interval and both of length of stay and severity of poisoning
There was significant positive correlation between QTC interval and severity of poisoning. Meaning while there were significant negative correlation between QTc interval and both of the mean Butyrylcholinesterase (BuChE) levels and K plasma level.
(II)Experimental (Animal) Study:
A-Biochemical Animal Study:
Among DZN &MEM treated groups; the mean pseudocholinestrase activities was significantly decreased when compared with control group, meaning while the mean blood glucose level was significantly higher among DZN &MEM treated groups.
The serum AST, ALT, amylase and lipase enzymes levels were significantly increased in both DZN &MEM treated groups when compared with control group. However, elevation of both blood urea and creatinin level among DZN &MEM treated groups found to be insignificant compared with control group.
B-Histopathological Animal Study:
-The interpretation of the present study has revealed the presence of;
1- Significant histopathological abnormalities in the livers sections of DZN &MEM treated groups compared to control group which includes (cellular degeneration, edema, necrosis, inflammatory cells infiltrates, Kupffer cell proliferation, sinusoidal dilatation & congestion, central vein dilatation and congestion, portal vein dilatation, congestion). Bile duct proliferation were found statistically insignificant
2- Significant renal injury in both DZN &MEM treated groups compared with control group. There were significant presence of tubular degeneration, vacuolization and sloughing of tubular epithelial cells and inflammatory cells infiltrate) which found mainly in proximal tubules.
3- Significant pancreatic injury represented by (edema, inflammation, vacuolization, and necrosis) of varying grades among both acute DZN &MEM treated groups when compared with control groups.
4- Significant myocardial injury among both acute OP & CM treated rat groups when compared with control group including (intracardiac edema, inflammation, congestion, hemorrhage and myocardial degeneration). Also, there were insignificant myocardial necrosis and intracardiac thrombosis among both DZN &MEM treated rat groups.