Are polymorphisms in metabolism protective or a risk for reduced white blood cell counts in a Chinese population with low occupational benzene exposures?

BACKGROUND: Genetic variations in metabolic enzyme genes may enhance hematotoxicity in benzene-exposed populations. OBJECTIVE: To investigate the association between polymorphisms of metabolism genes and white blood cells (WBCs). METHODS: Three hundred and eighty-five benzene-exposed workers and 220 unexposed indoor workers were recruited in China. We explored the relationship between metabolic enzymes polymorphisms [glutathione S-transferase T1/M1 (GSTT1/M1) null, glutathione S-transferase P1 (GSTP1)rs1695, Cytochrome P450 2E1 (CYP2E1) rs3813867, rs2031920, rs6413432, microsomal epoxide hydrolase (mEH) rs1051740, rs2234922] by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis and WBC. RESULTS: The exposed group had lower WBC counts (P<0·001) than the unexposed group. Increased susceptibility to hematotoxicity, as evidenced by lower WBC counts, was found in workers with null-GSTT1 (P = 0·045), null-GSTM1 (P = 0·030), rs2031920 (P = 0·020), and rs3813867 (P = 0·014) genotypes. White blood cell counts were also lower in workers with null-GSTT1 and null-GSTM after adjusting for age, gender, smoking, and alcohol consumption. CONCLUSION: Null-GSTT1 and null-GSTM1 genotypes and Cytochrome P4502E1 (CYP2E1: rs2031920, rs3813867) may support the hematotoxicity of benzene-exposed workers in China, and we can make use of it to select susceptible population.

Identification of compound heterozygous mutations in the ITGA2B gene in a Chinese patient with Glanzmann thrombasthenia.

BACKGROUND: Glanzmann thrombasthenia (GT) is an autosomal recessive bleeding disorder characterized by the tendency to hemorrhage and the inability of platelets to aggregate in response to agonists. GT is caused by a defect of the platelet glycoprotein IIb/IIIa complex. The objective of this study was to describe the clinical features and the genetic cause of GT in a 6-year-old girl from south China. METHODS: A three-generation family was studied. The proband patient aged 6 years and her parents undertook examinations of platelet counts, blood film, bleeding time, platelet aggregation, and flow cytometry. All coding exons of the ITGA2B and ITGB3 genes were amplified by polymerase chain reaction (PCR), and direct sequencing was performed for mutational screening on the patient and normal controls consisted of 52 healthy blood donors. Reverse transcription PCR was conducted to test for exon skipping. RESULTS: The proposita patient showed dispersing platelets, prolonged bleeding time, and severely reduced platelet aggregation in response to the physiological agonists adenosine diphosphate (ADP), epinephrine, collagen, and ristocetin. Flow cytometric measurements showed that the contents of alphaIIb and beta3 were significantly decreased. Sequencing results demonstrated two different types of heterozygous mutations existed in the alphaIIb gene (c.2930delG and IVS15-1delG). The compound mutations were also confirmed in the patient's mother and father separately. CONCLUSIONS: The alphaIIbbeta3 deficiency of the proband was caused by two compound ITGA2B mutations, which were first reported in Chinese GT patients. The IVS15-1delG was first confirmed to cause an exon skipping.

[Effects of patient-controlled analgesia with small dose ketamine combined with morphine and the influence thereof on plasma beta-endorphin level in patients after radical operation for esophageal carcinoma].

OBJECTIVE: To evaluate the effects of patient-controlled analgesia (PCA) with small dose ketamine combined with morphine on analgesia and influence thereof on the plasma beta-endorphin (EP) level in the patients after radical operation for esophageal carcinoma. METHODS: Thirty ASAI-II patients, aged 35-65, weighing 42-75 kg, with visual analogue score>or=3, undergoing elective radical operation for esophageal carcinoma under general anesthesia received intravenous morphine 2 - 3 mg were randomly divided into 2 equal groups: group m receiving morphine 0.02 mg.kg(-1).h(-1), and with group mk receiving morphine 0.02 mg.kg(-1).h(-1) combined with ketamine 0.08 mg.kg(-1).h(-1) for 50 h. In the course of treatment the patients received intravenous injection of morphine 2-3 mg when the VAS was >or=3. VAS was recorded 4, 8, 20, 24, and 48 h after operation. The amount of morphine used after operation, PCA button pressing times (effective/active), side effects, and vital signs including pulse, saturation of blood oxygen, respiratory rate, heart rate, and average arterial pressure were recorded. Central venous blood samples were collected when entering the operation room (T0), by the end of operation (T1), and 6 h (T2), 24 h (T3), and 48 h (T4) after operation respectively to examine the beta-endorphin level. RESULTS: During the period 4-48 h after operation the VAS scores of the group mk were significantly lower than those of the group m in activity state (all P<0.05) and were not significantly different those of the group m at resting state (all P>0.05). The total amount of morphine consumed and the actual PCA button pressing times were significantly less in the group mk than in the group m (both P<0.05). The incidence rates of nausea, vomiting, and pruritus of the group mk were all significantly lower than those of the group m (all P<0.05). There were not significant differences in the incidence rates of dreaming and pseudoesthesia between these 2 groups. All the vital signs were stable in the 2 groups. The plasma beta-EP levels at the time point T1 of these 2 groups were both significantly higher than those at T0 (both P<0.05). The plasma beta-endorphin levels at T2-4 of the group mk decreased gradually from the level at T1 to the level at T0, and the plasma beta-endorphin levels of the group m rapidly decreased from the level at T0 to the T0 level and remained at this level to the 48 h after operation. CONCLUSION: The combination of small dose of ketamine with morphine provides optimal analgesia with low side-effect rate and little effect on the plasma beta-EP level.

[Dynamic change of plasma prethrombotic state molecular marker levels in perioperative period of patients and its clinical significance].

This study was aimed to investigate the dynamic changes of plasma prethrombotic state molecular marker levels during perioperation of patients and to provide laboratorial evidence for clinical diagnosis of these patients so as to take intervenient measure to high risk patients. 40 patients with gynecological and urological malignant tumors (without metastasis) and 20 patients with benign tumors and 20 healthy individuals were selected for analysis. The levels of plasm prethrombotic state molecular markers including TF, TFPI, TpP, PAI-1, P-S, TAT and D-D were measured by using ELISA method and transmission immunity nephelometry. The results showed that the levels of TF, TpP, D-D, P-S and TAT in plasma of patients with malignant tumors at 6 hours after operation were higher than that before operation, but the levels of TFPI and PAI-1 in these patients after operation were lower than before operation, and there was significant difference as compared with the levels of these markers before operation. At day 3 after operation, the levels of TF, TpP and D-D continuously increased; the level of PAI-1 begins to elevate, there were significant difference in comparison with that before operation; the levels of P-S and TAT decreased, but still were higher than that before operation. At day 7 after operation, the levels of TpP, TAT, P-S, TFPI and PAI-1 returned to levels before operation, but the levels of TF and D-D were still higher than that before operation, and showed significant difference from that before operation. In patients with benign tumors and non-operation patients, the levels of prethrombotic state molecular markers mentioned above at different points of time after operation did not present difference, except levels of TF and D-D that at 6 hours after operation were higher than that before operation. It is concluded that at 6 hours after operation of patients with gynecological and urological malignant tumours, the plasma levels of prethrombotic state molecular markers are in higher state of coagulation and fibrinolysis, at 3 days after operation these levels are mainly in coagulation state. At 7 days after operation, the level of these markers returned to levels before operation. At 6 hours after operation the levels of these markers in patients with benign tumors are in mild coagulation state.

Effects of different drainage procedures on levels of serum endotoxin and tumor necrosis factor in patients with malignant obstructive jaundice.

OBJECTIVE: To assess the influence of different drainage procedures on the levels of serum endotoxin and tumor necrosis factor (TNF) in patients with malignant obstructive jaundice (MOJ). METHODS: The levels of endotoxin and TNF in 46 patients with MOJ were measured before and after cholangiojejunostomy (CJ) or external bile drainage (EBD). RESULTS: In the CJ group, the levels of postoperative serum endotoxin and TNF 10 days after operation were significantly lower than those before operation (P<0.01). In the EBD group, no significant changes were observed in endotoxin and TNF levels before and after operation (P>0.05). No significant differences were seen between the two groups before operation (P>0.05), but the levels of endotoxin and TNF in the CJ group were significantly lower than those in the EBD group after operation (P<0.01). CONCLUSIONS: Cholangiojejunostomy other than external bile drainage can decrease the levels of serum endotoxin and TNF effectively, although both of them are able to release jaundice. Cholangiojejunostomy should be performed as soon as possible for patients with unresectable malignant tumor.