Volume 111  ·   Issue 12  ·  1998

OBJECTIVE To establish a convenient method to detect the genomic population with hepatitis C virus (HCV) at nonstructure 5A (NS5A) region and to determine the correlation between the genomic population complexity at NS5A region and disease stage. METHODS The sera from 52 patients with chronic hepatitis C virus infections were analysed using single strand conformation polymorphism (SSCP). In the SSCP, an asymmetric polymerase chain reaction (PCR) was carried out on the 455 bp products of the first round PCR at the NS5A region and the number of band of single strand deoxyribonucleic acid (DNA) which reacted with complemental DNA probe specific for the NS5A region after gel electrophoresis was analyzed. RESULTS In 90% patients with chronic persistent hepatitis, the bands of single strand DNA was limited to one, and in those with chronic active hepatitis or liver cirrhosis, two or more bands of DNA were frequently detected. In about half of patients with hepatocellular-carcinoma, three or more bands were found. The number of bands increased with the progression of liver disease. The multivariate analysis showed that the progression of liver disease was the independent factor of viral diversity (P<0.025) and was not related to the age, sex, the route of infection and the titer of hepatitis C virus ribonucleic acid (HCV RNA). CONCLUSIONS These results suggest that the genomic variability of HCV at NS5A region increases with the progression of liver disease, and this may be closely related to the clinical features of type C liver disease.

OBJECTIVE To examine whether tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) genes can be cotransduced into the same target striatal cells using adeno-associated virus (AAV) vectors, and to determine whether the cotransduction would result in better biochemical change than the TH gene alone. METHODS TH and AADC genes were cotransduced into cultured striatal cells with separate AAV vectors. Expressions of TH and AADC were detected by immunocytochemistry; intracellular catecholamine levels were assayed by high-performance liquid chromatography (HPLC). RESULTS TH and AADC genes were efficiently cotransduced into the striatal cells. Specifically, the coexpression of TH and AADC resulted in more effective dopamine production compared with the TH gene alone. CONCLUSIONS Using AAV vectors, coexpression of TH and AADC in the striatal cells might be a useful approach to gene therapy for Parkinson's disease.

OBJECTIVE To study the pharmacokinetics and metabolism of arsenic trioixide (As2O3) and its main side effects. METHODS As2O3 was administered intravenously at the dose of 10 mg per day for the treatment of 8 relapsed acute promyelocytic leukemia (APL) patients. The arsenic content was measured by Gas-phase chromatography. RESULTS The plasma maximal concentration (Cpmax) was 0.94±0.37 mg/L (x±s), time to peak concentration (Tp) was 4 hours, plasma distribution half-time (t1/2α) and elimination half-time (t1/2β) were 0.89±0.29 hours and 12.13±3.31 hours, respectively. Apparent distribution volume (Vc) was 3.83±0.45 L, system clearance (CLs) was 1.43±0.17 L/h, and area under curve (AUC) was 7.25±0.97 mg.h/L. The continuous administration of As2O3 did not alter its pharmacokinetic behaviors. During As2O3 treatment, 24-hour arsenic content in urine accounted for 1%-8% of the daily dose (10 mg). When arsenic accumulation in hair and nail increased continuously, the peak concentration could be five to seven-fold higher than that of pre-treatment. Importantly, arsenic contents in both urine and hair or nail declined gradually after drug withdrawal. No bone marrow suppression or severe organ-impairment was found. CONCLUSIONS As2O3 is a relatively safe and effective remedy in the treatment of patients with relapsed APL, in spite of certain degree of arsenic accumulation in some tissues.

OBJECTIVE To investigate the effects of wild-type p53 (wtp53) on inducing apoptosis by restoring wtp53 expression in pancreatic adenocarcinoma cell line (PC-2) which contains mutant p53, and the interaction between murine double minute-2 (MDM2) and wtp53 in pancreatic adenocarcinoma. METHODS A recombinant retroviral vector expressing wild-type p53 was constructed and packaged by packaging cell line PA317 cells using calcium phosphate coprecipitation method. The supernatant of the packaged cells PA317 was used to transfect the pancreatic carcinoma cell line (PC-2), then a transformed cell line PC-2/swtp53 was established. The recombinant vector pCMV-MDM2 was transduced into PC-2/swtp53 cell line by lipofectin-mediated method, a double transfected cell line (PC-2/swtp53/pCMV-MDM2) was formed. To determine the integration and expression of exogenous wtp53 gene in the transfected cells, polymerase chain reaction (PCR), Western blot and immunoprecipitation analyses were performed. Apoptosis was analyzed by means of flow cytometry, in situ terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) analysis and DNA agarose gel electrophoresis. RESULTS Transduction with the retroviral vector resulted in integration and expression of wtp53 gene in host cells. The apoptotic cells in PC-2/swtp53 and PC-2/swtp53/pCMV-neo cell lines were 12.1%-12.9%, while the double transfected cell line, PC-2/swtp53/pCMV-MDM2, showed less (3.2%) apoptotic cells than its parent cell lines. CONCLUSIONS Restoration of expression of wild-type p53 with a retroviral vector can increase programmed cell death of pancreatic adenocarcinoma cells (PC-2) containing mutant p53. The overexpression of MDM2 protein has a negative regulating role in wtp53-induced apoptosis in PC-2 cell.

OBJECTIVE To analyse the risk factors of heterotopic ossification after spinal cord injury. METHODS Of 104 patients with spinal cord injury, 47 (45.2%) were complicated by heterotopic ossification of the hip. These patients with heterotopic ossification were compared with 57 patients without heterotopic ossification. RESULTS Statistical analysis showed that complete paraplegia, spasticity and pressure sore were significantly (P<0.05) or highly significantly (P<0.01) related to heterotopic ossification formation. The coexistence of two or three of these factors in the paraplegic patients was found to significantly (P<0.01) enhance the risk of heterotopic ossification formation. CONCLUSIONS When the spinal cord injured patients have single or multiple risk factors, they should be predicted for susceptibility of heterotopic ossification.

OBJECTIVE To investigate the effect of horizontal platform supported (HPS) prosthesis on cementless total hip replacement for surgical treatment of arthritis in a long-term follow-up study. METHODS Clinical and radiographic follow-up of 65 consecutive primary cementless porous coated HPS total hip replacements, which were implanted in 60 patients between 1982 and 1989, was carried out. RESULTS The 53 hips in 50 patients were evaluated both clinically and radiographically. The average follow-up was 6.8 years (range: 5 to 12 years). According to the Harris hip score, 52 (98%) of the hips had sustained an excellent or good result with an average score of 92. At the time of final assessment, no patient experienced anterior thigh pain. There were two revisions performed early in the series due to technical failures. Radiographically, osteolysis and bone remodelling were assessed. CONCLUSIONS The findings suggest that the clinical and radiographic results after cementless total hip replacement for primary hip arthroplasty may be favourably influenced by the use of the proximal stress loaded HPS femoral component.

OBJECTIVE To investigate the correlation between angiogenesis and tumor growth pattern as well as the lymph node metastasis to reveal the significance of vascularity in the early stage of gastric cancer. METHODS 97 specimens from patients with early gastric cancer were studied by immunohistochemical method using anti-factor Ⅷ related antigen antibody. RESULTS Microvessel count was related to tumor growth pattern. The mean vessel count was higher in superficially spreading and penetrating types of tumors. Lymph node metastasis was correlated to microvessel count. Tumors with lymph node metastasis had higher microvessel counts than those without lymph node metastasis. CONCLUSIONS In the early stage of gastric carcinoma, angiogenesis is correlated with tumor growth pattern and lymph node metastasis. Identification of tumors with high density of vascularization is beneficial for closer follow-up and adjuvant therapy.

OBJECTIVE To study the effect of pericardial devascularization combined with Latarjet's innervation on portal hypertension. METHODS Forty-eight patients undergoing pericardial devascularization combined with Latarjet's innervation were compared with 57 patients with devascularization. Clinical results were evaluated by postoperative portal vein pressure, postoperative rebleeding, operative mortality, abdominal distension, sudden diarrhea, and gastric retention. RESULTS The incidence of rebleeding, mortality, abdominal distension, sudden diarrhea, and gastric retention was 2%, 6.3%, 6.3%, 4.2% and 0% respectively in pericardial devascularization combined with Latarjet's innervation, and 12.5%, 12.3%, 24.6%, 15.6% and 14% respectively in devascularization. CONCLUSIONS Pericardial devascularization combined with Latarjet's innervation preserves the normal function of gastric emptying. This method plays an important role in maintaining nutritional supply and digestive function.

OBJECTIVE To assess retrospectively the clinical value of androgen receptor (AR) levels in primary hepatocellular carcinoma (HCC) as a prognostic factor of the disease. METHODS Fresh HCC tissue and the surrounding liver tissue were obtained surgically from 32 patients with HCC, and preserved in liquid nitrogen. The levels of AR in all specimens were determined by radio-ligand binding assay. RESULTS The median level of AR was 42.8 fmol/mg protein in the cancerous tissue and 48.3 fmol/mg protein in the surrounding non-cancerous liver tissue. The overall survival rate of the patients with AR<30 fmol/mg protein in either HCC or the non-cancerous liver was significantly higher than that of the patients with AR ≥ 30 fmol/mg protein (P<0.05 and P<0.01, respectively). The relative risk on prognosis was 3.27 (P<0.01) for AR level in HCC and 6.06 (P<0.001) for AR level in the non-cancerous tissue. The main prognostic factors except the tumor size were not different between the group with higher AR level and that with lower AR level in HCC. The AR level in HCC had a positive correlation with the tumor size (r = 0.44, P<0.05). CONCLUSIONS AR can be detected in HCC and the AR status might be a prognostic parameter that provides additional predictive information on the survival. Different AR status might define a real difference of biological characteristics between HCCs.

OBJECTIVE To determine the effect of PGE1 on liver microcirculation disturbance following orthotopic liver transplantation in rats. METHODS Forty male adult Wistar rats were divided randomly into 3 groups. Eight transplantations were established in both the experimental and control group, while in the sham group, the liver was dissected like in the experimental group, but no resection was performed. In the experimental group, PGE1(0.5 μg/kg·min-1) was injected intravenously into the donor before the operation, and added (1 mg/L) to the flush and preservation fluid, while PGE1 was replaced by normal saline in the control group. Confocal laser scan microscopy, biochemical test, and optical and electronic microscopy were used. RESULTS In the control group the reperfusion state was poor, leukocyte infiltration appeared in the center of lobule, and transaminase rose after transplantation. In the experimental group distinctive improvement was seen as compared with the control group (P<0.05). Histological findings showed progressive degeneration and necrosis following transplantation in the control group, while in the experimental group the histological changes were improved to some degree by the use of PGE1. CONCLUSIONS In liver transplantation, ischemic reperfusion damage may lead to hepatic microcirculation disturbance, which is the major cause of graft failure. Infusing PGE1 into the donor intravenously before ischemia and adding PGE1 to the cold storage fluid could improve hepatic microcirculation, and thus reducing ischemic reperfusion damage in liver transplantation.

This issue of Chinese Medical Journal (CMJ) focuses on many aspects of hepato-biliary-pancreatic surgery, which represent some of lated development of general surgery in China.

Torsion of the greater omentum is a rare condition of acute abdomen. About 300 cases were reported after the first description by Eitel in 1899. Primary omental torsion may occur in any age and only 15% in children. In this article, an additional case of primary omental torsion with necrosis was presented.

Rathke's cleft cysts (RCC) are usually incidental autopsy findings and are asymptomatic. Although symptomatic RCC is extremely rare, recent advances in magnetic resonance imaging (MRI) provide the means by which to detect them preoperatively. RCC may become symptomatic when its size increases and it compresses the surrounding tissues: the hypothalamus, hypophysis, optic nerve and chiasma.

The use of single lead for atrial synchronous ventricular (VDD) pacing in patients with high grade atrioventricular (AV) block and normal sinus node function is an acceptable alternative to dual chamber (DDD) pacing. Implantation and follow up procedures are simplified, and cost is usually reduced by more than the cost of an additional atrial lead. With the use of either diagonally arranged dipole or closely spaced ring electrodes, reliable atrial sensing can be achieved using differential atrial amplifier and high atrial sensitivity. Also oversensing is infrequently observed using provocation tests and dynamic recordings, clinical undersensing is unusual and minimized by programming to the highest atrial sensitivity. However, as atrial pacing is not possible, loss of AV synchrony and rate response may occur for unrecognized or progressive sinus node disease and lower rate limit. The development of single lead dual chamber pacing system may overcome this limitation. Recent studies have demonstrated that atrial pacing can be effective either with the use of a special pacing lead configuration or via floating atrial electrode with a novel stimulation method. Overlapping biphasic impulse (OLBI) can reduce atrial pacing threshold. Early clinical experience suggested that this new pacing method can provide effective and reliable atrial pacing with a relatively low incidence of diaphragmatic pacing. Thus the problem of atrial sensing is solved with a single pass lead but further long term evaluation is required to assess the efficacy and feasibility of new instrumentation for single lead dual chamber pacing.