Volume 113 · Issue 12 · 2000

Objective To elucidate the association of plasma factor VI coagulant activity(FⅦc)with the risk of myocardial Infarction(Ml)and to assess the influence of factor Ⅶ gene Mspl polymorphism and lipid metabolism on FⅦc in the Chinese. Methods A total of 137 patients with angiographically confirmed Ml and 125 healthy individuals were evaluated retrospectively. Plasma FⅦc was measured by one-stage prothrombin time, and FⅦ genotype was determined after Mspl digestion of polymerase chain reaction-amplified genomic DNA. Serum lipid levels were assessed by routine methods. Results MI patients had significantly higher levels of FⅦc(119.5% ± 22.7% vs 99.9% ± 21.8%, P<0.01)and total serum cholesterol(5.80 ± 1.06 mmol/L vs 5.53 ± 1.08 mmol/L, P < 0.05)than controls, but only FⅦc independently correlated with the risk of Ml(OR = 1.04, P<0.01). There were no significant differences in FⅦ genotype or allele frequency between patients and controls(P >0.05). Subjects with the Gln353 allele were associated with significantly lower FⅦc levels than Arg353 hornozygotes(99.7% ±19.3% vs 111.4% ±24.6%, P<0.05). Serum triglyceride was positively correlated with plasma FⅦc in both control(r = 0.25, P<0.01)and case (r = 0.87. P < 0.01)groups, but this correlation was restricted to Arg/Arg genotype (r = 0.68, P < 0.01). A significant correlation of total serum cholesterol with FⅦc only appeared in Arg/Arg homozygotes(r = 0.17, P <0.01). Conclusions Our findings support the role of plasma FVIc as a risk factor for Ml in Chinese. Plasma triglyceride and FⅦ gene Mspl polymorphism are two independent determinants of FⅦc. Assay of this polyrnorphism will be helpful in determining who will benefit most from lipid-lowing therapy. Chin Med J 2000; 113(12): 1059-1063

Objectives To investigate the effect of advanced glycosylation end products(AGEs)on the activity of protein kinase C(PKC)in human peripheral blood mononuclear cells(PBMC)and to observe whether aminoguanidine(AG)can influence the effect of AGEs. Methods After P8MC were isolated from hurnan peripheral blood and incubated with different concentrations of AGEs-BSA for various periods, total PKC activity in PBMC was determined by measuring the incorporation of 32P from [γ-32 P] ATP into a special subtstrate using Promega PKC assay kit. Results AGEs-BSA increased the total PKC activity in PBMC from 83.43± 6.57 pmol/min/mg protein to 116.8±13.82 pmol/min/mg protein with a peak at 15 min. AGEs-BSA also increased the total PKC activity in a concentration-dependent manner from 83.1 ± 6.4 pmol/min/mg protein(control)to 119.1 ± 13.3 pmol/ min/mg protein(control vs AGEs-BSA 400mg/L, P < 0.01). Furthermore, AGEs-BSA induced an elevation of PKC activity in a glycosylating time-related manner, from 80.9 ± 8.2(control)to 118.3 ± 11.5 pmol/min/mg protein(glycosylation for 12 wk, P <0.01). The total PKC activity stimulated by AGEs-BSA pretreated with AG (100, 200 mg/L)was markedly lower than that of AGEs-BSA group not pretreated with AG(P< 0.05, P<0.01). Conclusions AGEs-BSA increased the total PKC activity in PBMC in a concentration and incubation time dependent manner. The ability of AGEs-BSA to stimulate PKC activity was markedly decreased by pretreatment of AGEs-BSA with AG. Chin Med J 2000; I13(12): 1068-1070

Objective To study the relationship between the burden of Pneurnocystis carinii(P. carinii) and the inflarnmatory reaction and biochemical markers in bronchoalveolar lavage fluids(BALF)in a rat model of P, carinii pneumonia(PCP). Methods Clean grade 50 male Sprague-Dawiey rats were immunosuppressed by a subcutaneous injection of 25mg cortisone acetate twice a week for 8-12 weeks; the PCP model was successfully induced in 14 rats. The inflammatory reaction and biochemical markers of the activity of lactate dehydrogenase(LDH), alkaline phosphatase(ALP)and type N collagenase(matrix metalloproteinases, MMP-2, MMP-9)as well as the values of total protein(TP)and albumin(ALB)in BALF between the mild burden group of P. carinii(involved alveoli <25% per 100 alveoli, Group A)and the moderate to severe burden group(involved alveoli ≥ 25% per 100 alveoli, Group B)were measured. The other six clean grade SD rats served as normal control group(Group C). Results The total white cell count in BALF was higher in Group B [(6.8 ± 1.7)× 106/L] than in Group A -(3.8 ± 1.2)× 106/L](P < 0.01); however, there were no differences in white cell differentiation. Assays of biochemical markers showed that ALB in BALF in Group B(0.893 ± 0.469 g/L)was Increased in comparison with Group A(0.262 ± 0.169 g/L〉; it was only 0.026 ±0.021 g/L in Group C. The contents of TP and activities of LDH were higher in Group B(TP 1.756± 0.706 g/L, LDH 2580 ± 550 U/L)than in Group A(TP 0.784 ± 0,553 g/L, LDH 1410 ± 620 U/L); the values of TP and LDH were 0.063 ± 0.020 g/L and 370 ± 250 U/L respectively in Group C. The activity of Type IV collagenase, including MMP-2 and MMP-9, was higher in Group B than in Group A(P< 0.01)(MMP-2: 1102 ± 169 grey value vs 459 ± 274 grey value; MMP-9: 1218: ± 257 grey value vs 449 ±225 grey value). There was no activity of Type IV collagenase in BALF of Group C. No statistically significant difference was observed in ALP between the groups B and A. Conclusions These results indicate that there is a significant correlation between the burden of P. carinii in lung tissues and the inflarmnatory reaction as well as biochemical markers of the resultant activity of lung injury. Chin Med J 2000; 113(12): 1071-1074

Objective To understand the clinical significance of sequence variations in the hypervariable region(HVR)of hepatitis C virus during infection. Methods Eight patients with acute hepatitis C and 20 patients with chronic hepatitis C were followed up for two years. Blood samples were taken at intervals of six months for analysis of HCV-HVR sequences by reverse transcription-polymerase chain reaction(RT-PCR)and direct sequencing methods . Results HCV-HVR sequences of the 28 patients changed in various degrees. 92% of these nucleotide substitutions led to changes of corresponding amino-acid sequences. Only 8% of changed nucleotide were synonymous substitutions. Of 27 amino acids variation of amino acid ranged from 1 to 20(mean 8, 30%). The most common nucleotide substitution(62%)occurred in the first position of codon, 31% in the second and the rest in the third. HVR variation rate was 0.89 × 10-1 per genome site per year in acute hepatitis C, compared with 2.31 × 10-1 per genome site per year in chronic hepatitis C(P<0.05). but had no relation to HCV subtype. Variation of HVR in the flare up type(ALT> 150 μ/L) was much more than that in the quiescent type(ALT < 100 μ/L). Conclusion Our results suggested that sequence variation of HVR during HCV chronic infection seems to be an adaptive response to HCV to evade the host imrnune pressure and might play a major role in the establishment of persistent infection as well as in the flare-up of hepatitis. Chin Med J 2000; 113(12): 1075-1079

Objective To study whether liver cirrhosis associated with Helicobacter pylori(H. pylori)infection will induce increased serum ammonia and whether the peripheral serum ammonia reflects the level of portal vein serum ammonia. Methods Blood was taken from the portal vein and the cubital vein in cirrhotic patients with and without H. pylori infection and non-cirrhotic patients(splenic rupture)with and without H. pylon infection, and the serum ammonia was measured. Results The mean levels of serum ammonia in the group of cirrhotic patients with H. pylori rnfection were 167.82 ± 8.97 μmol/L(portal vein)and 142.2 ± 13.35 μmol/L(cubital vein). They were increased significantly as compared with cirrtiotic patients without H. pylori infection(47.68 ± 12.03 μmol/L portal vein and 37.23 ± 7.04 μmol/L cubital vein), and also compared with the groups of splenic rupture patients with and without H. pylori infection(P<0.01). There was no significant difference between the serum ammonia level of the cubital vein and portal vein(P> 0.06). Conclusions H. pylori infection can induce an increase in serum ammonia in patients with liver dysfunction, and the peripheral serum ammonia measurement may replace the portal vein serum ammonia as a monitoring method. Eradication of H. pylori in cirrhotic patients may prevent hepatic encephalopathy(HE). Chin Med J 2000; I13(12): 1080-1081

Objective To evaluate apoptosis in lupus nephritis and the relationship between the existence of apoptotic cells in renal tissue and histopathological or clinical changes. Methods Apoptosis was detected by in situ nick-end labeling techniques(TUNEL)in renal biopsies from 25 patients with type IV lupus nephritis(LN), 12 patients with lgA nephropathy IgAN, 4 patients with idiopathic mesangioproliferative glomerulonephritis(MsPGN)and 3 patients with acute poststreptococcal glornerulonephritis(APGN). Normal renal tissue obtained at nephrectomy for hypernephroma in 4 adults was used as control. Proliferating cells were identified by proliferating cell nuclear antigen(PCNA) in these patients. Results Compared to other proliferative glomerulonephritis and controls, the patients with lupus nephritis had less apoptotic cells, a higher ratio of PCNA + cells/TdT+ cells(P/T)in renal tissues; and their P/T ratio in glomeruli and tubulointerstitium correlated with the chronicity index, r = 0.4983(P=O.0132), r =0.8399(P < O.OO1), r=O.6614(P=0.0033). respectively. P/T ratios in the glomerulus and tubule had a positive correlation with 24-hour urinary protein, r = 0.8554(P < 0.001)and r = 0.7134(P = 0.001); and a negative correlation with creatinine clearance(Ccr), r=-0.4880(P = 0.0133)and r =-0.7229(P=0.001), which in tubules positively correlated with serum creatinine(Scr), r = 0.4107 (P =0.0414). Conclusions Apoptosis is reduced in proliferative lupus nephritis. intense proliferation without a commensurate increase in apoptosis is a possible mechanism that Jeads to chronic progressive renal histopathological changes. Chin Med J 2000; 113(12): 1082-1086

Objective To study the relationship between advanced glycosylation end products(AGE) and protein kinase C(PKC), and their effects on renal alteration in diabetic rats. Methods Insulin or aminoguanidine was administered to diabetic rats. Blood glucose, hemoglobin A1c(HbA1c). glomerular tissue extracts AGE(GTE-AGE), PKC, glomerular basement membrane thickness(GBMT)and urine protein/creatinine(Pr/Cr)ratio in diabetic rats were measured and analysed. Results Levels of blood glucose. HbA1c and AGE, PKC activity, the Pr/Cr ratio and GBMT were all significantly increased(P values all less than 0.01)in diabetic rats. Insulin could decrease the formation of HbA1c and AGE, and improve PKC activity. Aminoguanidine had no influence on PKC activity(P>0.05)although it decreased the formation of AGE. Both drugs could delay the increase of urine Pr/Cr ratio and GBMT(P<0.05 or P<0.01). Conclusions Chronic hyperglycemia may lead to an increase of PKC activity. HbAlc and AGE may not directly contribute to alterations of PKC activity, but the increase of PKC activity could promote the action of AGE on GBM thickening. It is important to inhibit the formation of AGE and reduce the PKC activity so as to prevent or delay the development of diabetic nephropathy. Chin Med J 2000; 113(12): 1087-1091

Objective To clarify the dependence of neural nitric oxide synthase mRNA(nNOSmRNA)and endothelial nitric oxide synthase mRNA(eNOSmRNA)on androgens(testosterone [T] and dihydrotestosterone [DHT]). Methods 160 mate Sprague Dawley(SD)rats were divided into Groups A(56 rats, 5 weeks old), B(50 rats, 10 weeks old)and C (54 rats, 58 weeks old). Groups A, B and C were all subdivided respectively into five Subgroups. Subgroup 1: intact controls; Subgroup 2: castrated; Subgroup 3: castrated with testosterone undecanoate 25 mg/kg· mon-1, intramuscular injection. Subgroup 4: castrated with testosterone undecanoate 50 mg/kg · mon -1, intramuscular injection and Subgroup 5: treated with finasteride 4.5 mg/kg · day1, orally, Four and ten weeks after treatments described above, one half of the rats were killed. Serum samples were taken for measurements of T. free testosterone(FT)and DHT by radioimmunoassay. Penile samples were treated with liquid nitrogen and then stored at-80℃. nNOSmRNA and eNOSmRNA were detected by semiquantitative reverse-transcription polymerase chain reaction(RT-PCR)and Dot blot. Results There was no significant difference between Subgroup 1 and Subgroup 2 or Subgroup 5 in all Groups A, B and C. The expression of penile eNOSmRNA of Group A was significantly increased(4 weeks model)(P < 0.05)or increased(10 weeks model)(P> 0.05)in Subgroup 2 or 5 compared with those in Subgroup 1. There was no significant difference between Subgroup 1 and Subgroup 2 or Subgroup 5 of Group B in 4 weeks model(P> 0.05)•There was an elevation when animals were castrated or treated with finasteride in the 10 weeks model. The expression of penile eNOSmRNA of Group C was significantly increased(10 weeks model)(P < 0.05)or increased(4 weeks model)in Subgroup 2 compared with those in Subgroup 1. The production of eNOSmRNA in Subgroup 5 was also increased(including 4-and 10-week models). When T was supplied for castration, the penile eNOSmRNA was decreased to some extent; the greater the dose of T given, the lower penile eNOSmRNA was observed. Conclusions The expression of eNOSmRNA in SD rat penile tissue increases while T or DHT diminishes. Sometimes androgens modulate penile eNOSmRNA in opposite directions. There is no correlation between the expression of nNOSmRNA and androgens(including T and DHT). Androgens give rise to penile erection probably not via the NOS pathway. Chin Med J 2000; 113(12): 1092-1095

Background The incidence of breast cancer in Hong Kong is increasing and breast self-examination(BSE)as a screening tool is becoming more popular. especially among first-degree relatives(FDR)of breast cancer victims. BSE may be more applicable to Chinese women as their breast size is smaller. This study explores the BSE practice in this group of women. Methods A cross sectional study was conducted by sending questionnaires to 330 FDR of breast cancer patients treated in the Department of Surgery, University of Hong Kong. BSE behavior was studied with respect to its frequency, awareness, completeness and confidence of practice、 Results 110 subjects returned the questionnaires with a response rate of 33%, The mean age of the respondent was 37 years. Only 57 women(52%)were practicers. The practicers have a stronger BSE awareness(P < 0.01)and a lower mean score on thought barriers(P = 0.002)than the non-practicers. 40% of the practicers gain their BSE knowledge through clinicians and their mean period of practice was 3.2 years. 68% of the practicers performed BSE completely. The overall confidence rate was 35%, but the rate was 43% among those who performed complete BSE. Thirteen factors possibly related to the completeness and rate of confidence of BSE examination were studied. The only factor that significarrtly detemined completeness was the time spent for each examination(P = 0.002). The complete practicers required a longer time than the incomplete practicers(6.60 and 2.96 min, respectively). Women with a stronger BSE intention(P = 0.001)and a lower mean score on thought barriers(P = 0.001)performed the examination confidently. Conclusions Slightly over half of the FDR practice BSE. The majority perform a complete BSE but they are not confident in finding abnormalities. Women spending more time on BSE are associated with a higher rate of completeness. However, only those with a stronger BSE intention and lesser thought barriers are more confident in their practice, Chin Med J 2000; 113(12): 1100-1103

Objectives To report the clinical experiences of simultaneous hepatorenal transplantation. Methods We performed simultaneous hepatorenal transplantation in one patient with liver cinrtiosis of hepatitis B and uremia of chronic nephritis on February 1, 1999 and one patient with liver cirrhosis of hepatitis B complicated by hepatorenal syndrome on March 12, 1999. The donors were heart arrest cases. Rapid muttiple organ harvesting techniques and UW solution infusion in situ were used. Liver and kidney transplantation were orthotopic and ordinary methods, respectively. Immunosuppressive drugs consisted of cyclosporine, Cellcept, ALG and cortstco steroids. Lamividine was used on day 50 and day 40 postoperation, respectively. Results Both transplanted organs rapidly achieved normal function postoperation and the patients recovered well but suffered mild kidney rejection day 110 postoperation in No 1 patient. In No 2 patient, acute renal function failure, mental symptoms, muscle spasm, cerebral artery thrombosis, inhalation pneurnonia and chronic liver graft rejection ensured sequentialty but were controlled. The patients have survived for more than nine and eight months, respectively, with normal life quality. Conclusions Combined hepatorenal transplant is a radical treatment method for liver and kidney function failure and requires more comprehensive techniques than isolated single organ transplantation. Preventing the recurrence of hepatitis B by oral iamividine may be a key to long-term survival. Chin Med J 2000; J 13(12): 1104-1107