OBJECTIVES--This study examines the acute effects of two differing beta adrenergic blocking agents (metoprolol and a third generation vasodilating beta blocker) on plasma concentrations of atrial ...natriuretic factor (ANF), brain (ventricular) natriuretic factor (BNF), and haemodynamic variables in patients with heart failure. SETTING--University teaching hospital. METHODS--20 patients with impaired left ventricular systolic function ejection fraction 32 (SEM 2.3)% were randomised in a double blind manner to receive either oral metoprolol 6.25 mg twice daily or celiprolol 25 mg daily. Haemodynamic variables were evaluated by Swan-Ganz pulmonary artery catheter over 24 hours. ANF and BNF concentrations were measured at baseline, 5 h, and 24 h by radioimmunoassay. RESULTS--At baseline ANF and BNF concentrations were considerably raised compared to the normal range. Treatment with metoprolol caused ANF to rise further to 147% of the basal level at 5 h (P = 0.017) and 112% at 24 h (P = 0.029). This was associated with a small but non-significant rise in pulmonary capillary wedge pressure. Cardiac output and systemic vascular resistance were unchanged at 24 h. In contrast, after celiprolol ANF fell to 90% of basal levels at 5 h and to 74% of basal level at 24 h (P = 0.019), associated with a small but non-significant fall in pulmonary capillary wedge pressure -3.3 (2.7) mm Hg and systemic vascular resistance, and rise in cardiac output from 3.2 (0.2) to 4.0 (0.4) l/min (P = 0.04). BNF concentrations rose to 112% of baseline at 5 h (P = 0.09) after metoprolol but fell slightly, to 91% of baseline values, after celiprolol (NS). CONCLUSIONS--Metoprolol, even in very low doses (6.25 mg), produced a rise in ANF and BNF, although minimal haemodynamic changes were detected. In contrast, a vasodilating beta blocker was associated with a significant fall in ANF and BNF and a small rise in cardiac output. This study confirms both the advantages of vasodilating beta blockers over metoprolol for initial treatment of heart failure and the usefulness of ANF and BNF measurements for the assessment of drug effects in heart failure compared to traditional haemodynamic measurements.
Using 21 microsatellite polymorphic markers spanning both p and q arms, we have performed detailed deletion mapping on chromosome 9 in 18 primary nasopharyngeal carcinomas. All 18 tumors were ...informative at multiple loci. Eleven of the 18 cases (61%) demonstrated allelic deletion of chromosome 9. Among these 11, 6 cases are likely to be tumors with monosomy of chromosome 9. The other 5 cases demonstrated partial deletion by showing multiple areas of allelic loss. In one of the 5 cases, a homozygous deletion region was identified which includes D9S126, D9S171, and IFNA loci at 9p21-22, situated between loci D9S161 (9p21) and D9S162 (9p21-22). The presence of a homozygous deletion strongly suggests the presence of tumor suppressor gene(s) involved in the tumorigenesis of nasopharyngeal carcinoma. The same region has been reported to include some potential tumor suppressor gene loci in other cancers. This is the first reported finding of frequent genetic loss observed on chromosome 9 in nasopharyngeal carcinomas in addition to allelic loss on chromosome 3p at specific regions. Our results suggest that tumorigenesis and progression of nasopharyngeal carcinomas, like other solid tumors, involves multiple genetic changes associated with the inactivation of tumor suppressor genes.
Normal nasopharyngeal mucosa contains varying amounts of lymphoid tissue, which in adults may be minimal or absent. Nasopharyngeal mucosa with minimal lymphoid tissue has a regular follicular pattern ...on narrow-band imaging; pale follicles have thin, dark borders and the ratio of the pale follicle to the dark border (pale-to-dark ratio) is roughly 90%. In some patients undergoing routine nasopharyngeal endoscopy, the pale-to-dark ratio is reversed on narrow-band imaging, with dark centres surrounded by pale borders and a pale-to-dark ratio of roughly 50%. These dark follicles may represent abnormal capillary loops, as they have the same appearance as microvascular changes seen on narrow-band imaging of the oesophageal mucosa which indicate dysplasia or malignancy. While this observed change in the follicular pattern may be an early event in the evolution of nasopharyngeal carcinoma, the significance of this finding remains to be confirmed by a larger-scale study.
BACKGROUND: We previously conducted a prospective study to show that nasopharyngeal cancer (NPC) screening with circulating Epstein–Barr virus (EBV) DNA analysis can improve survival. However, the ...long-term significance of positive results in individuals without cancer was unclear. METHODS: We conducted a second-round screening at a median of 43 months after the initial screening. Participants with detectable plasma EBV DNA were retested in 4 weeks, and those with persistently positive results were investigated with nasal endoscopy and magnetic resonance imaging. RESULTS: Of the 20,174 volunteers who participated in the first-round screening, 17,838 (88.6%) were rescreened. Among them, 423 (2.37%) had persistently detectable plasma EBV DNA. Twenty-four patients were identified as having NPC. A significantly higher proportion of patients had stage I/II cancer than in a historical cohort (67% vs. 20%; chi-square test, P<0.001), and they had superior 3-year progression-free survival (100% vs. 78.8%). Compared with participants with undetectable plasma EBV DNA in the first round of screening, participants with transiently and persistently positive results in the first round were more likely to have a cancer identified in the second round, with relative risks of 4.4 (95% confidence interval, 1.3 to 15.0) and 16.8 (95% confidence interval, 5.7 to 49.6), respectively. CONCLUSIONS: Individuals with detectable plasma EBV DNA but without an immediately identifiable NPC were more likely to have the cancer identified in another round of screening performed 3 to 5 years later. (Funded by Kadoorie Charitable Foundation and others; ClinicalTrials.gov number, NCT02063399.)
The traditional Chinese herbal formula Cang Er Zi San has been used for the treatment of rhinitis, paranasal sinusitis, and allergic rhinitis for several centuries. However, its therapeutic ...mechanisms remain largely unclear.
To study the effects of Shi-Bi-Lin (SBL), a modified Cang Er Zi San formula, on cytokine release from and expressions in the human mast cell line (HMC-1).
The HMC-1 was preincubated with different concentrations of SBL extract solution 1 hour before being stimulated with 25 ng/mL of phorbol myristate acetate plus 2.5 x 10(-7)M calcium ionophore A23187 and then further incubated for 6, 12, and 24 hours, respectively. The cell culture supernatants were harvested, and the cytokines of interleukin 4 (IL-4), IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) in the supernatants were measured by enzyme-linked immunosorbent assay. Furthermore, the total RNA of the cells was extracted, and the cytokines' messenger RNA expressions were examined using semiquantitative reverse transcriptase-polymerase chain reaction.
After different incubation periods at different concentrations, SBL could potently inhibit the cytokines of IL-4 and TNF-alpha and modestly affect IL-6 but not obviously affect IL-8 release from the HMC-1. However, no inhibitory effects were detected on the messenger RNA expressions of these cytokines.
These results demonstrate that SBL could modulate the mast cell-mediated hypersensitivity reaction in allergy. Inhibition of mast cell-derived IL-4 and TNF-alpha might explain the efficacy of SBL in treating allergic disease.
To identify factors related with successful pregnancy in renal transplant recipients and the effect of pregnancy on long-term graft outcome.
The study group consisted of 48 women who conceived after ...undergoing renal transplantation (total pregnancies 74). The control group consisted of 187 nonpregnant female renal transplant recipients.
Mean ages at the time of transplantation and pregnancy were 28.0+/-4.0 years and 31.6+/-4.1 years, respectively. The mean interval from transplantation to pregnancy was 40.2+/-27.1 months. Outcomes included 49 live births, 12 terminations, 9 miscarriages, 3 stillbirths, and 1 ectopic pregnancy. Eleven of the 74 pregnancies (15%) were within 1 year of transplantation, resulting in seven live births, two miscarriages, and two terminations. Live births were associated with younger age at the time of transplantation (relative risk, 0.75; P=0.042) and younger age at the time of pregnancy (relative risk, 0.76; P=0.022). Graft failure rate from transplantation to end of follow-up did not differ between the pregnant and nonpregnant groups (19% vs. 21%, P=0.688). The 10-year graft survival rates were also similar in the 11 women who became pregnant less than or equal to 12 months after transplantation and the 37 who became pregnant more than 12 months after transplantation (78.8% vs. 78.6%, P=0.941).
A younger age at transplantation and at pregnancy was associated with a greater likelihood of a live birth. Transplantation to conception interval of less than 1 year was not associated with a greater number of adverse pregnancy events when compared with the group with transplantation to conception interval greater than 1 year.
Background An association between the
DD allele of the angiotensin-converting enzyme gene and a poorer outcome in patients with heart failure has been found in whites. The
DD allele frequency is ...lower in Chinese, but the M235T variant of the angiotensinogen gene is more common in Chinese than whites; it is not known to what extent polymorphisms of the renin-angiotensin system affect clinical status or prognosis in Chinese patients with heart failure.
Methods We assessed the relations among polymorphism of the angiotensin-converting enzyme gene, angiotensinogen M235T (AGT) gene, and angiotensin type I receptor A1166C gene with left ventricular systolic function, left and right ventricular diastolic function, serum angiotensin-converting enzyme, plasma aldosterone and atrial natriuretic peptide levels at presentation, and clinical outcome at 1 year (survival, hospital admissions) in a cohort of Chinese patients with typical systolic heart failure (n = 82).
Results We confirmed the low prevalence of the angiotensin-converting
DD and the angiotensin type I receptor CC genotypes, and high prevalence of the AGT TT genotype in Chinese subjects compared with whites. There was no relation between the various gene polymorphisms and survival at 1 year assessed by multiple regression or Cox regression survival analysis. The AC variant of the angiotensin type I receptor gene was associated with morbidity over a 1-year period (hospital admissions) and increased baseline aldosterone levels, but none of the other polymorphisms correlated with systolic or diastolic function, aldosterone or atrial natriuretic peptide levels. By multiple regression for effects on mortality rate, only atrial natriuretic peptide and age were significant.
Conclusions In Chinese patients with heart failure, polymorphisms of the renin-angiotensin system do not appear to be related to survival or severity, probably because of the different prevalence of these genotypes in the Chinese. Thus this study illustrates that large interethnic differences in the frequencies of genotype polymorphisms of the renin-angiotensin system exist and results from one ethnic group cannot be extrapolated to another. (Am Heart J 1999;137:653-7.)
Background: The effect of N-acetylcysteine (NAC) to prevent contrast nephropathy (CN) in patients with moderate to severe renal insufficiency undergoing coronary angiography or interventions is not ...clear. Methods: This is a prospective, open-label, randomized, controlled trial. Ninety-one consecutive patients with a serum creatinine level of 1.69 to 4.52 mg/dL (149 to 400 μmol/L) undergoing coronary procedures were recruited and randomly assigned to administration of either oral NAC, 400 mg, thrice daily the day before and day of the contrast procedure (the NAC group) or no drug (the control group). Serum creatinine was measured before and 48 hours after contrast exposure. The primary end point of this study was the development of CN, defined as an increase in serum creatinine concentration of 0.5 mg/dL or greater (≥44 μmol/L) or a reduction in estimated glomerular filtration rate (GFR) of 25% or greater of the baseline value 48 hours after the procedure. Results: There were no significant differences between the 2 groups (46 patients, NAC group; 45 patients, control group) in baseline characteristics or mean volume of contrast agent administered. Six patients (13.3%) in the control group and 8 patients (17.4%) in the NAC group developed CN (P = 0.8). Serum creatinine levels increased from 2.27 ± 0.54 to 2.45 ± 0.65 mg/dL (201 ± 48 to 217 ± 57 μmol/L; P = 0.003) in the NAC group and 2.37 ± 0.61 to 2.40 ± 0.70 mg/dL (210 ± 54 to 212 ± 62 μmol/L; P = 0.6) in the control group. The increase in serum creatinine levels between the 2 groups had no difference (P = 0.7). Estimated GFR decreased from 30.3 ± 8.4 to 28.1 ± 8.4 mL/min (P = 0.01) in the NAC group and 28.4 ± 8.6 to 27.5 ± 8.8 mL/min (P = 0.3) in the control group. The decline in estimated GFR between the 2 groups had no difference (P = 0.7). Conclusion: In the current study, oral NAC had no effect on the prevention of CN in patents with moderate to severe renal insufficiency undergoing coronary angiography or interventions. However, the sample size of our present study is small. Our findings highlight the need for a large-scale, randomized, controlled trial to determine the exact beneficial effect of NAC.
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