The Hong Kong Society of Rheumatology consensus recommendations for the management of gout

Clinical Rheumatology - Gout is one of the most common noncommunicable diseases in Hong Kong. Although effective treatment options are readily available, the management of gout in Hong Kong remains...     

Normal growth of prepubertal nephrotic children during long-term treatment with repeated courses of prednisone

The growth of 21 prepubertal children with steroid-dependent frequently relapsing nephrotic syndrome was studied before and during treatment with repeated courses of oral prednisone for 4 y. The height and height velocity standard deviation scores (HSDS and HVSDS) of the nephrotic children were -0.11 and -0.06, respectively, at the onset of the disease and -0.12 and +0:05, +0:14 and +1:02, +0:21 and +0:78 and +0:17 and +0:66, respectively, thereafter yearly during the treatment. The mean yearly cumulative dose of prednisone was 6300, 3459, 2677 and 2081 mg/body area (m) at the first, second, third and fourth year, respectively. The nephrotic children grew normally for their age before onset of the disease and growth remained normal despite prednisone treatment.     

Characterization of the p67phox gene: genomic organization and restriction fragment length polymorphism analysis for prenatal diagnosis in chronic granulomatous disease

The genetic defect in the p67phox-deficient form of chronic granulomatous disease (CGD) follows an autosomal recessive pattern of inheritance. When genomic DNA from normal individuals is digested with HindIII and probed with p67phox cDNA an allelic restriction fragment length polymorphism (RFLP) of 4.0 kb or 2.3 kb is detected. We cloned and characterized the p67phox gene using the cDNA and sequenced the exon/intron boundaries, mapping 16 exons on the 40-kb gene. The polymorphic region was then sequenced to identify the inheritance pattern of amniocentesis-derived fetal cells by genomic amplification. The proband, a 9-year-old female patient with p67phox-deficient CGD, and her phenotypically normal mother are homozygous for the RFLP marker, whereas the father and two brothers are heterozygous. The fetus was shown to be heterozygous as well, showing it had inherited at least one normal p67phox gene from the father and that it was predicted to have a normal phenotype. Cord blood samples at birth showed normal oxidative function. Amplification allows rapid detection of the inheritance pattern for fetal diagnosis in informative families. We report the genomic structure of p67phox and an amplification-based method for detection of the marker on chromosome 1q25, used here for prenatal diagnosis of CGD.     

Three-year randomized controlled trial of dipyridamole and low-dose warfarin in patients with IgA nephropathy and renal impairment

Summary: Activation of platelets and the coagulation pathway are factors which may contribute to the progression of renal disease in IgA nephropathy (IgAN). Of 21 patients with IgAN and serum creatinines between 1.6 and 3.0 mg/dL, 10 were assigned to treatment with dipyridamole and low-dose warfarin (keeping the thrombotest between 30 and 50%) and 11 to no treatment in a prospective randomized 3-year study. At entry into the trial, patients in the treatment group were younger (35 ± 6 years vs 42 ± 9 years) and had worse histological scores for tubular atrophy (1.7 ± 0.7 vs 1.1 ± 0.5) and arteriolar hyperplasia (1.4 ± 0.7 vs 0.7 ± 0.8) than those in the non-treatment group. There were no differences in serum creatinine values, creatinine clearances, urinary protein excretions, serum albumins or urinary erythrocyte counts. At the end of the trial, patients on treatment did not experience a significant increase in serum creatinine values (1.9 ± 0.3 mg/dL to 2.5 ± 1.2) or reduction in creatinine clearances (52 ± 20mL/min to 52 ± 27). Untreated patients, however, experienced a significant rise in serum creatinine values (2.1 ± 0.5 mg/dL to 3.3 ± 1.1, P < 0.01) and a fall in creatinine clearances (51 ± 26 mL/min to 31 ± 22, P = 0.06). There was no significant change in the proteinuria in either group (treatment group: 1.2 ± 1.2 g/day to 1.3 ± 1.1, non-treatment group: 1.9 ± 1.4 to 1.5 ± 1.1) and there was also no change in serum albumins and urinary erythrocyte counts. Four untreated and one treated patient developed end-stage renal failure during the course of the trial. This study suggests that treatment of patients with IgAN and renal impairment with dipyridamole and low-dose warfarin retards the deterioration of renal function, as measured by the serum creatinine and creatinine clearance.     

参三七皂甙Rg1对实验性血栓形成的影响及其机制探讨

用大鼠动静脉血栓形成模型,研究参三七皂甙Rg₁抗血栓作用。结果表明,参三七皂甙Rg₁可明显降低实验性血栓形成,对大鼠血浆纤溶系统亦有明显作用,可升高血浆中组织纤溶酶原激活物(t-PA)活性和活性型t-PA百分比,降低组织纤溶酶原激活物抑制剂(PAI)活性。同时利用培养大鼠血管内皮细胞实验,发现Rg₁可以剂量依赖性提高血管内皮细胞一氧化氮(NO)释放。提示Rg₁抗血栓作用与增强纤溶系统活性,促进血管内皮NO释放有关。     

Adrenocorticoid regulation of Na+, K+-ATPase in adult rat kidney: effects on post-translational processing and mRNA abundance

The mechanisms by which adreno-corticoid hormones regulate Na⁺, K⁺-ATPase in adult kidney were studied in adrenalectomized (Adx) rats. Five days after adrenalectomy, Na⁺, K⁺-ATPase activity was significantly reduced in the renal cortex homogenate (C = 13.0±0.8 vs. Adx = 7.1±0.7 μmol Pi mg^-1 protein h^-1) and in renal microsomes (C = 30.3 ± 1.9 vs Adx = 14.6 ± 1.3 μmol Pi mg^-1 protein h^-1). Glucocorticoid replacement treatment of adrenalectomized rats with betamethasone (20 μg kg^-1 body wt twice daily for 5 days) effectively counteracted the observed reduction in Na⁺, K⁺-ATPase activity. In cortical homogenate the protein level of α1 and β1 subunits measured in immunoblots was not significantly different in Adx and control rats, indicating that 5 days after adrenalectomy the α1 and β1 subunits were present in renal cortical cells to almost normal extent but could not be assembled into a transmembrane functional unit. In support of this conclusion we found that the protein level of both the α1 and β1 subunits was significantly lower (P < 0.001 for both subunits) in microsomes from Adx than in control rats. The mRNA abundance for α1 and β1 subunits were not lower in Adx as compared to control rats 1 and 5 days after surgery. However, if Adx rats were given a single dose of betamethasone (600 μg kg^-1 body wt), a significant 2-fold increase in both α1 and β1 mRNAs was observed (P < 0.05 for both subunits). These data suggest that glucocorticoids can upregulate the mRNA of both Na⁺, K⁺-ATPase subunits but that the low renal Na⁺, K⁺-ATPase activity in adult Adx rats is mainly due to loss of glucocorticoid regulation of the post-translational processing of the enzyme.     

Artery blood pressure oscillation after active standing up: an indicator of sympathetic function in diabetic patients

Dynamic artery blood pressure (Finapres) response to active standing up, normally consisting of initial rise, fall and recovery above the baseline (overshoot), was compared with the early steady-state artery blood pressure level to measure sympathetic vasomotor function in healthy subjects (n=23, age 35±9 years; mean±SD) and in type I diabetic patients without autonomic neuropathy (AN) (group 1: n=18, 38±13 years), with AN but no cardiovascular drugs (group 2a: n=7, 44±11 years) and with both AN and cardiovascular drugs (group 2b: n=10, 47±7 years). Systolic and diastolic overshoot were similar in the control (15±13/15±11 mmHg) and group 1 subjects. Systolic overshoot disappeared in 57% of patients in group 2a (?1±9 mmHg; P<0·03), whereas artery blood pressure still overshot in diastole (8±7 mmHg; NS). Systolic overshoot disappeared in all patients in group 2b (?22±22 mmHg; P<0·0006) and diastolic overshoot disappeared in 60% of these patients (?6±16 mmHg; P=0·0006). Systolic early steady-state level was not lower in group 2a than in group 1 (NS), but it was impaired in group 2b (P<0·006), in which six diabetic patients had a pathological response beyond the age-related reference values. There was a strong association between the overshoot and steady-state levels (P for χ²<0·001, n=58). Overshoot of the control subjects and patients in group 2b correlated to their respective steady-state blood pressure levels (r≥0·76; P≤0·001). In conclusion, baroreceptor reflex-dependent over-shoot of the artery blood pressure after active standing up diminishes with the development of AN and it is associated with the early steady-state level of the artery blood pressure.