Kee-Lam Wong

Sequential Therapy for Diffuse Proliferative and Membranous Lupus Nephritis: Cyclophosphamide and Prednisolone Followed by Azathioprine and Prednisolone

A retrospective single-center cohort study was conducted on 35 patients with diffuse proliferative (WHO type IV) and/or membranous (type V) lupus nephritis (22 with type IV, 6 with type V, and 7 with type IV plus V) who had been treated with a sequential regimen comprising prednisolone and cyclophosphamide during active disease, followed by low-dose prednisolone and azathioprine maintenance. The follow-up period was 33.2 +/- 4.5 months. At presentation, 32 (91.4%) patients were nephrotic, and an abnormal serum creatinine level was noted in 14 (48.3%) patients with type IV changes. Cyclophosphamide was given for 26.8 +/- 2.8 weeks. 33 (94.3%) patients achieved complete or partial renal remissions: 77.3 and 22.7% of the type IV patients, 16.7 and 66.6% of the type V patients, and 14.3 and 71.4% of the type IV plus V patients, respectively (p < 0.0001 for type IV versus type V and for type IV versus type IV plus V). The duration of therapy before renal remissions and normalization of C3 were attained was similar among the three groups of patients. Disease relapse occurred in 4 (18.2%) of 22 IV patients and in 1 of the 5 type V patients in remission. Mortality was not observed, and none of the patients had an increase in serum creatinine level to double the baseline value. Adverse effects related to therapy included: hair loss (42.9%), transient amenorrhea (53.6%), leukopenia (11.4%), febrile episodes (14.3%), and herpes zoster(28.6%). We conclude that sequential use of prednisolone and cyclophosphamide followed by low-dose prednisolone and azathioprine can achieve favorable therapeutic results in the majority of patients with diffuse proliferative and/or membranous lupus nephritis, without excessive toxicities.

Doppler echocardiographic evaluation of left ventricular diastolic function in patients with systemic lupus erythematosus.

Subclinical myocardial involvement frequently occurs in patients with systemic lupus erythematosus (SLE). In this study, left ventricular diastolic function was assessed in 58 patients (54 female and 4 male; mean age 32 +/- 11 years) and in 40 sex-matched and age-matched healthy control subjects (37 female and 3 male; mean age 33 +/- 9 years) by means of pulsed Doppler echocardiography. All subjects had no clinical evidence of overt myocardial disease or abnormal left ventricular systolic function. Compared with the control group, patients with SLE had significantly prolonged isovolumic relaxation time (62 +/- 12 vs 80 +/- 14 msec; p less than 0.01), reduced peak early diastolic flow velocity (peak E) (82 +/- 18 vs 76 +/- 16 cm/sec; p less than 0.05), increased peak late diastolic flow velocity (peak A) (45 +/- 7 vs 53 +/- 8 cm/sec; p less than 0.01), reduced E/A ratio (1.81 +/- 0.32 vs 1.46 +/- 0.29; p less than 0.001), and lower deceleration rate of early diastolic flow velocity (EF slope) (489 +/- 151 vs 361 +/- 185 cm/sec2; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac abnormalities in systemic lupus erythematosus: a prospective M-mode, cross-sectional and Doppler echocardiographic study

A prospective M-mode, cross-sectional and Doppler echocardiographic study was performed on 75 patients with systemic lupus erythematosus and 60 sex- and age-matched control subjects. Compared with the control group, patients with lupus had an increased prevalence of echocardiographic abnormalities. These included pericardial effusion and/or thickening (37%), left ventricular hypertrophy (12%), global left ventricular hypokinesis (5%), segmental abnormalities of left ventricular wall motion (4%), right ventricular enlargement (4%), focal verrucous valvar thickening (12%), gross valvar thickening and dysfunction (8%), mitral regurgitation (25%) and aortic regurgitation (8%). Two patients with gross mitral valvar thickening and dysfunction subsequently underwent valvar replacement. Correlation between echocardiographic abnormalities and clinical parameters showed that pericardial effusion was significantly associated with pericardial pain (P less than 0.05) and active disease (P less than 0.001), and left ventricular hypertrophy with systemic hypertension (P less than 0.05). Thus, there was a high prevalence of cardiac abnormalities, especially pericardial and valvar lesions, in patients with systemic lupus erythematosus. Echocardiography is invaluable in identifying these abnormalities and should be used routinely for cardiac evaluation of these patients.

Lack of association between slow acetylator status and spontaneous lupus erythematosus

The Chinese in Southeast Asia are recognized as a population group that has a relatively high prevalence of rapid “acetylators” and a relatively high incidence of systemic lupus erythematosus. This study was designed to evaluate the possibility that there were environmental lupus erythematosus provocative substances eliminated by acetylation that resulted in a preponderance of slow acetylators among patients with the disease. We compared acetylator status in 36 Chinese women with mild, stable, and confirmed lupus erythematosus and 36 healthy control subjects matched for age, sex, and ethnic origin. Acetylator status was determined by use of HPLC to assay 5‐acetylanimo‐6‐formylamino‐3‐methyluracil/methylxanthine (AFMU/MX) and AFMU/(AFMU + MX) ratios in urine 1 to 4 hours after drinking a strong cup of coffee (caffeine). By use of parametric and nonparametric methods of analysis, the frequency distribution of AFMU/MX and AFMU/(AFMU + MX) ratios in both the patients and control subjects were determined to be very similar. Thus there was no association between slow acetylator status and lupus erythematosus in the study subjects.

Crescentic IgA glomerulonephritis following interleukin-2 therapy for hepatocellular carcinoma of the liver

A patient who developed crescentic IgA nephropathy following treatment with recombinant interleukin-2 (rIL2) and lymphokine-activated killer (LAK) cell therapy for hepatocellular carcinoma was reported. Cessation of rIL2 and LAK cell treatment plus plasmapheresis and steroid therapy was successful in achieving partial improvement and stabilization of renal function. This is the first case report of biopsy-documented glomerulonephritis developing after IL2 and LAK cell therapy. This provides indirect in vivo evidence for the role of IL2 in mediating glomerular injury in IgA nephropathy.

Doppler-Echo Evaluation of Left Ventricular Diastolic Filling in Patients with Mixed Connective Tissue Disease

Left ventricular diastolic function was assessed in 17 patients (2 males and 15 females; mean age 44 +/- 9 years) with mixed connective tissue disease (MCTD) and 18 sex- and age-matched healthy control subjects (2 males and 16 females; mean age 44 +/- 8 years) by means of M-mode and pulsed Doppler echocardiography. None had clinical evidence of overt myocardial disease or abnormal left ventricular systolic function. Compared with the control group, patients with MCTD had a significantly longer isovolumic relaxation time (IVRT) (59 +/- 7 versus 70 +/- 12 ms; p less than 0.01), a lower peak early diastolic flow velocity (E) (0.79 +/- 0.10 versus 0.70 +/- 0.07 m/s; p less than 0.005), a higher peak late diastolic flow velocity due to atrial contraction (A) (0.47 +/- 0.08 versus 0.54 +/- 0.08 m/s; p less than 0.05) and a reduced E/A ratio (1.72 +/- 0.37 versus 1.33 +/- 0.26; p less than 0.005). Although there was no significant correlation of left ventricular diastolic filling indexes with age, heart rate, left ventricular end-diastolic and end-systolic dimensions, interventricular septal and left ventricular posterior wall thickness, and fractional shortening, the duration of illness was significantly related to IVRT (r = 0.62; p less than 0.01), peak A (r = 0.79; p less than 0.001) and velocity half-time (r = 0.54; p less than 0.05). The results suggest the presence of an abnormal left ventricular diastolic filling pattern in patients with MCTD and may represent myocardial involvement in this disease.

Sulpiride improves functional dyspepsia: A double‐blind controlled study

A 4‐week placebo‐controlled trial was performed to study the efficacy of sulpiride, a hypothalamic non‐sedative neuroleptic and dopamine antagonist, in the treatment of 100 patients with functional dyspepsia, defined as dyspeptic symptoms despite normal endoscopy and cholecystography. Two patients on sulpiride were withdrawn because of sleepiness; no other undue side effects were recorded. At the end of 4 weeks, significantly (P < 0.02) more patients on sulpiride had improvement of nausea and belching (78%, 54% respectively) than patients on placebo (45%, 17% respectively). Pain and vomiting disappeared in approximately 50% and 70% of patients, respectively. In the overall assessment, 72% and 39% of the patients on sulpiride and placebo respectively had satisfactory improvement or became symptom‐free (P < 0.001). Response to treatment was not related to personal and environmental factors. It was concluded that sulpiride was effective in improving symptoms of dyspepsia, particularly nausea and belching.

Association between antiphospholipid antibodies and cardiac abnormalities in patients with systemic lupus erythematosus

PURPOSE Although the antiphospholipid antibodies are well recognized to be associated with thrombosis, recurrent abortion, and thrombocytopenia in patients with systemic lupus erythematosus (SLE), their relationship with cardiac disease is less clear. The purpose of this study was to evaluate the association between anti-phospholipid antibodies and cardiac abnormalities in patients with SLE. PATIENTS AND METHODS A total of 75 consecutive SLE patients and 60 healthy sex- and age-matched control subjects were evaluated in a case-control study. All participants underwent M-mode, two-dimensional, and Doppler echocardiography. Antiphospholipid antibodies levels were assayed in each patient. The prevalence of antiphospholipid antibodies in patients with and without echocardiographic abnormalities was compared. RESULTS Compared with the control group, SLE patients had significantly more pericardial abnormalities, left ventricular hypertrophy, left atrial enlargement, left ventricular dysfunction and verrucous valvular thickening, global valvular thickening with dysfunction, and mitral and aortic regurgitation. Among these abnormalities, antiphospholipid antibodies were significantly associated with isolated left ventricular (global or segmental) dysfunction (four of five positive; p less than 0.05), verrucous valvular (mitral or aortic) thickening (seven of nine positive; p less than 0.005), global valvular (mitral or aortic) thickening and dysfunction (five of six positive; p less than 0.02), as well as mitral regurgitation (16 of 19 positive; p less than 0.001) and aortic regurgitation (five of six positive; p less than 0.02). CONCLUSION Valvular lesions and myocardial dysfunction are associated with elevated antiphospholipid antibodies. This study has important implications for the pathogenic role of anti-phospholipid antibodies in relation to these cardiac abnormalities.