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Background: Treatment of steroid-resistant (SR) primary focal segmental glomerulosclerosis (FSGS) remains a major challenge in nephrology. A prospective study was conducted to clarify the therapeutic role of low-density lipoprotein apheresis (LDL-A) in 11 nephrotic children with SR and cyclosporine A (CsA)-resistant primary FSGS., Methods: Based on entry criteria, all 11 eligible patients had biopsy-proven primary FSGS presenting with nephrotic syndrome (NS) and were resistant to steroid and conventional-dose CsA therapy. LDL-A was performed twice a week for 3 weeks (first course), then weekly for 6 weeks (second course). Beginning from the second LDL-A course, a dosage of 1 mg/kg/d of prednisone was administered for 6 weeks, then tapered., Results: Seven patients experienced remission of NS, 5 of whom achieved complete remission within 4 weeks after initiating prednisone therapy with LDL-A. These 5 patients maintained normal renal function during follow-up (median, 4.4 years). Of 2 patients with partial remission, 1 patient maintained stable renal function during follow-up (4.5 years), whereas the other patient showed a gradual decline in renal function and progressed to end-stage renal failure (ESRF) 7.8 years after LDL-A therapy. Four patients who were considered to experience treatment failure had persistent NS and progressed to ESRF in 1.3 years (median) after LDL-A therapy. Complete remission (n = 5) was associated with significantly more highly selective proteinuria compared with treatment failure (n = 4)., Conclusion: This study suggests that combined LDL-A and prednisone therapy can be a valuable addition to therapeutic options for treating patients with SR-FSGS. The role of LDL-A in treating these patients deserves to be assessed further in larger randomized controlled trials.

To clarify the therapeutic role of plasmapheresis (PP) for patients with Henoch-Schönlein purpura (HSP) nephritis, the clinical courses of nine children with a rapidly progressive type of HSP nephritis, who were treated with PP as the sole therapy, were retrospectively evaluated. All patients had nephrotic-range proteinuria (4.9 +/- 2.5 g/m2/d, mean +/- SD) and decreased glomerular filtration rate (GFR) (46.5 +/- 9.5 mL/min/1.73 m2) at the time of the initiation of PP. Biopsy specimens taken before PP showed large crescents involving more than 50% of the glomerular circumference in 56.8 +/- 6.9% of the glomeruli examined. The mean interval between disease onset and initiation of PP was 39.1 +/- 22.1 days. The PP regimen consisted of thrice-weekly treatment for 2 weeks, then weekly treatment for 6 weeks. No patients received any steroids or cytotoxic drugs, except for the use of steroids to manage severe abdominal pain. All patients responded promptly to PP with improvement in renal function, reduction of proteinuria, and subsidence of purpuric rash and abdominal pain. Six of nine patients showed further improvements without any other treatments; four had complete recovery, and two had only microscopic hematuria at the latest observation (follow-up period, 9.6 +/- 4.3 years). The remaining three patients showed a rebound increase of proteinuria after completion of PP; two of whom progressed to end-stage renal failure at 14.1 years and 1.8 years after disease onset. Because all patients had the most severe forms of nephritis, reported to carry a grave prognosis, this study suggests that PP as the sole therapy is effective in improving the prognosis of patients with rapidly progressive HSP nephritis, particularly if instituted early in the course of the disease. The role of PP in treating HSP nephritis deserves to be assessed further in larger randomized controlled trials.

The left atrial (LA) function during coronary artery occlusion followed by reperfusion using densitometric analysis of digital atrioventriculographic images was evaluated. Eight anesthetized dogs underwent atrioventriculography at baseline, 10 and 60 min after left circumflex coronary artery (LCX) occlusion and 5, 30, 60, and 120 min of reperfusion. Time-density curves were obtained for LA and left ventricle (LV). The ratios of passive atrial video-densitometric change (VC) to total VC (Passive Ratio), and active VC to total VC (Active Ratio) were calculated. Left ventricular ejection fraction (LVEF), peak ejection rate (PER), and peak filling rate (PFR) were derived. Active Ratio, an index of atrial contraction, increased to 144%, and Passive Ratio decreased to 75% of baseline at 60 min of LCX occlusion. Two hours after reperfusion, both Active and Passive Ratios returned to control level. While LVEF reduced to 70%, PER to 67%, LV peak positive dP/dt to 88% of baseline at 60 min after occlusion, and remained depressed at 2 h after reperfusion. However, PFR, LV peak negative dP/dt and LV isovolumic pressure decay rate showed recovery at 2 h after reperfusion. There were significant correlations between PFR and Passive Ratio (r = 0.41), and between Active and Passive Ratios (r = 0.55). Thus, time-course of recovery of LV post-ischemic systolic and diastolic function was different. Return of LA function to control level during 2 h after reperfusion may be depend on recovery of LV diastolic function.

Results of recent animal studies have lent support to the hypothesis that hyperlipidaemia may contribute to renal injury. This report documents the case of a 15-year-old boy with drug-resistant nephrotic syndrome due to focal segmental glomerulosclerosis (FGS) who showed an improvement in renal function and proteinuria as a result of treatment with low-density lipoprotein aphaeresis (LDL-A) combined with pravastatin. Although further work is required to determine the efficacy of lipid-lowering therapy in progressive glomerular disease in humans, the combination of LDL-A and pravastatin is likely be included in the choice of treatment modalities available for patients with drug-resistant nephrotic syndrome due to FGS.

To assess the left ventricular (LV) global and regional (anterior, apical, inferior) diastolic filling dynamics in compensated dilated cardiomyopathy (DCM), we measured left ventricular pressure and instantaneous volume from angiography in 7 normal controls (CTL) and 6 DCM patients with sinus rhythm. Global and regional peak filling rate (PER), time constant of LV pressure decline (T; Weiss's method) and LV chamber stiffness (k; Gaasch's method) were calculated. In DCM, left ventricular end-diastolic volume (ml/m2) was larger than in CTL (137 +/- 29 vs. 74 +/- 6, p less than 0.001), and stroke index (ml/m2) was not different from CTL (46 +/- 14 vs. 46 +/- 8, NS), indicating a compensated state of LV. Mitral valve opening pressure (mmHg) tended to increase in DCM compared with CTL (12 +/- 6 vs. 8 +/- 4). Global PFR (ml/sec/m2) (CTL = 216 +/- 47 vs. DCM = 201 +/- 36) and k (CTL = 0.044 +/- 0.023 vs. DCM = 0.029 +/- 0.016) were not different between 2 groups. However, T (msec) was markedly prolonged in DCM compared with CTL (61 +/- 10 vs. 35 +/- 5, p less than 0.001). In CTL, regional PFR (1/sec) showed almost the same values in each region, but in DCM, apical region showed higher PFR than in other regions. Thus, early diastolic filling might play an important role in maintaining the total transmitral flow in DCM despite severe impairment of LV relaxation. This compensation could be related mainly to accelerated regional lengthening of the LV apical region.

DMG, a new polysaccharide with a well-characterized structure, isolated from the culture filtrate of an actinomycetes and then degraded by acid treatment, was tested for antitumor activity on allogeneic and syngeneic tumors in mice. In the allogeneic Ehrlich solid tumor system, DMG showed antitumor activity over a wide dose range, its optimal dose being 10-100 mg/kg. The optimal time of DMG administration was 1-2 weeks after tumor inoculation, but DMG was also effective when given before tumor inoculation. DMG was effective when given ip, sc, it (intratumorally) or iv. DMG also had antitumor effects on syngeneic tumors. It rapidly inhibited the growth of MM46 mammary carcinoma, MH134 hepatoma, and Meth A fibrosarcoma, and also inhibited spontaneous pulmonary metastases of B16-BL6 melanoma. However, it had no direct cytocidal action on tumor cells in vitro. Its antitumor activity was much less in athymic nude mice and in mice immunosuppressed by whole-body X-irradiation than in normal hosts.Thus, DMG was shown to exert antitumor activity via host-mediated mechanisms. Its antitumor activity is discussed in comparison with those of other antitumor polysaccharides.

To assess the degree of collateral vessels after myocardial infarction, coronary angiograms, left ventriculograms, and exercise thallium-201 myocardial scintigrams of 36 patients with previous myocardial infarction were reviewed. All 36 patients had total occlusion of infarct-related coronary artery and no more than 70% stenosis in other coronary arteries. In 19 of 36 patients with transient reduction of thallium-201 uptake in the infarcted area during exercise (Group A), good collaterals were observed in 10 patients, intermediate collaterals in 7 patients, and poor collaterals in 2 patients. In 17 of 36 patients without transient reduction of thallium-201 uptake in the infarcted area during exercise (Group B), good collaterals were seen in 2 patients, intermediate collaterals in 7 patients, and poor collaterals in 8 patients (p less than 0.025). Left ventricular contractions in the infarcted area were normal or hypokinetic in 10 patients and akinetic or dyskinetic in 9 patients in Group A. In Group B, 1 patient had hypokinetic contraction and 16 patients had akinetic or dyskinetic contraction (p less than 0.005). Thus, patients with transient reduction of thallium-201 uptake in the infarcted area during exercise had well developed collaterals and preserved left ventricular contraction, compared to those in patients without transient reduction of thallium-201 uptake in the infarcted area during exercise. These results suggest that the presence of viable myocardium in the infarcted area might be related to the degree of collateral vessels.