Crescentic glomerulonephritis developing 3 months after autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

A 64-year-old woman underwent an ileocecal resection for ileus. The specimen revealed a diffuse large B cell lymphoma. The diagnosis was stage IIA non-Hodgkin's lymphoma. She received chemotherapy with the CHOP-etoposide regimen, resulting in partial remission. High-dose etoposide was used for PBSC mobilization before auto-PBSCT. Conditioning was ranimustine, carboplatin, etoposide and cyclophosphamide. Her renal function deteriorated gradually, starting 3 months post-PBSCT. Eight months post-transplant, serum creatine concentration was 7.1 mg/dl, and BUN was 59.2 mg/dl. Her hemoglobin concentration decreased to 5.3 g/dl, with no evidence of hemolysis. Renal biopsy revealed fibrous crescent formations in glomeruli, and mononuclear cell infiltration in interstitial spaces. Renal injury in this patient differs from BMT nephropathy, which is similar to hemolytic uremic syndrome, and represents another type of late renal injury after PBSCT.

Expression of tenascin in mesangial injury in experimental glomerulonephritis.

The distribution of tenascin (TN) in the kidneys in relation to embryogenesis, the normal glomerulus and various glomerular diseases has been studied immunohistochemically. However, the existence of TN protein and mRNA simultaneously has never been reported in reversible mesangial proliferative glomerulonephritis (MPGN). In this study, by immunohistochemical methods and in situ hybridization, we investigated the expression of TN in injury to glomerular mesangial cells. Anti-Thy 1.1 mesangial proliferative glomerulonephritis was induced in Wistar rats by injection of antirat thymocyte plasma. After injection, the rats were sacrificed on days 4, 7, 10 and 14. Immunohistochemically, slight staining of TN was detected in normal glomeruli. An increase in staining was observed in the mesangial areas during the mesangial proliferative phase (days 4, 7 and 10). It decreased on day 14. Focal staining of TN in Bowman's capsule and the periglomerular region was also noted during the mesangial proliferative phase. TN mRNA could not be detected in normal glomeruli by in situ hybridization, but it was observed in the mesangial areas during the mesangial proliferative phase. Focal expression of TN mRNA was noted in Bowman's capsular epithelial cells and periglomerular cells after injection. TN mRNA-positive cells were localized to mesangial, Bowman's capsular and periglomerular areas of hypercellularity and were significantly associated with an increase in TN staining areas. In conclusion, the results of this study prove that TN is a component of the normal mesangial matrix, and that it is induced by mesangial, Bowman's capsular and periglomerular cells after mesangial injury. We could not determine the role of TN in Bowman's capsular and periglomerular areas, but a reversible MPGN model has been reported to show an irreversible progressive course in TN knockout mice. In reversible MPGN it is considered that the role of TN in the mesangial areas may be related to the process of mesangial repair.

Changes in glomerular epithelial cells induced by FGF2 and FGF2 neutralizing antibody in puromycin aminonucleoside nephropathy.

In the present study, two series of experiments were done with PAN nephropathy rats given fibroblast growth factor 2 (FGF2) or FGF2 neutralizing antibodies. In the first series of experiments, a dose of 10 micrograms of FGF2 (FGF2 group), 40 micrograms of an FGF2 neutralizing antibody (Anti-FGF2 group) or an equal volume of physiological saline (Control group) was administered for four days after PAN injection. Urinary protein increased more in the FGF2 group than in the other two groups. PCNA (+) glomerular cells were found in decreasing order in groups FGF2, Control and Anti-FGF2. Most of the PCNA (+) cells were podocytes and epithelial cells of Bowman's capsule. Staining for desmin, a marker of podocyte injury, was significantly reduced in the Anti-FGF2 group. Glomerular adhesive lesions were found in decreasing order in groups FGF2, Control and Anti-FGF2. The second series of experiments was designed to study the effects of FGF2 neutralizing antibody (40 micrograms for 5 days after PAN injection, in MoAb group) on severely damaged podocytes caused by repeated (two courses) injections in the PAN nephropathy rats. The results were the same as those in series 1. An increase in urinary protein excretion was observed in both groups, but on the 40th day, the level of proteinuria in the MoAb group decreased abruptly. It was observed that the MoAb group had few adhesive glomeruli compared to the IgG group (administration of mouse IgG) and the PCNA (+) epithelial cells of Bowman's capsule were also few. It was supposed that FGF2 would promote the formation of adhesive lesions by stimulating the proliferation of podocytes and epithelial cells of Bowman's capsule. Additionally, FGF2 itself was thought to impair podocytes because of the increasing desmin score and proteinuria.

[Expression of FGF2, FGF receptor-1 and alpha-smooth muscle actin in experimental mesangial proliferative nephritis].

Mesangial cell (MC) proliferation is the principal cause of glomerulonephritis and glomerulosclerosis. Previous studies have demonstrated that various cytokines and growth factors are MC mitogens. In vitro, basic fibroblast growth factor (FGF2) stimulates MC proliferation. In the present study, two series of experiments were conducted using rats with anti-Thy 1.1 mesangial proliferative glomerulonephritis. The first series of experiments was designed to clarify the expression relationship between FGF2, FGF, receptor-1 (FGFR1) and alpha-smooth muscle actin (alpha-SMA). The second series examined the effect of intravenous administration of recombinant FGF2 in this model. The first series involving in situ hybridization with FGF2 and FGFR1 cRNA probes, showed that these mRNAs were expressed in the mesangial areas during the proliferative phase (days 4-7). Simultaneously, the alpha SMA scores of glomeruli also increased. In the second series, FGF2 was administered at 6, 12 and 24 hours (early group) and at 4, 5, and 6 days (late group) after disease induction. On day 7, there were more glomerular cells positive for proliferative cell nuclear antigen (PCNA) in the late group than in the control and early groups and the alpha-SMA scores of the glomeruli had increased in the late group. On day 14, the number of mesangial cells mainly increased in the late group. These findings suggest that FGF2 and FGFR1 showed significant correlation with the phenotypic changes of MC.

[A case of renovascular hypertension with nephrotic syndrome].

A 68-year-old male patient with renovascular hypertension (RVHT) and nephrotic syndrome (NS) is described. He was admitted to our hospital for detailed investigation of severe hypertension and massive proteinuria. After admission, a diagnosis of RVHT with a right non-functional kidney and NS was made. Nephrectomy and contralateral renal biopsy were performed for refractory hypertension and detailed investigation of the NS, respectively. The renal biopsy showed focal segmental glomerulosclerosis (FGS) in the left kidney, whereas the nephrectomised kidney exhibited only ischemic change. After the operation, his blood pressure became stable without anti-hypertensive agents, but proteinuria remained in the nephrotic range. Six months later, proteinuria had disappeared and his renal function was stable. These findings suggest that NS and FGS might have resulted from an activated renin-angiotensin-axis and that the prolonged NS was due to severe glomerular injury. Although there have been many reports describing the relationship between RVHT and FGS in an experimental environment, this relationship is very rare in clinical cases. Therefore we present this case to increase understanding of the cause of FGS.

[Doppler techniques in the detection of valvular regurgitation: their value and limitations].

To evaluate the clinical value of various Doppler techniques in detecting valvular regurgitation, we compared the sensitivity, timing and duration of regurgitation, and the peak velocity of regurgitant signals among conventional pulsed Doppler, color Doppler, continuous wave Doppler and HPRF Doppler echocardiography. 1. Sensitivity of Doppler techniques in detecting mitral regurgitation: Among fifty patients with mitral regurgitation confirmed by left ventriculography, mitral regurgitation was detected in 48 (96%) using color Doppler and pulsed Doppler echocardiography; in 41 (82%) by HPRF Doppler; and in 37 (74%) by continuous wave Doppler echocardiography. In 103 consecutive normal volunteers, mitral regurgitant signals were detected in 46 (45%) by color Doppler, in 39 (38%) by pulsed Doppler, in 16 (16%) by HPRF Doppler, and in 8 (8%) by continuous wave Doppler echocardiography. 2. Timing and duration of regurgitant signals: To assess the timing and duration of regurgitant signals, 43 patients with regurgitant signals of short duration during systole or diastole were studied using M-mode color Doppler echocardiography. Using the latter method, regurgitant signals throughout systole and the isovolumic relaxation period could be demonstrated in all but four patients who had regurgitant signals of short duration during systole, but suggesting mitral or tricuspid regurgitation. In all patients with regurgitant signals of short duration during diastole, aortic or pulmonary regurgitant signals throughout diastole could be demonstrated with M-mode color Doppler echocardiography. Thus, this technique is superior to conventional pulsed Doppler echocardiography for detecting accurate timing and duration of valvular regurgitation. 3. Peak velocity of regurgitant flow: To compare the peak velocity of regurgitant flow by continuous wave Doppler and by HPRF Doppler echocardiography, 20 patients with mitral regurgitation and 22 patients with tricuspid regurgitation were examined using the both methods. In patients with severe mitral regurgitation, the peak velocity detected by HPRF Doppler echocardiography correlated well (r = 0.96) with that detected by continuous wave Doppler echocardiography. However, in patients with mild mitral regurgitation, the peak velocity detected by HPRF Doppler echocardiography was higher than that detected by continuous wave Doppler echocardiography. In patients with severe tricuspid regurgitation, the peak velocity had a close correlation (r = 0.99) with the both techniques. In patients with mild tricuspid regurgitation, the peak velocity was higher by HPRF than by continuous wave Doppler echocardiography. In conclusion, color or pulsed Doppler echocardiography should be used for detecting valvular regurgitation. M-mode color Doppler echocardiography is superior to conventional pulsed Doppler echocardiography for detecting timing and duration of valvular regurgitation.(ABSTRACT TRUNCATED AT 400 WORDS)

Color Doppler evaluation of valvular regurgitation in normal subjects.

To determine prospectively the prevalence of mitral, aortic, tricuspid, and pulmonary regurgitation in normal persons, 211 consecutive, apparently healthy volunteers were examined with a color Doppler flow imaging system. The subjects were divided into five age groups (group 1, 6-9 years old; group 2, 10-19 years old, group 3, 20-29 years old, group 4, 30-39 years old, and group 5, 40-49 years old). The prevalence rate of mitral regurgitation in the normal subjects was 38-45% in each group. The mitral regurgitant jets came from the posteromedial commissure in all but two subjects. No aortic regurgitant flow signals were detected in the normal subjects. Tricuspid regurgitation was detected in 15-77% in each group, and pulmonary regurgitation was detected in 28-88%. Regarding the tricuspid and pulmonic valves, the prevalence rate of regurgitation is age dependent (p less than 0.01) and tends toward the lower rate in groups over the age of 30 years. The tricuspid and pulmonary regurgitant jets came from the center of the coaptation of each valve. The area of the regurgitant jet signals in normal persons was significantly smaller (p less than 0.001) than that obtained from patients with organic valve disease. Our study shows that in a large proportion of normal persons under the age of 50 years color Doppler echocardiography permits recording of regurgitant signals behind all valves except the aortic. In conclusion, one should be aware of the existence and characteristics of regurgitation in normal persons when evaluating valvular regurgitation by Doppler techniques.

Problems in the management of elderly patients with valvular heart disease.

One hundred and nine patients over the age of 65 years with valvular heart disease have been reviewed. Of these, 57 patients were treated medically (medical group) and the remaining 52 patients underwent valve surgery (surgical group). Of the 57 patients who were treated medically, 46 (81%) were in NYHA Functional Class I or II, 7 were in Class III, and 4 were in Class IV. Among these, there were 8 deaths. The 5 year survival rate of the medical group, calculated by the actuarial method, was 90 +/- 5%. Eight patients had a nonfatal cerebrovascular accident. Of the 52 elderly patients who underwent valve surgery, 20 were in NYHA Functional Class II, 21 were in Class III, and 11 were in Class IV. Of these, there were 5 operative deaths (9.6%). Four patients died of postoperative low cardiac output syndrome and renal failure. One died of intraoperative aortic dissection. Of the 470 patients under the age of 65 years, there were 15 operative deaths (3.2%). Forty-one of the 47 hospital survivors have improved their cardiac functional classification, while 6 patients have remained in the same class as preoperatively. The average NYHA Class prior to operation was 2.7 improved to Class 1.3 after operation. The 3 year survival rate of the surgical group, calculated by the actuarial method, was 81 +/- 6%. Thus, the prognosis of asymptomatic elderly patients is good. Although operative mortality for the symptomatic elderly patients is relatively high, valve surgery can be performed with a satisfactory prognostic outlook.

[Late complications of valve replacement: the benefits of non-invasive assessment].

Non-invasive techniques were assessed for their capabilities of detecting prosthetic valve malfunctions in 70 consecutive patients with angiographically-documented or surgically-proven prosthetic valve dysfunction. Their 74 dysfunctioning valves were studied using phonocardiography, M-mode and two-dimensional echocardiography and Doppler methods, including pulsed and continuous wave (CW) Doppler echocardiography and two-dimensional Doppler color flow mapping (2DD). These results were compared among the examinations, and also compared between 43 patients with 44 dysfunctioning mechanical valves and 27 patients with 30 dysfunctioning bioprosthetic valves. Symptoms related to valve malfunction were recognized in all patients with prosthetic valve endocarditis and in all patients but one with stenotic condition. In patients with valvular regurgitation, however, symptoms were observed in only six of the 21 patients with mechanical prostheses and in 12 of the 25 patients with bioprosthetic valves (p less than 0.01). Among 43 patients with 44 mechanical valve dysfunctions, the sensitivities of phonocardiography, M-mode and two-dimensional echocardiography and Doppler techniques were 85, 65 and 86 percent, respectively, in 20 patients with stenosis; 100, 57 and 80 percent in seven patients with transvalvular regurgitation; and 100, 50 and 100 percent in 14 patients with paravalvular regurgitation. Similarly, among 27 patients with bioprosthetic valve dysfunctions, the sensitivities of phonocardiography, M-mode and two-dimensional echocardiography and Doppler methods were 67, 100 and 100 percent, respectively, in three patients with stenotic condition; 85, 65 and 100 percent in 20 patients with transvalvular regurgitation; and 60, 40 and 100 percent in five patients with paravalvular regurgitation. Furthermore, 26 of the 27 patients with malfunctioning mechanical valves and 20 of the 24 patients with malfunctioning bioprostheses had abnormal findings using more than two techniques. In addition, each patient had at least one abnormal finding. In conclusion, malfunctioning mechanical or bioprosthetic prostheses could be detected using non-invasive techniques. The combined use of phonocardiography, M-mode and two-dimensional echocardiography and Doppler techniques is most helpful in detecting malfunctioning prostheses.

[Time analysis of mitral regurgitation in patients with mitral valve prolapse: a study by phonocardiography and Doppler techniques].

To assess the timing and duration of mitral regurgitation (MR) in patients with mitral valve prolapse (MVP), 20 subjects with mid-systolic click(s) and/or a late systolic murmur were studied using phonocardiography, two-dimensional echocardiography (2DE) and Doppler techniques including pulsed Doppler (PD), high pulse repetition frequency Doppler (HPRF), continuous wave Doppler (CW) and M-mode color Doppler (MD) methods and two-dimensional Doppler color flow mapping (2DD). The results were compared with those of 16 patients with a pansystolic murmur having late systolic accentuation. MVP with MR was observed in 15 of the 20 patients with mid-systolic clicks and/or a late systolic murmur and in all of the 16 patients with a pansystolic murmur. Using MD, MR signals were seen throughout systole and isovolumic relaxation period in all but one of these patients, and they were not related to the patterns of the systolic murmur. In only one, an MR signal was recorded just after the click. Five patients with a mid-systolic click lacked the findings of MVP, but two of them had MR signal only in early systole. Using PD and HPRF techniques, the timing and duration of MR signals in patients with mid-systolic clicks and/or a late systolic murmur were varied by changing the sites of the sample volume. Similarly, the timing and duration of MR signals in these patients were dependent on the ultrasonic beam direction by the CW method. In most patients with a pansystolic murmur having late systolic accentuation, however, MR signals throughout systole and the isovolumic relaxation period were demonstrated by each Doppler method. Therefore, PD, HPRF, and CW were not so efficiently sensitive or adequate techniques for investigating the timing and duration of MR, especially in patients with mid-systolic clicks and/or a late systolic murmur, who had mild or eccentric MR jets. In conclusion, 1) MR in MVP involves the entire systole and isovolumic relaxation period, 2) PD, HPRF and CW methods are not adequate for detecting mild or eccentric MR jets in patients with mid-systolic clicks and/or a late systolic murmur, and 3) MD is useful for the time analysis of MR in these patients.

[Ventricular free wall rupture following acute myocardial infarction: a two-dimensional echocardiographic assessment].

To assess the usefulness of two-dimensional echocardiography (2DE) in diagnosing ventricular free wall rupture following acute myocardial infarction, we studied the 2DE findings and the clinical pictures of seven consecutive patients with ventricular free wall rupture confirmed at the time of surgery or autopsy. Three patients had acute rupture; four, subacute rupture. All patients apparently had circulatory collapse despite continuing electrical activity at the onset of cardiac rupture. Four patients with subacute rupture recovered. In all patients, mild pericardial effusion was imaged by 2DE; however, this was not characteristic for cardiac rupture. In the patients with acute rupture, active left ventricular contractions were not observed after each QRS complex of the electrocardiogram. However, weak mitral valve motion was recorded at the time of cardiopulmonary resuscitation. The interesting and constant finding in acute rupture was the right ventricular collapse observed throughout the cardiac cycle. Diastolic right ventricular collapse was consistently observed in patients with subacute rupture, immediately after recovery from cardiogenic shock. Subacute cardiac rupture is a potentially curable lesion, and the clinical features and quick 2DE confirmation of cardiac tamponade allowed immediate surgery which saved two of the four patients.

[A new diagnostic criteria of mitral valve prolapse syndrome].

The diagnosis of mitral valve prolapse (MVP) should depend on the presence of significant mitral regurgitation or mitral complex abnormality as far as MVP is a diseased status. Concerning the echocardiographic diagnosis, the site of prolapse is difficult to determine correctly. In this study, Doppler color flow mapping was used to detect mitral regurgitation, and to decide the site of prolapse. Our new criteria of MVP include: (1) Phonocardiographic or auscultatory findings suggestive of mitral regurgitation or mitral complex abnormality. (2) A systolic bulging or an apparent systolic ballooning of the mitral valve by two-dimensional echocardiography. (3) A mitral regurgitant signal with an acceleration flow at the site of prolapse by Doppler color flow mapping.