Acute scrotal swelling in Henoch-Schönlein purpura: a case report.

Henoch-Schönlein purpura is a systemic vasculitis and sometimes presents as acute scrotal swelling in children. We report a case of Henoch-Schönlein purpura with acute scrotal swelling, which was correctly diagnosed based upon local physical findings. Scrotal ultrasonography showed normal testes and hydrocele testis around the affected testis 3 hours after the sudden onset of the pain. The scrotal symptoms improved in 2 days with steroid therapy. Scrotal ultrasonography was useful to diagnose Henoch-Schönlein purpura with scrotal involvement. Steroid treatment appeared to be effective for this condition.

[An infant of autoimmune hepatitis (type I) with cirrhosis].

A 6 year-old boy with autoimmune hepatitis accompanied with cirrhosis was reported. He was admitted to our hospital because of abdominal distention, high fever, and diarrhea. Laboratory examination revealed abnormalities in hepatic function, cholestasis, anemia, thrombocytopenia, hypoalbuminemia, hypocomplementemia, and low concentration of coagulation factors. Abdominal MRI, and asialoglycoprotein receptor-mediated liver scintigraphy strongly indicated liver cirrhosis. Viral hepatitis, Wilson's disease, and antitrypsin deficiency were excluded serologically. Instead, hypergammaglobulinemia, and positive antinuclear antibody suggested autoimmune hepatitis, and the survey of anti-mitochondrial antibody, anti-smooth muscle antibody, and anti-LKM-1 antibody was negative, indicating type I autoimmune hepatitis. Finally, the histology of liver biopsy specimen indicating the destruction of hepatic lobular architecture, dense mononuclear cell infiltrates, and severe fibrosis confirmed the diagnosis. He was treated firstly with methylprednisolone pulses, and then prednisolone p.o. + azathioprine p.o. All of the abnormal laboratory parameters improved to normal levels, indicating that the immunosuppressive therapy will be effective for the severe AIH with cirrhosis.

[A child of microscopic polyarteritis nodosa effectively treated with intravenous methylprednisolone pulses and serial cyclophosphamide pulse therapy].

Microscopic polyarteritis nodosa (mPAN) is a rare disorder in pediatric field of systemic small vessel vasculitis, and affects skin and musculoskeletal system accompanied by progressive necrotizing glomerulonephritis. We described here a 15-year-old boy with positive anti-neutrophil cytoplasmic antibody (MPO-ANCA) and severe mPAN, who was effectively treated with intravenous methylprednisolone pulse therapy followed by monthly cyclophosphamide pulses for 1 year. The histologic examination of renal biopsy specimen showed a severely desolated disease characterized by fibrinoid necrosis, crescent formation of most glomeruli and interstitial infiltration of inflammatory cells. The elevated titers of MPO-ANCA were useful markers for diagnosis, and the serial determinations of the antibody titers were indicative of disease activity. Moreover, dramatic clinical improvement after the induction of the combinatorial therapy and the disappearance of MPO-ANCA was correlated in the disease course. In this report, the serial determination of MPO-ANCA constituted a useful diagnostic tool and a sensitive marker of disease activity.

Nonhomologous recombination between the cytochrome b558 heavy chain gene (CYBB) and LINE-1 causes an X-linked chronic granulomatous disease.

We cloned and characterized a genomic DNA fragment including the deletion junction of a chronic granulomatous disease patient with a 25-kb deletion extending to the 5' two-thirds of CYBB. The 3' breakpoint of the deletion exists in exon 7 of CYBB. A LINE-1 element lies at 5 kb upstream of CYBB in normal persons, and the 5' breakpoint of the deletion in the patient is in the LINE-1 element. There are no significant homologies between corresponding normal 5' and 3' regions flanking the breakpoint of the patient, so a nonhomologous recombination is the most possible mechanism for this 25-kb deletion. The analysis also reveals that the patient has a novel 30-bp duplication in the 5' flanking region of the deletion point, which was transmitted by his mother with the deletion. Furthermore we suggest that the deletion occurred in his grandfather.

A 25-kb deletion in the 5' region of the cytochrome b558 heavy chain gene (CYBB) in a patient with X-linked chronic granulomatous disease.

We performed molecular genetic analyses of the family of a boy suffering from chronic granulomatous disease (CGD) after immunocytochemically confirming him and his mother to be an X-linked CGD patient and a mosaic carrier, respectively. Southern blot hybridization using cDNA for the cytochrome b558 heavy chain gene (CYBB) as a probe showed that the patient had a deletion in the 5' region of the CYBB and his phenotypically normal mother was heterozygous for this deletion. Polymerase chain reaction analyses of all 13 exons of the patient's CYBB gene demonstrated that the deletion extends from exon 7 or neighboring introns to 5' upstream. The length of the deletion was determined by pulsed-field gel electrophoresis and Southern blotting of genomic DNA using CYBB cDNA and the genetic marker pERT55-5, centromeric to CYBB, as probes. Both probes recognized common SfiI-NotI fragments of 120 kb and 95 kb in normal individuals and the patient, respectively. These results revealed that the patient has a 25-kb deletion spanning from the middle of CYBB to 5' upstream. This is the only report of a large 5' deletion in CYBB and also the first observation that CYBB and pERT55-5 are within 120 kb in Xp21.

Angiocentric immunoproliferative lesion associated with chronic active Epstein-Barr virus infection in an 11-year-old boy. Clonotopic proliferation of Epstein-Barr virus-bearing CD4+ T lymphocytes.

We report a pulmonary angiocentric immunoproliferative lesion (AIL) in an 11-year-old boy with chronic active Epstein-Barr virus (EBV) infection. The phenotypes of the proliferating lymphoid cells in the biopsied pulmonary lesion were CD2+, CD3+, CD4+, CD5+, CD7+, and HLA-DR+. EBV DNA was detected in the tumorous and the nontumorous tissue by Southern-blotting studies. Dual immunostains and combined immunohistochemistry/in situ hybridization showed the simultaneous presence of EBV-determined nuclear antigen or EBV-encoded small RNAs and T-cell markers in the lymphoid cells. Molecular genetic analysis of the tumorous lesion diagnosed as AIL grade III showed no clonal rearrangement of the T-cell receptor beta gene but a single type of fused terminal band of EBV. No such evidence of monoclonality was identified in the surrounding nontumorous tissue diagnosed as AIL grade I or II. The present case was a rare example of AIL in childhood and provides further histopathologic and molecular biological evidence supporting the concept of AIL as a continuous spectrum from premalignant lymphoproliferative disorders to monoclonal, overt malignant lymphoma.

Evaluation of biventricular interaction in various cardiac diseases by pulsed Doppler echocardiography.

We evaluated the biventricular interaction in various cardiac diseases by pulsed Doppler echocardiography. A/R (atrial peak filling velocity/rapid peak filling velocity) from inflow wave and PEP/ET (pre-ejection period/ejection time) from outflow wave were measured as parameters of both ventricular function. In 20 normal cases, A/R and PEP/ET correlated well between the right and left ventricles, respectively. In 6 cases with pulmonary hypertension, both values of A/R and PEP/ET were higher than those in normal cases in the right ventricle, but not in the left ventricle. In 15 cases with left ventricular infarction, these values were higher than those in normal cases. Not only in the left ventricle but also in the right ventricle, and good correlation between both ventricles was observed in each parameter. In 15 cases with hypertrophic nonobstructive cardiomyopathy and 15 cases with dilated cardiomyopathy, both values of A/R and PEP/ET in the both ventricles were also higher than those in normal cases, respectively, however, both parameters did not correlate with the both ventricles. It is suggested that the right ventricular function is influenced not only by the afterload or interventricular septal function, but also by the myocardial property of the right ventricle itself, in cases with cardiomyopathies.

Effects of long-term beta-blockade (metoprolol) therapy in patients with dilated cardiomyopathy.

Twenty-two patients with dilated cardiomyopathy (DCM) were treated with metoprolol and their clinical courses were compared with those of 26 patients untreated with beta-blocking agents (non beta group). Of the 22 patients treated with metoprolol, 19 (beta group) were treated for a long period, 3 patients left the study within its first 6 months. Using the NYHA classification, 4 patients of the beta group were evaluated as having clinically improved, while none was aggravated, excluding 2 cases of death which occurred during the follow up period. In the non-beta group, clinical improvement was found for 2 patients and aggravation in functional class for 10. The left ventricular diameter was significantly decreased and parameters of systolic function and exercise tolerance were significantly improved in patients of the beta group, while no such improvements occurred in patients of the non-beta group. Twenty-four-hour ECG monitoring demonstrated a significant reduction in incidences of ventricular extrasystole in the beta group but not in those of the non-beta group. Improvement of arrhythmias, evaluated using Lown's grading system, was also identified more frequently in the beta group than in the non-beta group. During the follow-up period, 2 patients of the beta group and 10 patients of the non-beta group died. The survival curve for patients of the beta group prepared using the Caplan Meier Method was better than that for patients of the non-beta group. Metoprolol was therefore found to be useful for treatment of DCM.

[A case of hypogammaglobulinemia associated with polyarteritis nodosa presenting a variety of symptoms in childhood].

A case of polyarteritis nodosa (PN) in childhood involving various organs such as the gastrointestinal tract, skin, CNS, kidneys and liver with hypogammaglobulinemia is reported. This 6 month old girl was admitted to our hospital with vomiting, diarrhea, bloody stools with mucous and weight loss. For the past 5 months she had these abdominal symptoms. She was diagnosed as having PN of the Kussmaul-Maier variety on the grounds of the biopsy of skin lesion where a necrotizing vasculitis was found. Prednisolone and methylprednisolone pulse treatment were not effective in suppressing the progress of the disease. At the age of 1 year 7 month a combination therapy of prednisolone and immunosuppressants (cyclophosphamide) was started and this was found to be effective. She was discharged when she was 2 year and 2 month. The dosage of prednisolone was tapered as the activity of the PN decreased and she did well with a maintainance dosage of 9.5 mg/day. At 3 year 6 month of age she suddenly developed hypertension (the plasma renin activity was found to be 16.6 ng/m/hr. and the aldosterone 220 ng/dl). CNS involvement such as spinal cord dysfunction, left sided convulsions, cerebral hemorrhage developed 5 months later. Methylprednisolone pulse therapy was performed 3 times and 2 mg/kg/day of prednisolone was administered. In spite of this therapy she passed away with a massive cerebral hemorrhage at the age of 4 year 8 month. Unfortunately an autopsy was not performed. Results of the immunological tests proved that the hypogammaglobulinemia was a common variable immunodeficiency (CVI). It has been reported that primary immuno-deficiency syndrome is often associated with collagen disease and auto-immune disease. This lack of the defense mechanism against the virus or extra antigen could be related to the onset of collagen and auto-immune disease. As the correlation between CVI and PN has not been clarified this case is of interest as concerns the cause of PN.

Clinical and histopathologic correlation in patients with dilated cardiomyopathy. Value of force-velocity product.

To evaluate the relation between cardiac function and myocardial damage in patients with dilated cardiomyopathy (DCM), we compared echocardiographic parameters and histopathologic findings of the biopsied myocardium in 50 cases with DCM. As wall motion is much influenced by the increased afterload in cases with large ventricles, we generated a new contractile parameter, Force-Velocity Product (FVP). FVP was defined as the result obtained by multiplying mean circumferential fiber shortening velocity by noninvasive end-systolic wall stress. FVP correlated with percent fibrosis in the myocardium, which was reflected by no other echocardiographic parameter. We also evaluated the prognostic values of the echocardiographic and histopathologic parameters. FVP had the highest value among them. We conclude that FVP is a very useful clinical parameter, with the further advantage of being obtained noninvasively.

[Genesis of systolic anterior motion (SAM) of the mitral valve in patients with aortic regurgitation].

This study was performed to evaluate the incidence and genesis of systolic anterior motion (SAM) of the mitral valve apparatus in patients with aortic regurgitation (AR). The study population consisted of 44 patients with non-rheumatic AR, without significant aortic stenosis or mitral regurgitation. The presence and location of SAM in the short-axis view were determined by M-mode echocardiography guided by two-dimensional echocardiography. The extent and direction of the regurgitant jet were decided by pulsed or two-dimensional Doppler echocardiography. SAM was observed in 21 (48%) of the 44 patients, and it was more frequently observed in patients with an etiology of aortic valve prolapse or annuloaortic ectasia than in those of other etiology (10/14 vs 10/30; p less than 0.05). Twenty-eight patients whose regurgitant jet was directed posteriorly and impinged on the mitral valve apparatus had a significantly higher incidence of SAM than did the other 16 patients (18/28 vs 3/16; p less than 0.01). In eight of 10 patients in whom the direction of the regurgitant jet could be precisely observed by two-dimensional Doppler echocardiography. SAM was observed at the place where a regurgitant jet was directed along the anterior mitral valve in the short-axis view. M-mode measurements (LVDd, LVDs, %FS, LVDd-LVDs) of the patients with SAM had greater values than those of patients without SAM.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of afterload in progression of dilated cardiomyopathy--evaluation with force-velocity relation.

To evaluate the clinical role of afterload in progression of dilated cardiomyopathy (DCM), a loading examination (study 1) and a follow-up study (study 2) were carried out, using echocardiography, and analysed with Force-Velocity relation (FVR). FVR was defined as the relation between end-systolic wall stress (WSes) and mean circumferential fiber shortening velocity (mVcf). In study 1, the cardiac responses to angiotensin II loading in 30 cases with DCM (17 cases with presumed causes, and 13 without) were observed. These cardiac responses could be described by a hyperbola (Y = 197/(X + 9) + 0.04, r = 0.63) on the graph of FVR, and each response also seemed to fit the hyperbola (Y = a/(X + 9) + 0.04). This "a" value differed according to the presumed causes, and had an inverse correlation with % fibrosis in the biopsied cardiac muscle (Y = 0.86 + 29.9, r = -0.64, p less than 0.02). In study 2, during a mean clinical course of 3.7 years, the cardiac function (mVcf) in 19 out of 25 cases with DCM changed inversely with the changes of WSes on FVR. The "a" value calculated by the same method as study 1 did not differ before and after the follow-up. It did, however, vary according to the clinical outcome. These results suggest that afterload plays an important role in progression of DCM, and that an evaluation of cardiac function employing FVR may be helpful for assessing the myocardial damage, causative factors, and the prognosis of DCM.

[Observations of dilated cardiomyopathy with marked clinical improvement].

Although the prognosis of dilated cardiomyopathy (DCM) is poor, some patients occasionally follow favorable clinical courses and have significant improvement in cardiac function. To elucidate the mechanism of such improvement, we compared the clinical and pathological findings of 54 cases with DCM, including 12 cases with significant improvement (Dd less than 55 mm, %FS greater than 22%) during two years' follow-up (improved group), 26 without significant improvement (unimproved group), and 16 who died within two years (decreased group). Percent fractional shortening (%FS) in the deceased group was less than that in the unimproved group (12.4 +/- 3.9 vs 17.2 +/- 6.2, p less than 0.01). Pulmonary capillary pressure (PC) and % fibrosis in the deceased group were greater than those in the unimproved group [(22.7 +/- 9.5 vs 11.4 +/- 4.2 mmHg, p less than 0.001), (21.7 +/- 9.9 vs 13.4 +/- 3.6, p less than 0.01)], respectively. Although Dd, Ds, %FS, end-diastolic wall thickness (Thd), and PC in the improved group were not different from those in the unimproved group. End-systolic wall stress (WSes) in the improved group was greater than that in the unimproved group (376 +/- 73 vs 319 +/- 60 g/cm2, p less than 0.02), but % fibrosis was less in the improved group (7.6 +/- 3.4 vs 13.4 +/- 3.6, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Comparison of regional contractile dynamics and pathological findings of the left ventricular wall in patients with hypertrophic cardiomyopathy].

To investigate the relationship between regional contractile dynamics and regional myocardial lesions of the left ventricular wall in patients with hypertrophic cardiomyopathy (HCM), autopsy findings of 11 patients were compared with their ante mortem echocardiographic findings. The regional systolic wall thickenings (%RWT) of the interventricular septum (IVS) and left ventricular posterior wall (LVPW) obtained using M-mode echocardiography were converted into % normalized RWT (%NRWT) by the averaged %RWT in 15 normal subjects. The %NRWT was compared with the wall thickness obtained by echocardiography and/or autopsy, and histological findings, such as the myocardial fibrosis ratio, disarray area ratio, and mean myocyte diameter. 1. There were no significant correlations among wall thickness of the left ventricle, the myocardial fibrosis ratio, the disarray area ratio, and the mean myocyte diameter of each segment. 2. The %NRWT in 22 segments of the 11 patients with HCM was not significantly related to the echocardiographic wall thickness at end-systole, the autopsy wall thickness, the mean myocyte diameter and the disarray area ratio, but that correlated significantly with the echocardiographically-determined wall thickness at end-diastole (r = -0.53, p less than 0.02), and with the myocardial fibrosis ratios (r = -0.59, p less than 0.005). 3. The %NRWT in the IVS was significantly less than that in the LVPW. The %NRWT in all segments of the LVPW was significantly related to the myocardial fibrosis ratios (r = -0.80, p less than 0.005), but was not related to the wall thicknesses or the disarray area ratios.(ABSTRACT TRUNCATED AT 250 WORDS)

[Prognosis of hypertrophic cardiomyopathy: echocardiographic and postmortem histopathologic study of 30 patients].

To clarify the influence of cardiac function of myocardial histologic lesions on the prognosis of hypertrophic cardiomyopathy (HCM), most recent echocardiographic findings of 30 deceased patients were reviewed. In 12 patients, histological sections from the left ventricular transverse plane made at necropsy were examined. According to the main causes of death, patients were categorized into four groups as sudden death (17 cases), heart failure death (four cases), embolic death (four cases), and non-cardiac death (five cases). 1. Clinically, atrial fibrillation and heart failure (NYHA III, IV) were frequently observed in heart failure and embolic groups. 2. Echocardiographically, left ventricular wall thickness did not differ among the four groups, but percent fractional shortening was significantly smaller in heart failure group than in non-cardiac group, and left ventricular end-diastolic dimension (LVDd) and left atrial dimension were significantly greater in heart failure group than in non-cardiac group. The normalized rapid filling rate was less in heart failure, embolic, sudden death and non-cardiac groups in that order. 3. Histopathologically, the mean myocyte diameter (MD) and percent area of disarray (%D) did not differ among the four groups, but % area of massive fibrosis (MF) greater than 2 mm2 was larger in heart failure, embolic, sudden death and non-cardiac groups in that order, especially in heart failure group. 4. Comparison of echocardiographic and histopathological findings: Though MD and %D did not correlate with any echocardiographic indices, %MF correlated significantly with LVDd (r = 0.83, p less than 0.005), and correlated inversely with the normalized rapid filling rate (r = -0.80, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

[A trial diagnosis of latent dilated cardiomyopathy].

To diagnose latent dilated cardiomyopathy (latent DCM), we performed loading echocardiography with Angiotensin II and ergometer exercise in 41 patients. Twenty-one patients were suspected of having latent DCM because of histories, of heart failure of myocarditis; 10 patients had DCM; and 10 normal persons served as controls. On angiotensin II loading, cardiac function deteriorated in the DCM group, but it was maintained in the normal controls. Nine patients in the latent DCM group showed the same pattern as normals (L1-group), and 12 did as the DCM group (L2-group). Although % fractional shortening, end-diastolic and end-systolic dimensions of the left ventricle did not differ between the L1 and L2-groups, the A/R, the ratio of the pulsed Doppler echocardiogram at the left ventricular inflow tract, was larger and the exercise change of the % fractional shortening and exercise tolerance were less in the L2-group than in the L1-group. Furthermore, the biopsy findings of the L2-group were similar to those of the DCM group in terms of myocardial degeneration, myocardial hypertrophy and interstitial fibrosis. Thus, patients in the L2-group were thought to have a risk for DCM, and were cases of latent DCM. Angiotensin II loading is thought to be useful for diagnosing such cases.