Subacute sarcoid myositis with ocular muscle involvement; a case report and review of the literature.

Sarcoidosis is a chronic granulomatous disease that can affect multiple organs. The lungs, eyes, and skin are known to be highly affected organs in sarcoidosis. There have been reports based on random muscle biopsy that 32-80% of systemic sarcoidosis comprises noncaseating granulomas; however, muscle involvement in sarcoidosis is generally asymptomatic and has an unknown frequency. We describe a case of acute to subacute sarcoid myositis of the skeletal and extraocular muscles. Typical ophthalmic involvement (manifested by infiltration of the ocular adnexa, intraocular inflammation, or infiltration of the retrobulbar visual pathways) and extraocular sarcoid myositis (as with the present case) is infrequently reported. It is important to keep in mind the rare yet perhaps underestimated entity of sarcoid myositis, and to utilize muscle biopsy and imaging tests for appropriate diagnosis and management of patients with sarcoidosis.

Stimulation of interleukin-1 beta production may be involved in unresponsiveness to erythropoietin therapy.

Recombinant human erythropoietin (rHuEPO) can dramatically improve anemia in dialysis patients, but about 20% of patients show a poor response to this agent. It has been reported that cytokines, including interleukin (IL)-1 beta, may inhibit the maturation of erythrocytes. To investigate the mechanisms of unresponsiveness to rHuEPO, we isolated peripheral blood mononuclear cells from 12 patients on continuous ambulatory peritoneal dialysis who were receiving maintenance rHuEPO therapy for renal anemia. Cells were cultured with rHuEPO and IL-1 beta production was assessed. In the six patients who did not respond to rHuEPO therapy, there was a marked increase in IL-1 beta during culture with rHuEPO. In contrast, the addition of rHuEPO to cultures of cells from the six responding patients caused little increase in IL-1 beta, and there was a significant difference between the two groups. Induction of IL-1 beta by rHuEPO may be one cause of persistent anemia in dialysis patients.

Investigation of the influenza-like symptoms associated with recombinant human erythropoietin therapy.

The mechanism by which fever and influenza-like symptoms occur, after the administration of recombinant human erythropoietin (rHuEPO) to patients on continuous ambulatory peritoneal dialysis, was investigated. Peripheral blood mononuclear cells, obtained from two patients with fever and/or influenza-like symptoms related to the administration of rHuEPO for the treatment of anaemia were cultured with or without rHuEPO (100, 200, and 300 U/ml). Production of interleukin-1 beta and tumour necrosis factor-alpha was higher in cultures with rHuEPO than in cultures without rHuEPO, although the dose relationships were not clear. These findings suggest that increased production of interleukin-1 beta and tumour necrosis factor-alpha 1, induced by administration of rHuEPO, may cause fever and influenza-like symptoms.

Dose escalation induces tolerance to side-effects of erythropoietin in a patient with dialysis anaemia: case report.

A 51-year-old woman began haemodialysis for chronic renal failure in February 1981. Symptomatic anaemia required treatment with recombinant human erythropoietin (rHuEPO) in February 1990 (3000 IU, twice weekly, intravenously). She developed influenza-like symptoms and treatment was withdrawn. In June 1994 rHuEPO was resumed at a very low dose of 100 IU subcutaneously three times weekly, and was increased gradually to 500 IU, without inducing any side-effects. At this dose the haematocrit was maintained at 22.0-25.0% and the symptoms of anaemia improved. In patients like ours, with influenza-like symptoms caused by rHuEPO therapy, dose escalation starting from an ultra-low dose may be effective in avoiding side-effects.

Electrophysiological delineation of the specialized conduction system during cardiotomy and its clinical appraisal.

The specialized conduction system was delineated electrophysiologically during cardiotomy, primarily to discover the topographic relations between the conduction system and the intracardiac structures. A series of 72 cases operated on for congenital cardiac anomalies was studied. A superficial location of the His bundle along the lower rim of the defect was often noticed in cases of large ventricular septal defect (VSD) of type II or III, whereas a marked leftward deviation was noted, in cases of tetralogy of Fallot (TOF). Significant deflections were commonly recorded on the tricuspid annulus a few mm below the defect, and frequently on the lower rim behind the muscle of Lancisi (ML) in both VSD and TOF (left ventricule side in TOF). Particular care should be taken in these areas, during closure of any defect. The ML was found to be a rough landmark for the right bundle branch, although topographic relations were slightly altered according to the type of disease. The change may also depend on whether the perimembranous defect is of the inlet- or outlet-type.

Renal osteodystrophy in hemodialysis patients.

Patterns of bone loss in the axial and appendicular skeleton were studied in 88 chronic hemodialysis patients (59 males and 29 females) and 60 normal volunteers (30 males and 30 females). The hemodialysis patients were properly medicated with phosphate binders and 1 alpha-OH D3 where necessary. The metacarpal index (MCI), sigma gray scale/diameter (sigma GS/D) and bone mineral content (BMC) were measured as bone mass indices, and the relationship investigated between clinical factors [age, duration of hemodialysis, serum phosphate (P), calcium (Ca), carboxy-terminal fragments of parathyroid hormone (C-PTH), osteocalcin (OC), alkaline phosphate (ALP) and Ca x P]. The bone loss in the hemodialysis patients was greater than that in the normal controls and was accelerated after menopause in women. However, the bone mass indices in a few of the hemodialysis patients of advanced age (over 60) showed higher values than those of the controls. The bone mass indices in male hemodialysis patients showed a negative correlation with the hemodialysis duration, C-PTH and OC, as did those in female patients with hemodialysis duration. On the other hand, BMC in female hemodialysis patients showed a negative correlation with P, C-PTH and Ca x P. In conclusion, age and the duration of hemodialysis are the most essential factors in skeletal and trabecular bone loss in male and female hemodialysis patients. Subsequent factors responsible for skeletal bone loss in male patients are C-PTH and OC, and those for trabecular bone loss in female patients are P, C-PTH and Ca x P. Control of the levels of C-PTH, OC, P and Ca x P is recommended for prevention of bone loss in hemodialysis patients.

Serum soluble interleukin 2 receptor in patients with IgA nephropathy.

Serum soluble interleukin 2 receptor (IL-2 R) was determined by the ELISA method in 29 cases of IgA nephropathy and 50 healthy controls. The results showed that the value in IgA nephropathy cases was significantly higher than that in healthy controls. Furthermore, among the cases of IgA nephropathy, the value was significantly higher in the groups with hypertension, elevated serum IgA and depressed creatinine clearance than in that of the corresponding controls. These findings suggest that serum soluble IL-2 R can serve as a prognostic index of IgA nephropathy.

An immunohistochemical study of extracellular matrix components and integrins in human glomerular diseases.

The localization of extracellular matrix components and their cell surface receptors (integrins) was studied in 130 subjects in order to clarify their participation in the progression and aggravation of various types of nephritis. Included in the study were 2 normal subjects, 14 patients with minimal change disease, 2 patients with minimal change nephrotic syndrome, 65 patients with IgA nephropathy, 18 patients with mesangial proliferative glomerulonephritis, 15 patients with membranous glomerulonephritis, 5 patients with membranoproliferative glomerulonephritis and 9 patients with systemic lupus erythematosus (SLE). The distribution of fibronectin (FN), vitronectin (VN), laminin (LN), heparan sulfate proteoglycan (HSPG), type III, IV, V, VI collagen, fibronectin receptor (FNR) and vitronectin receptor (VNR) in the glomerulus was studied employing the indirect immunoperoxidase method. FN, LN, type IV, V and VI collagen, FNR and VNR were found to be distributed in the expanded mesangial region in IgA nephropathy, mesangial proliferative glomerulonephritis and membranoproliferative glomerulonephritis. Deposition of VN was observed in some of the patients. In membranous glomerulonephritis and membranoproliferative glomerulonephritis, the distribution of FN, LN, type IV collagen, FNR and VNR was increased in the thickened loop wall and VN deposition was also observed. Quantitative and functional changes in the extracellular matrix and integrins, therefore, appear to participate in the progression and aggravation of glomerulonephritis.

In vitro immunoglobulin production by peripheral blood mononuclear cells as a prognostic factor in IgA nephropathy.

To determine whether immune system disorders are involved in the exacerbation of IgA nephropathy, the immunoglobulin production of peripheral blood mononuclear cells obtained from 45 IgA nephropathy patients was measured and then compared with that of healthy individuals. The level of IgA production was classified into an elevated group and a non-elevated group and comparisons were made with various clinical factors considered to be related to exacerbation of this disease. The results indicated that although there was no significant difference in immunoglobulin production of the peripheral mononuclear cells between IgA nephropathy cases and healthy individuals in the group not stimulated with pokeweed mitogen (PWM), the group stimulated with PWM revealed a production of IgA, IgG, and IgM which was significantly elevated (P less than 0.01). Also, within the group stimulated with PWM, hypertension, severe proteinuria and microscopic hematuria, elevated BUN and serum creatinine values, decreased 15-min PSP and creatinine clearance values, severe histological damage, and severe IgA deposition were observed more in the elevated IgA production group than in the non-elevated group. These findings suggest that an elevated IgA production plays an important role in the excerbation of this disease.

[Clinical analysis of intrapulmonary lymph nodes].

We encountered 12 cases (9 men, 3 women) of intrapulmonary lymph nodes, discovered by chest radiography or chest CT and identified by thoracoscopic lung biopsy (in 10 cases), open lung biopsy (1 case) or lobectomy (1 case). We also studied the literature related to intrapulmonary lymph nodes in Japanese. Many intrapulmonary lymph nodes were found in the lower lung field, few in the upper lung field. All intrapulmonary lymph nodes were spherical and were located under the pleura, but we were not able in some cases to differentiate them from malignancies by the CT scanfindings. We could not diagnose them or rule out malignancy before surgery. Pathological findings revealed that all of them showed anthracosis. Silicotic changes were found in three cases. We consider that thoracoscopy is useful in making a definite diagnosis if peripheral pulmonary lesions cannot be diagnosed. We emphasize that intrapulmonary lymph nodes should be taken into consideration in differential diagnoses of small nodular lesions in the lung.

[Induction chemotherapy (cisplatin + vinorelbine) is found to be markedly effective for squamous cell lung carcinoma with sarcoidosis--a case report].

A sixty-one-year-old man was admitted to our hospital because of a right lung tumor shadow. He had been diagnosed as having sarcoidosis at the age of fifty-seven. He was newly diagnosed as having squamous cell carcinoma by trans bronchial biopsy. He was treated with an induction chemotherapy (cisplatin 80 mg/m2 + vinorelbine 20 mg/m2) followed by right middle and lower lobectomy with a mediastinal nodal dissection, because the stage of his carcinoma was cT2N2M0. Resected lung tissue showed the disappearance of cancer cells. Dissected mediastinal and hilar lymph nodes showed many sarcoid granulomas. Cisplatin combined with vinorelbine might be an effective chemotherapy for non-small cell lung carcinoma.

Electrophysiological delineation of the specialized conduction system under cardiotomy and its clinical role.

Electrophysiological delineation of the specialized conduction system was performed under cardiotomy on 64 patients: 51 with ventricular septal defect (VSD), 11 with tetralogy of Fallot (TOF) and 2 with transposition of the great arteries (TGA, III). Some histological study was done for confirmation. In large VSD of type II or III, superficial location of the His bundle was shown by a tall H deflection recorded along the inferior rim, coinciding with a high incidence of conduction disturbance in this malformation. One characteristic in TOF was a deflection recorded along the posteroinferior rim rather exclusively on the left ventricular side, coinciding with the anatomic course of the His bundle. A deflection was frequently recorded at an area a few mm posterior to the muscle of Lancisi (ML) or the Lancisi equivalent structure (LES); it was relatively common in ordinary types of VSD, and presumed as the penetrating site of the right bundle branch (RBB) and/or near the bifurcated portion of the His bundle. The second portion of the RBB was not clearly delineated in general, particularly in TOF, but always found within the septomarginal trabecle when delineated. Our conclusion, together with histological study, was that one may use the ML or the LES as a rough marking for the course of the RBB. By this recognition, the surgically induced complete right bundle branch block has been diminished significantly. Variation of the course of conduction system as well as limits of this diagnostic measure are described herein.

Stimulation of tumour necrosis factor-alpha production by recombinant human erythropoietin may contribute to failure of therapy.

Although the mechanism of unresponsiveness to recombinant human erythropoietin therapy in dialysis patients has been studied extensively in recent years, many aspects remain unclear. We previously found that administration of erythropoietin induces interleukin-1beta, a cytokine that inhibits erythropoiesis. The present study investigated the involvement of tumour necrosis factor-alpha, another cytokine which inhibits erythropoiesis. Peripheral blood mononuclear cells were obtained from 18 patients on continuous ambulatory peritoneal dialysis, who were being treated with erythropoietin for renal anaemia, and were cultured with various concentrations of erythropoietin (0, 1, 5, 10, and 50 U/ml). Then the tumour necrosis factor-alpha level in the culture supernatant was assayed. The 18 patients were divided into four groups on the basis of the haematocrit after treatment: group A (n = 3), <23.0%; group B (n = 5), 23.0-24.9%; group C (n = 7), 25.0-26.9%; and group D (n = 3), > or =27.0%. In group A, the tumour necrosis factor-alpha level in the culture supernatant was increased by incubation with erythropoietin, while it was not increased in other groups. The tumour necrosis factor-alpha level was significantly higher in group A than in the other groups at erythropoietin concentrations of 5 U/ml. These results suggested that induction of tumour necrosis factor-alpha is one of the reasons for unresponsiveness to recombinant human erythropoietin.

Mechanism of increased serum soluble interleukin-2 receptor levels in patients on continuous ambulatory peritoneal dialysis.

OBJECTIVE: The aim of this study was to investigate the mechanism underlying the increase of serum soluble interleukin-2 receptor (IL-2R) levels in patients on continuous ambulatory peritoneal dialysis. MATERIAL AND METHODS: In 13 dialysis patients and 17 healthy controls, serum soluble IL-2R levels were determined by enzyme-linked immunosorbent assay, and CD25-positive (cell surface IL-2R-positive) cells were detected by flow cytometry. Soluble IL-2R levels were also measured in the supernatant of cultured peripheral blood mononuclear cells. RESULTS: The serum soluble IL-2R level was significantly higher in the patients than in the healthy controls (p < 0.0001). In contrast, both the percentage and the absolute count of CD25-positive cells showed no significant differences, and neither did the soluble IL-2R level in culture supernatant. Serum soluble IL-2R levels showed a positive correlation with the serum beta2-microglobulin level (p < 0.01), the age of the patients (p < 0.05), and duration of dialysis (p < 0.05), as well as a negative correlation with the urine volume (p < 0.05). CONCLUSIONS: The increase of serum soluble IL-2R in patients on peritoneal dialysis may be caused by accumulation due to its low transperitoneal clearance and low urinary excretion.

Clinical appraisal of his bundle electrocardiogram taken under cardiotomy in congenital heart disease.

The specialized conduction system in the heart was electrophysiologically delineated under cardiotomy in 74 patients with congenital heart disease primarily to determine the topographic relationship of the conduction system to intracardiac structures. Histological study was also done to evaluate the electrophysiological data. Differences were found between the ordinary ventricular septal defect (VSD), inlet-type perimembranous defect, and the ordinary tetralogy of Fallot (TOF), outlet-type perimembranous defect. A superficial run of the His bundle along the lower rim summit of defect was often demonstrated electrophysiologically in large VSD of types II or III, whereas the bundle took marked leftward course in TOF. The right bundle branch (RBB) ran beneath or slightly posterior to the Lancisi equivalent structure (LES) in VSD, while it ran under or slightly anterior to LES in TOF. This papillary muscle could be a rough landmark of the RBB. The course of the RBB in TOF, however, had to be histologically confirmed, since its deep location made electrophysiological delineation difficult. All the sites with a high deflection were the areas where the conduction system was histologically demonstrated beneath the endocardium.

Serum soluble interleukin-2 receptor in patients with glomerulonephritis.

Serum soluble interleukin-2 receptor (IL-2R) concentrations were determined using the ELISA method in 55 cases of glomerulonephritis. These patients can be classified as 29 cases of IgA nephropathy, 10 cases of membranous glomerulonephritis and 16 cases of mesangial proliferative glomerulonephritis. Our results showed that serum soluble IL-2R concentrations in glomerulonephritis cases were significantly higher than those in healthy controls. Among the different types of glomerulonephritis cases, however, no significant differences in serum soluble IL-2R were observed. While we found a significant positive correlation of serum soluble IL-2R to BUN and creatinine, we also found a significant negative correlation between serum soluble IL-2R and creatinine clearance. These findings suggest that serum soluble IL-2R can serve as an indicator of exacerbation of glomerulonephritis.