Clinical,Biochemical, and Pathological Features in a Patient with Plasma Cell Dyscrasia and Fanconi Syndrome

Multiple myeloma is associated with a wide array of renal diseases that include myeloma cast nephropathy, monoclonal immunoglobulin deposition disease, amyloidosis, cryoglobulinemia, tubular dysfunction, pyelonephritis, nephrocalcinosis, urate nephropathy, and infiltration by atypical plasma cells (or myeloma cells). Filtered immunoglobulin light chains may affect both the distal and, more frequently, the proximal tubule. Tubular abnormalities in patients with plasma cell dyscrasia may be more frequent than previously thought. A patient with a plasma cell dyscrasia is described, who presented with biochemical features consistent with Fanconi syndrome. Immunoelectron microscopy performed on the renal biopsy confirmed the presence of kappa light chain immunoglobulin in intracytoplasmic crystals in proximal tubular epithelial cells. This report is one of a few demonstrating the presence of light-chain immunoglobulin in intratubular crystals in a human renal biopsy obtained from a patient with a plasma cell dyscrasia and Fanconi syndrome.     

Treatment of chronic hepatitis C in a patient with Fanconi anaemia

Fanconi anaemia is a rare autosomal recessive disorder with progressive bone marrow failure and predisposition to malignancy. We report a case of a 26-year-old female patient with Fanconi anaemia and severe chronic active hepatitis C virus infection. Her past medical history included treatment with multiple blood transfusions and bone marrow transplantation at the age of 13. The decision to treat the infection was taken, and history of hematologic disease contributed to the introduction of therapy with leukocyte interferon-α n3 and ribavirin combined with a granulocyte - colony stimulating factor. The treatment was well tolerated and after 48 weeks a reduction of the viral load and alanine aminotransferase activity were achieved. No adverse effects on bone marrow functioning were noted.     

A case of reactive plasmacytosis mimicking multiple myeloma in a patient with primary Sjogren's syndrome

Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease with well-documented association of lymphoid malignancies during the progress of the disease. Although several types of malignancy and pseudomalignancy have been reported in pSS, low-grade non-Hodgkin's lymphomas are the most frequently observed. Reactive plasmacytosis mimicking myeloma is a very rare condition in association with pSS. We describe a 72-yr-old woman with pSS who presented with hypergammaglobulinemia, and extensive bone marrow and lymph node plasmacytosis, which mimicked multiple myeloma. In this patient, there was an abnormal differentiation of memory B cells to plasma cells in the peripheral blood suggesting underlying pathogenetic mechanism for this condition.     

Granulocyte-colony stimulating factor concentrations in a patient with plasma cell dyscrasia and clinical features of chronic neutrophilic leukaemia.

In order to study the pathogenesis of plasma cell dyscrasias with associated clinical features of chronic neutrophilic leukaemia, the concentration of granulocyte-colony stimulating factor (G-CSF) was measured in a patient, a 73 year old man, who underwent steroid pulse therapy. High G-CSF concentrations and leucocyte counts prior to treatment declined rapidly on administration of dexamethazone, but rose subsequently. G-CSF was not detected in primary cultures of bone marrow cells, but large amounts of interleukin-6 were found in the culture supernatant. These observations suggest that the neutrophilia observed in the patient represented a reactive response to G-CSF secreted from abnormal plasma cells or stromal cells rather than the existence of a genuine myeloproliferative disorder.     

Clinical, pathological, and biochemical studies in a patient with propionic acidemia and fatal cardiomyopathy

A patient diagnosed at 9 months with a milder form of propionic acidemia was functioning at a near normal intellectual level and a normal neurological level at age 8. After 2-week history of feeling "poorly" but functioning normally, she became acutely ill and succumbed to heart failure and ventricular fibrillation in 12 h. At post-mortem the heart was hypertrophied and had low carnitine levels, despite carnitine supplementation and repeatedly normal plasma carnitine levels. The findings in this patient provide a possible mechanism for the cardiac complications that are becoming more apparent in propionic acidemia.     

大鼠老年多器官功能障碍综合征生理、生化及超微结构的变化

目的:研究老年多器官功能障碍综合征(MODSE)动物模型超微结构的改变特点与生理、生化指标变化,探讨老年多器官功能障碍发生机制,提供防治老年多器官功能障碍综合征的依据。方法:建立盲肠结扎穿孔术(CLP)的MODSE组、青年多器官功能障碍综合征(MODSY)组及相应的假手术对照组。在术后24h采用透射电镜技术观察重要器官(心、脑、肺、肝和肾)的超微结构变化,同时检测各组大鼠的呼吸频率(RR)、心率(HR)和血压(BP)、血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TB)、肌酐(Cr)、尿素氮(BUN)等生理、生化指标水平的改变。结果:观察MODSE组和MODSY组的重要器官组织超微结构时发现,术后24h两组实验大鼠的重要器官及其血管内皮细胞的超微结构均有不同程度的损伤;除RR、BP、HR指标外,其他5项生化指标较假手术对照组亦有显著差异(P＜0.05)。结论:不同程度的重要器官组织的细胞损伤(其中以MODSE实验组的细胞损伤最为严重)与相应的生理、生化指标改变的一致性,说明血管内皮细胞的损伤可不同程度导致微循环障碍,引起相应组织的供血不足,进而使细胞的代谢功能受到影响,发生细胞变性、坏死。在纠正器官功能不全的同时,尤应注意积极采取保护血管内皮细胞的治疗措施。     

Newly developed multiple myeloma in a patient with primary T-cell lymphoma of bone

Primary non-Hodgkin's lymphoma of bone (PLB) is rare, and generally presents as a single extensive and destructive bone lesion. Histopathologically, most cases present as diffuse large B-cell lymphoma, and T-cell lymphoma is rare. By contrast, multiple myeloma is a disease defined as the neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin. We report a case of multiple myeloma that developed during treatment of PLB in a type of T-cell. A 48-yr-old man was diagnosed as T-cell PLB, stage IE, 18 months ago. The patient received the chemoradiotherapy and salvage chemotherapy for PLB. However, the lymphoma progressed with generalized bone pain, and laboratory findings showed bicytopenia and acute renal failure. On bone marrow biopsy, the patient was diagnosed as having multiple myeloma newly developed with primary T-cell lymphoma of bone. In spite of chemotherapy, the patient died of renal failure.     

Clinical, ultrastructural and biochemical studies in two sibs with Ehlers-Danlos syndrome type VI-B-like features

Two Turkish sibs with clinical features of Ehlers-Danlos syndrome type VI-B are presented. The hydroxylysine contents of dermis and gel electrophoresis of type I and type III collagen produced by fibroblasts were normal. Ultrastructural studies of skin collagen and elastic fibers showed discrete abnormalities. Other syndromes with similar clinical, biochemical and ultrastructural features are discussed.     

Clinical and molecular features of Ewing sarcoma in a patient with triple-X syndrome.

A case of Ewing sarcoma in a 16-year-old girl with 47 XXXc karyotype is reported.     

Intestinal microvillous atrophy in a patient with Down syndrome and aganglionic megacolon

Intestinal microvillous disorders are an uncommon cause of severe diarrhea, with very poor prognosis. The authors report the case of a female infant with Down syndrome, aganglionic megacolon, severe diarrhea, and jejunal biopsy with ultrastructural changes consistent with microvillous atrophy. The patient condition improved after a colostomy performed in the setting of the treatment of Hirschprung disease.     

Two novel insulin receptor gene mutations in a patient with Rabson-Mendenhall syndrome: the first Korean case confirmed by biochemical, and molecular evidence

Rabson-Mendenhall syndrome (RMS) is a rare syndrome manifested by extreme insulin resistance with hyperinsulinemia, acanthosis nigricans, tooth dysplasia and growth retardation. Our patient was first noted at the age of 8 months due to pigmentations on skin-folded areas. Initial laboratory tests showed normal fasting glucose (69 mg/dL). Fasting insulin level was severely elevated, up to 554.6 μIU/mL, and c-peptide level was increased, up to 13.81 ng/mL. However, hemoglobin A1c was within normal range (4.8%). He is now 11 yr old. His growth development followed the 5-10th percentile and oral hypoglycemic agents are being administered. The last laboratory results showed insulin 364.1 μIU/mL, C-peptide 4.30 ng/mL, and hemoglobin A1c 7.6%. The boy was a compound heterozygote for the c.90C > A and c.712G > A mutations of the insulin receptor gene, INSR, which are nonsense and missense mutations. In summary, we report the first Korean case of RMS, which was confirmed by two novel mutations of the INSR.     

Effect of zoledronic acid on acro-osteolysis and osteoporosis in a patient with Hajdu-Cheney syndrome

Hajdu-Cheney syndrome is a rare, autosomal dominant skeletal dysplasia marked by acro-osteolysis of the distal phalanges and severe osteoporosis. Although there are more than 60 reports published to date, proper treatment and subsequent outcome have been scarce. Herein, we report a progress of anti-resorptive therapy with zoledronic acid, in a woman with Hajdu-Cheney syndrome. Results suggest that anti-resorptive therapy may be important in delaying the progress of osteoporosis and preventing fractures, but not necessarily acro-osteolysis itself.     

Increased red cell distribution width in patients with slow coronary flow syndrome

OBJECTIVE:

An elevated red cell distribution width has been recognized as a predictor of various cardiovascular diseases. Slow coronary flow syndrome is an important angiographic clinical entity with an unknown etiology. This study aimed to examine the relationship between red cell distribution width and the presence of slow coronary flow syndrome.

METHODS:

In total, 185 patients with slow coronary flow syndrome and 183 age- and gender-matched subjects with normal coronary flow (controls) were prospectively enrolled in this study. Red cell distribution width and C-reactive protein were measured upon admission, and the results were compared between the patients with slow coronary flow syndrome and normal controls.

RESULTS:

Red cell distribution width levels were significantly higher in the patients with slow coronary flow syndrome than the normal controls. Moreover, the data showed that the plasma C-reactive protein levels were also higher in the patients with slow coronary flow syndrome than in the normal controls. In addition, a multivariate analysis indicated that C-reactive protein and red cell distribution width were the independent variables most strongly associated with slow coronary flow syndrome. Finally, the red cell distribution width was positively correlated with C-reactive protein and mean thrombosis in the myocardial infarction frame counts of the patients with slow coronary flow syndrome.

CONCLUSION:

The data demonstrated that red cell distribution width levels are significantly higher and strongly positively correlated with both C-reactive protein and thrombosis in the myocardial infarction frame counts of patients with slow coronary flow syndrome. These findings suggest that red cell distribution width may be a useful marker for patients with slow coronary flow syndrome.     

T-gamma-lymphoproliferative disorder arising in a background of autoimmune disease and terminating in plasma cell dyscrasia with primary amyloidosis

T-gamma-lymphoproliferative disorder, a syndrome of T-cell lymphocytosis with neutropenia has been described in patients with various autoimmune disorders, especially rheumatoid arthritis. We report a case of T-gamma-lymphoproliferative disorder occurring in a 42-year-old white woman with a long history of dermatitis herpetiformis and subsequent development of Coomb's positive autoimmune hemolytic anemia and polymyositis. The peripheral blood lymphocytes showed the T-suppressor cell phenotype (CD2-, CD3-, CD8-, and CD4-). DNA analysis of the peripheral blood lymphocytes revealed a T-cell receptor beta-chain gene rearrangement and an immunoglobulin heavy-chain gene rearrangement. The patient's course was marked by numerous bouts of infection. The unique factor in this patient was the development of a plasma cell dyscrasia and amyloidosis prior to death.     

Variant alveolar lipoproteinosis: a syndrome with distinct clinical and pathological features

Pulmonary alveolar proteinosis (PAP) is a rare condition in which pulmonary macrophages fail to clear surfactant, resulting in the alveolar accumulation of lipoproteinaceous debris. The histopathology of PAP is typified by diffuse filling of terminal airways with eosinophilic, PAS/diastase (PAS/D)-positive acellular material. We present five patients who showed histopathological changes in the lungs consistent with mild PAP. However, these cases were notable for the abundance of degenerating alveolar macrophages, weak PAS staining of lipoproteinaceous material and paucity of lamellated bodies on ultrastructural examination. Only one patient showed the CT finding of mosaiform 'crazy-paving' and the opalescent bronchoalveolar lavage fluid characteristic of PAP. In one case, therapeutic lung lavage based on a presumptive diagnosis of PAP exacerbated respiratory distress. Three patients showed partial or near-complete resolution of disease in response to high-dose corticosteroid therapy, a treatment approach that is generally ineffective in PAP. We conclude that distinguishing 'variant alveolar lipoproteinosis' from classical PAP is clinically important. Despite the otherwise typical appearance of lipoproteinaceous alveolar material in lung biopsies, the presence of degenerating foamy macrophages and atypical histochemical, ultrastructural and radiographic features suggest a steroid-responsive form of proteinosis that is likely pathogenetically distinct and may not be amenable to whole-lung lavage.     

Red blood cell distribution width is associated with myocardial injury in non-ST-elevation acute coronary syndrome

OBJECTIVES:

The red blood cell distribution width has been associated with an increased risk of cardiovascular events. In the present study, we assessed the relationship between red cell distribution width values and cardiac troponin I levels in patients admitted with non-ST-elevation acute coronary syndrome.

METHODS:

We analyzed blood parameters in 251 adult patients who were consecutively admitted to the intensive coronary care unit with non-ST-elevation acute coronary syndrome over a 1-year period. For all patients, a baseline blood sample was collected for routine hematological testing. Cardiac troponin I was measured at baseline and after 6 h. The patients were diagnosed with non-ST-elevation myocardial infarction or unstable angina based on the elevation of cardiac troponin I levels.

RESULTS:

The red cell distribution width was higher in the group with non-ST-elevation myocardial infarction compared with the patient group with unstable angina (14.6±1.0 vs 13.06±1.7, respectively; p = 0.006). Coronary thrombus was detected more frequently in the group of patients with non-ST-elevation myocardial infarction than in the patients with unstable angina (72% vs 51%, respectively; p = 0.007). Using receiver operating characteristic curve analysis for the prediction of non-ST-elevation myocardial infarction based on the red cell distribution width, the area under the curve was 0.649 (95% confidence interval: 0.546-0.753; p = 0.006), suggesting a modest model for the prediction of non-ST-elevation myocardial infarction using the red cell distribution width. At a cut-off value of 14%, the sensitivity and specificity of the red cell distribution width were 73% and 59%, respectively. Additionally, the red cell distribution width was positively correlated with cardiac troponin I (r = 0.19; p = 0.006).

CONCLUSION:

A greater baseline red cell distribution width value was associated with myocardial injury and elevated cardiac troponin I levels in non-ST-elevation acute coronary syndrome. Therefore, the red cell distribution width could be considered for risk stratification of acute coronary syndrome patients admitted to emergency departments.     

Clinical, morphological and biochemical features in the familial articular hypermobility syndrome (FAHS): a family study

A female with clinical features of familial articular hypermobility syndrome (FAHS) and her family were studied. The subject showed generalized hypermobility, except for a painful shoulder which presented functional limitation with a diagnosis of painful shoulder syndrome. Biochemical studies demonstrated that collagen and glycosaminoglycans (GAGs) contents from skin biopsies of the subject and her family were almost normal. Nevertheless, the densitometric analysis of electrophoretic patterns showed differences in the relative proportions of their collagenous components. They were characterized by changes in type I and III collagens and the presence of type V collagen, in the subject, her father and brother. Also, they presented changes in the types of GAGs, when compared with those of normal skin. Morphological studies revealed a general disorganization of dermal components, a loose collagen network characterized by thick bundles. Also, besides cellular elements, the presence of an abundant darkly staining material was observed.
Biochemical and morphological findings permit us to suggest a connective tissue defect, initially described in the FAHS, otherwise known as Ehlers-Danlos syndrome (EDS) type XI.     

Establishment of a monoclonal antibody to plasma cells: a comparison with CD38 and PCA-1

A new monoclonal antibody which recognizes plasma cells was developed by utilizing two myeloma cell lines, KMS12PE (12PE) and KMS12BM (12BM). established from the pleural of fusion and bone marrow, respectively, of the same patient. Since I2BM expresses CD20, CD38, and PCA-I antigens, while 12PE has lost CD20. 12PE is considered to be phenotypically more mature than 12BM. The 12PE cells were used to immunize a BALB/c mouse and a MoAb was produced which was more reactive to 12PE than to 12BM. Thus, a clone, D2, was obtained. On Western blotting, D2 detected a single band of 54 kD under both reduced and non-reduced conditions. This antigen was not detected by Western blotting in peripheral blood lymphocytes that had been stimulated with pokeweed mitogen (PWM) for 7 days or in those not so stimulated. On flow cytometry, D2 detected a myeloma cell line, RPMI 8226. Another myeloma cell line, U266, was negative for D2 antigen. Staining various cell lines by D2 and other antiplasma cell antibodies, PCA-1 and CD38, showed that D2 is distinct from PCA-1 and CD38. The fresh myeloma cells of 14 myeloma patients were stained by D2 and for other plasma cell antigens. D2 strongly stained three samples obtained from patients with clinically aggressive myeloma, while CD38 stained all cases except one. PCA-1 was positive in nine samples and negative in five. PCA-1 expression was observed in plasma cells obtained from pleural effusion and peripheral blood, while PCA-1-negative cases were not found in such samples, suggesting that PCA-I expression was related to extramedullary invasion. The morphology of the myeloma cells, classified according to Greipp's criteria, showed that there was no correlation between plasma cell antigen expression and plasma cell morphology. Analysis of D2 antigen expression should provide more information about the heterogeneity of myeloma cells.