Cardiac amyloidosis is a fatal disorder which develops on the basis of the different pathologic conditions in systemic amyloidosis: the most common underlying disease is immunoglobulin light chain-derived primary amyloidosis and the next is transthyretin-related hereditary amyloidosis; the latter disorder, typically represented by familial amyloid polyneuropathy, was long regarded as an endemic disease. However, this disorder has now been shown to involve a highly variable clinical picture due to a large number of transthyretin gene mutations, and many patients with diverse ancestors suffer from severe cardiac amyloidosis. Additionally, senile systemic amyloidosis is now noted as a cause of cardiac dysfunction in elderly individuals. Echocardiogram and myocardial technetium-99m-pyrophosphate scintigraphy can provide characteristic findings. Immunohistochemistry on tissue amyloid, biochemical analysis of serum and urine proteins, and DNA sequencing are usually employed to determine the disease-related amyloid fibril protein. Although systemic amyloidosis has become treatable, the prognosis of each patient who received up-to-date and effective, but nevertheless stressful, therapy depends on the severity of cardiac involvement by amyloid deposition.
Recently there has been considerable interest in a novel surrogate marker of endothelial injury, endothelial microparticles (EMP), in a number of diseases characterised by endothelial injury. This review examines the data relating to EMP in human disease states, and examines the potential for EMP to provide a window onto the activated endothelium in primary systemic vasculitides. The utility of EMP for the diagnosis and monitoring of active vasculitis is discussed.
Objective, /b> Recently, the cases of early gastric carcinomas which can be treated by endoscopic submucosal dissection (ESD) method have been increasing in our institute. Simple and precise guidelines for treating mucosal gastric carcinoma are necessary for improving the treatment outcome of this disease. In our institute, ESD using an insulated-tip diathermic knife (IT-ESD) was introduced for the treatment of mucosal gastric carcinoma in 1996. The purpose of this study was to evaluate the impact of a clinical pathway and standardize the treatment for mucosal gastric carcinoma treated with IT-ESD. Materials and Methods The Clinical Pathway and standardized of treatment for mucosal gastric carcinoma treated with IT-ESD were introduced at our institute in January 2002. We compared the length of hospitalization, total costs, hospital costs, operation time and bleeding rate during the 18 months before and after January 2002. Results There was no significant difference in the clinical characteristics of the 20 patients in the control group and the 23 patients in the pathway group. There were 9 and 13 bleeding cases in the respective groups. The mean length of hospitalization, total costs and hospital costs were significantly less for patients in the pathway group. There was no significant difference in the operation time or bleeding rate among the two groups. Conclusion Our clinical pathway and the standardization of treatment for mucosal gastric carcinoma treated with IT-ESD proved effective for treating patients with mucosal gastric carcinoma and for minimizing the length of hospitalization without compromising patient care.
Objective We analyzed the accumulation of a mitochondrial A-to-G mutation at nucleotide position 3243 (A3243G) in the stomach and gastric motility in patients with gastric symptoms, post-prandial nausea/vomiting and epigastralgia. Methods Detection and quantification of A3243G mutation in mtDNA in the gastric mucosa, oral mucosa, leukocyte, and skeletal muscle were performed. Gastric motility was evaluated by gastric myoelectrical activity on electrogastrography (EGG), and gastric emptying was evaluated by measurement of plasma paracetamol concentration before and after meals. Patients or Materials Four patients with A3243G mutation in the leukocyte mtDNA and gastric symptoms were examined. Results The A3243G mutation was detected at higher percentages in the gastric body (69-94% for mutation; mean, 83%) than in the angle portion (37-82%; mean, 52%), the antrum (40-84%; mean, 57%) or leukocytes (28-52%; mean, 39%), and at slightly higher percentages than in the skeletal muscles (45-87%; mean, 70%) or oral mucosae (52-86%; mean, 69%) in the four patients examined. Abnormal EGGs were observed in the three patients examined. The pre-prandial myoelectrical activities were low in these patients (49% in patient 1, 54% in patient 2, 63% in patient 3; normal >70%). The plasma concentrations of paracetamol were low (3.6 μg/ml in patient 1, 2.4 μg/ml in patient 2, <2.0 μg/ml in patient 3; normal, 7-12 μg/ml). Conclusion Accumulation of mitochondrial A3243G mutation in the stomach is a contributory factor in gastric dysmotility and gastric symptoms in patients with the mutation in their leukocytes.
Background Heavy drinkers have a high incidence of chronic pancreatitis (CP), but the mechanism of alcohol-related CP is largely unknown. Exocrine pancreatic insufficiency exists in about 90% of the patients with cystic fibrosis (CF), which results from an abnormal cystic fibrosis transmembrane conductance regulator gene (CFTR). Aim To investigate in Japanese alcoholics the association between bicarbonate concentration in pure pancreatic juice and one of the polymorphisms of the CFTR gene, the (TG)m Tn tract length in intron 8. Methods Fifty-six patients under treatment for alcohol dependence were stimulated by intravenous injection of secretin during endoscopic retrograde cholangiopancreatography to provide pancreatic juice specimens. Individual maximum bicarbonate concentrations (MBC) were compared with (TG)m Tn tract polymorphisms identified by directly sequencing lymphocyte DNA. Results Among the 41 patients able to provide adequate pancreatic juice specimens, 15 had low MBC and 26 had normal MBC. The frequencies of the six haplotypes identified in these patients were 17.1% (TG)11T7/(TG)11T7, 46.3% (TG)11T7/(TG)12T7, 29.3% (TG)12T7/(TG)12T7, 2.4% (TG)10T9/(TG)11T7, 2.4% (TG)12T5/(TG)11T7, and 2.4% (TG)12T6/(TG)12T7. Among the 92.7% of patients who had the common (TG) m1T7/(TG)m2T7 haplotype, all of the 7 with homozygous (TG)11 alleles had normal MBC (p<0.05). Conclusion Alcoholics with homozygous (TG)11 alleles in intron 8 of the CFTR gene appear to be protected against decreased MBC, compared with those who have the (TG)11/(TG)12 and (TG)12/(TG)12 genotypes, suggesting a role for CFTR gene polymorphism in the progression of alcohol-related pancreatic disease.
Objective To clarify the contributions of visceral fat tissue (VAT) mass deposition to the accumulation of risk factors for atherosclerosis in normal weight subjects. Subjects and Methods We investigated the relationship between VAT accumulation and both risk factors and waist circumference in non-obese subjects. In the 955 normal weight Japanese subjects (782 men and 173 women), visceral fat area (VFA), subcutaneous fat area (SFA) and waist circumference were measured through computed tomography. Total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, uric acid, fasting blood glucose, and 2-hour postprandial glucose in the oral glucose tolerance test (OGTT) were measured to assess the risk factors for atherosclerosis. Results In both men and women with normal body weight, VFA was correlated with total cholesterol (r=0.78 and r=0.71, respectively), HDL cholesterol (r=−0.89 and r=−0.82, respectively), triglyceride (r=0.72 and r=0.91, respectively), uric acid (r=0.71 and r=0.69, respectively), fasting blood glucose (r=0.84 and r=0.82, respectively), OGTT 2-hour postprandial glucose (r=0.75 and r=0.50, respectively), and systolic (r=0.93 and r=0.73, respectively) and diastolic (r=0.91 and r=0.73, respectively) blood pressure. The average number of risk factors was also correlated with VFA both in men (r=0.88, p=0.005) and women (r=0.91, p=0.003) with normal body weight. Based on the results of the multiple regression analyses, among VFA, SFA, body mass index (BMI) and age, VFA was considered to be the most important predictor for explaining the average number of risk factors. We also demonstrated that VFA was correlated with the waist circumference in normal weight men (r=0.74) and women (r=0.59). In normal weight subjects, the waist circumference equivalent to more than 1.0 of the average number of risk factors was 81 cm in men and 89 cm in women. Conclusion VAT accumulation itself plays a role as a risk factor for atherosclerosis irrespective of BMI, and measurement of VFA may be more important than that of BMI for predicting the presence of risk factors in normal weight subjects. Measurement of waist circumference also might be important for assessing the possibility of VAT accumulation leading to atherosclerosis.
We report a case of barium intravasation in a 66-year-old patient. Unenhanced computed tomography (CT) scan revealed barium and air emboli in portal veins and liver. We believe he survived because his liver prevented inflow of barium into the systemic circulation. To the best of our knowledge, this is the 23rd reported case of venous barium intravasation in the last 50 years. Because all 23 patients had bowel disease or diverticulitis, we conclude barium enema should be used cautiously in such patients.
A 64-year-old man with a chief complaint of melena visited our emergency outpatient clinic. After several examinations, he was diagnosed as a gastrointestinal stromal tumor (GIST) with liver metastasis. Surgical resection of the jejunal lesion and postoperative adjuvant therapy with STI571 for one year was performed. Due to recent immunohistological studies and introduction of STI571, the diagnosis, treatment, and prognosis of GIST are about to change profoundly. Further accumulation of cases is necessary to investigate the diagnosis, treatment, and prognosis of GIST.
A 28-year-old man was admitted because of chest pain. Emergency coronary angiography showed a massive thrombus in the proximal segment and another occlusive thrombus in the distal segment of the left anterior descending artery. He was treated with thrombolytic therapy. Repeat coronary angiography showed disappearance of the thrombi in the proximal and distal segments and obvious myocardial bridging in the mid segment. Intravascular ultrasound revealed an atherosclerotic plaque in the segment immediately proximal to the myocardial bridging, but did not reveal any plaque within or distal to the site. He was discharged 12 days later.
Autonomic disturbance develops commonly in neuroleptic malignant syndrome (NMS). However, the association of cardiomyopathy is rare. Takotsubo-shaped cardiomyopathy is a unique reversible heart syndrome involving autonomic disturbance and mimicking myocardial infarction. We report a 63-year-old woman who developed Takotsubo-shaped cardiomyopathy during the course of NMS. Our case suggests the occurrence of reversible cardiomyopathy as the autonomic involvement of NMS.
A 49-year-old man was admitted to our hospital due to chest oppressive sensation. Coronary angiography showed total occlusion in the proximal right coronary artery even after intracoronary nitroglycerin, but no stenosis in the left coronary artery. He was treated with aspiration thrombectomy and stent deployment. After 23 hours, he suddenly had severe chest pain, and ECG showed marked ST elevation in leads I, aVL and V2-6. Surprisingly, coronary angiography showed total occlusion in the proximal left anterior descending artery even after intracoronary nitroglycerin where there had been no stenosis on first angiogram just 23 hours earlier. He was treated with aspiration thrombectomy.
Pseudoxanthoma elasticum (PXE) is a rare, inherited, systemic disease of elastic tissue that in particular affects the skin, eyes, and cardiovascular system. Recently, the ABCC6 (MRP6) gene was found to cause PXE. A defective type of ABCC6 gene (16p13.1) was determined in two Japanese patients with PXE. In order to determine whether these patients have a defect in ABCC6 gene, we examined each of 31 exons and flanking intron sequences by PCR methods (SSCP screening and direct sequencing). We found two novel missense variants in exon 26 and 29 in a compound heterozygous state in the first patient. One is a missense mutation (c.3661C>T; p.R1221C) in exon 26 and the other is a missense mutation (c.4069C>T; p.R1357W) in exon 29. These mutations have not been detected in our control panel of 200 alleles. To our knowledge, this is the first report of mutation identification in the ABCC6 gene in Japanese PXE patients. The second patient was homozygous for 2542_2543delG in ABCC6 gene and heterozygous for 6 kb deletion of LDL-R gene. This case is the first report of a genetically confirmed case of double mutations both in PXE and FH loci.
We report the first case of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with cytomegalovirus (CMV) infection. A 32-year-old woman was admitted to our hospital because of pandysautonomic signs and symptoms. Thrombocytopenia and hyponatremia were present. Serum anti-CMV IgM and IgG antibodies were positive. Despite hyponatremia, urinary osmolality exceeded plasma osmolality and plasma vasopressin levels related to plasma osmolality were high. Restriction of water intake and administration of dimethylchlorotetracycline improved hyponatremia, suggesting this patient had SIADH. In this patient, SIADH may have been caused by acute pandysautonomia that developed following CMV infection.
A 81-year-old woman was diagnosed as having diabetes mellitus (DM) at 58 years of age. She started insulin therapy the following year, but her blood sugar levels were poorly controlled. At the age of 75, she tested positive for the anti-GAD antibody (7.8 U/ml) and was diagnosed as having slowly progressive type 1 DM (SPIDDM), as well as vitiligo vulgaris. At 78 years of age, chronic thyroiditis was diagnosed after positive tests for anti-thyroid peroxidase antibody and anti-thyroglobulin antibody. At the age of 81, general fatigue and jaundice appeared concomitantly with severe anemia, with Hb levels at 5.2 g/dl. Low serum vitamin B12 levels and the finding of erythroblastic hyperplasia with megaloblasts in bone marrow led to the diagnosis of pernicious anemia. Anemia was alleviated by intramuscular injections of vitamin B12. The patient developed chronic thyroiditis, vitiligo vulgaris, and pernicious anemia concomitantly with SPIDDM, and was diagnosed as having polyglandular autoimmune syndrome type III. Attention should be paid to these potentially associated autoimmune diseases in daily practice during the follow-up of SPIDDM patients.
A 28-year-old man presented with mental retardation, peculiar facial features, radioulnar synostosis, hypogonadism, aplasia of the right kidney, a moderate degree of proteinuria, and peripheral cyanosis. The activated partial thromboplastin time was shortened, and the level of plasma factor VIII was high. A chromosomal analysis revealed a 49, XXXXY karyotype. From the 10th hospital day, he suffered from sudden dyspnea following swelling of the left leg. He was diagnosed as having deep vein thrombosis and pulmonary embolism, and was successfully treated with anticoagulant therapy. This is the first case of the 49, XXXXY syndrome complicated with unilateral renal aplasia, proteinuria, and venous thromboembolism.
Primary mediastinal seminoma is a relatively rare tumor usually located in the anterior mediastinum. We report here an extremely rare case of a 66-year-old man with primary seminoma in the middle mediastinum. A physical examination showed lymphadenopathy in the right supraclavicular area. A chest CT confirmed the presence of a tumor occupying the retrotracheal space. A histological examination demonstrated metastatic seminoma from the open biopsy of the lymph node. Abdominal, pelvis, and cerebral CT scan and testicular ultrasound were negative. Thus, primary mediastinal seminoma in the middle mediastinum with supraclavicular lymph node metastasis was diagnosed.
Pulmonary edema, both cardiogenic and noncardiogenic, has been reported as a manifestation of pheochromocytoma. We report a patient with pheochromocytoma complicated by acute pulmonary edema that appeared clinically noncardiogenic. The patient had an uncomplicated course and rapid resolution of pulmonary edema. Bronchoalveolar lavage fluids (BALF) showed a marked accumulation of neutrophils, suggesting involvement of neutrophil-mediated lung injury in noncardiogenic pulmonary edema associated with a pheochromocytoma.
Diffuse pulmonary small nodules and pyrexia suddenly developed in a 27-year-old woman during immunosuppressive treatment for viral-associated hemophagocytic syndrome. Miliary tuberculosis was suspected, however, bone marrow biopsy did not support the diagnosis. Lung biopsy revealed interstitial pneumonitis admixed with characteristic inclusion-bearing cells, and cytomegalovirus (CMV) DNA was demonstrated in polymerase chain reaction using bronchoalveolar lavage cells, establishing the diagnosis of CMV pneumonitis. No other opportunistic pathogens were identified, and the pneumonitis was subsided due to administration of gancyclovir. The present case illustrates CMV pneumonitis as a differential diagnosis for small nodular opacities which develop in immunocompromised patients.
A 49-year-old Japanese man with rheumatoid arthritis acutely developed a skin eruption and severe non-productive cough seventeen days after the administration of leflunomide. Because all bacteriology findings were negative, steroid pulse-therapy was initiated promptly due to the rapidity of chest X-ray progression and the deterioration of arterial blood oxygen pressure. Although cough was induced by methotrexate, interstitial pneumonia was not detected clinically before leflunomide administration. He finally died of respiratory failure 128 days after the onset of acute interstitial pneumonia. According to the post-market surveillance, as high as ∼1.1 % of the patients on leflunomide have developed interstitial pneumonia in Japan. It is important to emphasize that acute interstitial pneumonia due to leflunomide is a very severe and potentially fatal side effect.
Primary varicella infection in immunocompetent adults is very rare, but it has a high mortality rate because of serious complications. We describe a case of varicella infection in a previously healthy young adult complicated with acute respiratory distress syndrome (ARDS), rhabdomyolysis, acute hepatitis and disseminated intravascular coagulation (DIC). Acyclovir was administered for varicella infection and the ARDS was successfully treated with steroidpulse therapy, hemofiltration and a mechanical respiratory support with a positive end-expiratory pressure. Early administration of antiviral agents and extensive management were thought to be necessary for such patients with severe complications.