Confirmation of Age-dependence in the Leakage of Contrast Medium around the Cortical Veins into Cerebrospinal Fluid after Intravenous Administration of Gadolinium-based Contrast Agent

Purpose:It has been reported previously that intravenously administered gadolinium-based contrast agent (GBCA) leaks into the subarachnoid space around the cortical veins at 4 h after injection in all old people over 37 years, but not in younger people up to 37 years of age in 3D-real IR images. The purpose of this study was to investigate whether there was a strict threshold of 37 years of age for the leakage of the GBCA into the subarachnoid space.Methods:The subjects included 190 patients, that were scanned for 3D-real IR images at 4 hours after intravenous injection of GBCA as a diagnostic test for endolymphatic hydrops. The patient’s age ranged from 14 to 81 years. Two experienced neuroradiologists evaluated the images to determine whether the GBCA leakage around the cortical veins was positive or negative. Any discrepancies between the two observers were discussed and a consensus was obtained.A Mann–Whitney U test and receiver operating characteristic (ROC) curve analysis were used to compare the positive and the negative group and to set the age cut-off value for the prediction of GBCA leakage.Results:The GBCA leakage around the cortical veins was negative in 35 patients and positive in 155 patients. The average age was 33 ± 11 years in the negative group, and 55 ± 12 years in the positive group (P < 0.01). In the ROC analysis for the age and leakage of the GBCA, an area under the curve was 0.905 and the cut-off age was 37.317 years (sensitivity of 0.942 and specificity of 0.771).Conclusion:Intravenously administered GBCA leaks into the subarachnoid space around the cortical veins in most patients over 37 years of age. However, it should be noted that it can be found occasionally in patients under 37 years of age.     

Treatment of HTLV-I-associated myelopathy with high-dose intravenous gammaglobulin

Summary Fourteen patients with HTLV-1-associated myelopathy were treated with high-dose intravenous gammaglobulin (IVGG). Ten received 10 g/day of IVGG and 4 received 400 mg/kg of body-weight/day of IVGG for 5 consecutive days. Improvement of spastic paraparesis was observed in 10 within 7 days of the commencement of IVGG. The therapeutic effects were sustained for more than 3 weeks in some patients. There were no side effects. Analysis of factors of relevance to the clinical improvement with IVGG showed that the beneficial response was preferentially found in patients having a high CSF titre of anti-HTLV-I antibodies, a high CSF IgG level and a marked brain MRI abnormality.     

Immunochemical studies of human prolidase with monoclonal and polyclonal antibodies: absence of the subunit of prolidase in erythrocytes from a patient with prolidase deficiency

Prolidase was highly purified from human liver and erythrocytes. NaDodSO4/acrylamide gel electrophoresis revealed that these preparations contained a major protein with MW = 56,000. The mass of prolidase was estimated on gel filtration to be MW = 97,000, for both enzyme preparations. A monoclonal antibody was raised against the liver enzyme and a specific antiserum against the erythrocyte enzyme. The monoclonal antibody (EP-2) recognized prolidase from erythrocytes and liver, in equal proportions. The antiserum also recognized the enzyme from erythrocytes and liver. Immunoprecipitation studies with these antibodies suggested only a single species of prolidase in erythrocytes and liver. Using an immobilized monoclonal antibody (EP-2) as an immunoadsorbent, prolidase was partially purified from crude extracts, and the protein of the partially purified enzyme was identified by immunoblotting using antiserum. A protein band with a MW = 56,000 was demonstrated specifically when crude extracts from the liver and erythrocytes were examined using NaDodSO4/acrylamide gel electrophoresis. The subunit protein was absent in erythrocytes from a patient with prolidase deficiency. We propose that the absence of the subunit is one cause of the prolidase deficiency.     

The correlation of the treadmill exercise test with cardiac hemodynamics in patients with previous myocardial infarction

The correlation between the treadmill exercise test results and the hemodynamic data of 152 patients with previous myocardial infarction were investigated. The patients were classified into 4 groups as follows: H1 left ventricular end-diastolic pressure (LVEDP) less than or equal to 12 mmHg and cardiac index (CI) greater than or equal to 3.0 L/min/m2; H2 LVEDP greater than 12 mmHg and CI greater than or equal to 3.0 L/min/m2; H3 LVEDP less than or equal to 12 mmHg and CI less than 3.0 L/min/m2; and H4 LVEDP greater than 12 mmHg and CI less than 3.0 L/min/m2. The duration of the exercise was significantly shortened for group H4 than group H1 (p less than 0.01). The maximal ST segment elevation (mSTe) was significantly increased for group H3 and group H4, versus group H1 (p less than 0.05). The number of ST segment elevations and mSTe/maximal heart rate were significantly increased for group H3 (p less than 0.05) and group H4 (p less than 0.01) versus group H1. The incidence of exercise-induced premature ventricular contractions (PVCs) was significantly increased in group H3 and group H4, versus group H1 (p less than 0.05). There were no significant differences in the maximal heart rate, double product, and ST segment depression among the 4 groups. Our data indicate that the groups with impaired left ventricular functions tend to decrease the duration of the exercise and to increase ST segment elevation and PVC frequencies during exercise.     

St. Jude Medical valve replacement: clinical experience with 1,039 patients

St. Jude Medical valve replacement was performed in 1,039 patients; 320 had aortic (AVR), 543 mitral (MVR), and 176 had double valve replacement (DVR). There were 44(4.2%) early deaths. Follow-up extended in 995 patients from 10 to 130 months, with a cumulative period of 2,730 patients-years. The overall survival rates of AVR, MVR, and DVR patients at 10 years were 60.5%, 89.6%, 90.3% respectively. The linearized incidences of valve thrombosis, thromboembolism, anticoagulation-related hemorrhage, prosthetic valve endocarditis, and significant hemolysis were as follows: 0.11%/pt-yr, 1.33%/pt-yr, 0.04%/pt-yr, 0.18%/pt-yr, and 0.11%/pt-yr, respectively. There were no structural failure after 10 years follow-up. Reoperation (explant and re-replacement or suture repair) was required in 10 patients. Seven of them had periprosthetic leakage, 2 had valve thrombosis, and one underwent reoperation because of a technical error. Actuarially over 98% of patients were free of valve-related mortality at 10 years. St. Jude Medical valve is an excellent alternative for use in the surgical treatment of valvular heart disease.     

A case of parathyroid hormone-related peptide producing gallbladder carcinoma presenting humoral hypercalcemia of malignancy]

Humoral hypercalcemia of malignancy (HHM) in neoplastic syndrome has been most commonly reported in squamous cell carcinoma. Gallbladder carcinoma with HHM is uncommon. In this report, we describe a male case of gallbladder carcinoma with marked hypercalcemia and a high level of serum parathyroid hormone-related peptide (PTHrP). An immunohistochemical examination using PTHrP was also positive.     

Big mitogen-activated protein kinase 1 (BMK1)/extracellular signal regulated kinase 5 (ERK5) is involved in platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell migration

Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling.