Clinical impact of selective spasm provocation tests: comparisons between acetylcholine and ergonovine in 1508 examinations

BACKGROUND: There are few reports regarding the concordance of coronary arterial response between acetylcholine (ACh) and ergonovine (ER) spasm provocation tests. OBJECTIVES: We attempted to perform selective spasm provocation tests to examine the incidence of provoked spasm in patients who had undergone first coronary angiography as much as possible and we compared the coronary arterial response and clinical usefulness between selective intracoronary injection of ACh and intracoronary administration of ER. METHODS: We performed 1508 selective spasm provocation tests, consisting of 873 ACh tests and 635 ER tests, from 1991 to 2002. We examined the frequency of provoked spasms of each agent retrospectively. ACh was injected in incremental doses of 20, 50 and 80 microg into the right coronary artery and 20, 50 and 100 microg into the left coronary artery. ER was administered as 10 microg/min over 4 min for a maximal dose of 40 microg in the right coronary artery and as 16 microg/min over 4 min for a total dose of 64 microg in the left coronary artery. Coronary spasm was defined as transient >99% luminal narrowing. RESULTS: Intracoronary ACh provoked spasms in 36.0% of patients and intracoronary ER induced spasms in 29.8% of patients. In patients with ischemic heart disease, the incidence of provoked spasms was not different between ACh tests (50.9%) and ER tests (43.8%). In contrast, the frequency of provoked spasms with ACh tests was significantly higher than that with ER tests (11.0% compared with 6.4%, P<0.05) in patients without ischemic heart disease. Moreover, ACh provoked more spasms in patients without fixed stenosis than ER (36.2% compared with 25.5%, P<0.01) and multiple spasms were frequently observed when performing ACh tests (40.0% compared with 27.0%, P<0.01). Major complications were observed in 1.4% of patients with ACh tests and in 0.2% of patients with ER tests. The need for intracoronary administration of isosorbide dinitrate to relieve coronary spasms during ER testing before performing another coronary artery test was more frequently observed in ACh tests (5.04% compared with 1.49%, P<0.01). However, no serious irreversible complications, such as death or acute myocardial infarction, were observed in this study. There was a significant difference in sex, history of smoking and hyperlipidemia between patients with and without spasms for both tests, whereas no difference in age or hypertension was observed in either test. CONCLUSION: Thus, both selective ACh and ER tests were useful as spasm provocation tests.     

Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice

Aims/hypothesis Brain natriuretic peptide (BNP) is a potent vasorelaxing and natriuretic peptide that is secreted from the heart and has cardioprotective properties. We have previously generated hypotensive transgenic mice (BNP-Tg mice) that overproduce BNP in the liver, which is released into the circulation. Using this animal model, we successfully demonstrated the amelioration of renal injury after renal ablation and in proliferative glomerulonephritis. Glomerular hyperfiltration is an early haemodynamic derangement, representing one of the key mechanisms of the pathogenesis of diabetic nephropathy. Based on the suggested involvement of increased endogenous natriuretic peptides, the aim of this study was to investigate their role in the development and progression of diabetic nephropathy. Materials and methods We evaluated the progression of renal injury and fibrogenesis in BNP-Tg mice with diabetes induced by streptozotocin. We also investigated the effect of BNP on high glucose-induced signalling abnormalities in mesangial cells. Results After induction of diabetes, control mice exhibited progressively increased urinary albumin excretion with impaired renal function, whereas these changes were significantly ameliorated in BNP-Tg mice. Notably, diabetic BNP-Tg mice revealed minimal mesangial fibrogenesis with virtually no glomerular hypertrophy. Glomerular upregulation of extracellular signal-regulated kinase, TGF-β and extracellular matrix proteins was also significantly inhibited in diabetic BNP-Tg mice. In cultured mesangial cells, activation of the above cascade under high glucose was abrogated by the addition of BNP. Conclusions/interpretation Chronic excess of BNP prevents glomerular injury in the setting of diabetes, suggesting that renoprotective effects of natriuretic peptides may be therapeutically applicable in preventing the progression of diabetic nephropathy.     

Treatment of high-risk peripheral T-cell lymphomas other than anaplastic large-cell lymphoma with a dose-intensified CHOP regimen followed by high-dose chemotherapy. A single institution study

We investigated the efficacy of a dose-intensified double-CHOP regimen followed by high-dose chemotherapy with or without peripheral blood stem cell transplantation (PBSCT) in 11 patients with four types of peripheral T-cell lymphoma (PTCL). Three of the 4 patients with unspecified PTCL (PTCLu) achieved complete response (CR); 1 patient relapsed and 1 died of secondary leukemia after consolidation therapy. All angioimmunoblastic T-cell lymphoma (AILT) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients achieved CR; 5 of 6 have remained disease free for more than 3 years. The patient with hepatosplenic lymphoma did not achieve CR even after PBSCT and underwent allogenic bone marrow transplantation (allo-BMT). Thus, our regimen appears to be effective for high-risk AILT and SPTCL. However, allo-BMT should be considered for high-risk of PTCLu and hepatosplenic T-cell lymphoma.     

Dye Spraying and Magnifying Endoscopy for Dysplasia and Cancer Surveillance in Ulcerative Colitis

PURPOSE The aim of this study was to investigate detection of dysplasia or colitic cancer with ulcerative colitis by use of magnifying endoscopic observation.METHODS From 1986 through 2000, ulcerative colitis was diagnosed and treated in 886 patients at Kitasato University East Hospital. Of the total, we studied 25 patients in depth: 14 who had dysplasia alone, 5 in whom cancer was diagnosed during follow-up after the detection of dysplasia, and 6 who had colitic cancer.RESULTS Dysplasia was detected in 11 (3.2 percent) of 345 patients with extensive colitis and in 8 (3.7 percent) of 217 with left-sided colitis. Colorectal cancer was diagnosed in nine patients (2.6 percent) with extensive colitis and in two (0.9 percent) with left-sided colitis. Neither dysplasia nor colitic cancer was found in patients with proctitis-type colitis. Endoscopically, dysplasia and early cancer were characterized by granular or nodular protruding mucosa or by lowly protruding or flat mucosa, often associated with redness. Dye-spraying endoscopy was useful for detection. Magnifying endoscopy of ten regions of dysplasia (7 patients) and five early cancers (4 patients) showed IIIS to IIIL type pits or IV type pits. Biopsy of sites showing tumorous pits on magnifying endoscopy revealed dysplasia and early cancer. Observation of the pit pattern was found to be diagnostically useful.CONCLUSIONS Dye spraying and magnifying endoscopy are useful for the detection, targeted biopsy, and diagnosis of dysplasia and colitic cancer in patients with ulcerative colitis.     

Monocyte/Macrophage-Specific Marker CD163+ Histiocytic Sarcoma: Case Report with Clinical, Morphologic, Immunohistochemical, and Molecular Genetic Studies

We report a case of a very rare disorder, histiocytic sarcoma, from a review of our autopsy cases. The neoplastic cells that proliferated in organs throughout the body were large cells containing eosinophilic cytoplasm and pleomorphic nuclei with prominent nucleoli. In the bone marrow, erythrophagocytosis by neoplastic cells was observed. The neoplastic cells were positive not only for lysozymes and CD68 (KP-1, PG-M1, and Ki-M1P) but also for a monocyte/macrophage-specific marker, CD163. In contrast, the results of tests for markers of myeloid cells, lymphoid cells, and epithelial cells were all negative. In a polymerase chain reaction study of paraffin-embedded tissues, analyses for the rearrangement of immunoglobulin heavy chain and T-cell receptor-γ genes were negative. The current World Health Organization diagnostic criteria for histiocytic sarcoma regard immunohistochemical investigation as crucial. In this regard, the highly specific positivity for CD163 in this patient indicates that immunohistochemical staining of CD163 is very useful for the diagnosis of histiocytic sarcoma.     

Isolated ACTH deficiency with Graves' disease: a case report

A 60-year-old man was hospitalized with complaints of general malaise and weight loss. On admission, ACTH and cortisol levels were low, and thyroid function tests revealed hyperthyroidism. These findings and further examination led to a diagnosis of isolated ACTH deficiency (IAD) with Graves' disease. It is known that IAD is frequently associated with thyroid disease, but its association with Graves' disease is rare. The present case is worth noting, because some reports indicate that aggravation of associated Graves' disease may concomitantly aggravate adrenal insufficiency in patients with IAD.     

Immunological detection of severe acute respiratory syndrome coronavirus by monoclonal antibodies

In order to establish immunological detection methods for severe acute respiratory syndrome coronavirus (SARS-CoV), we established monoclonal antibodies directed against structural components of the virus. B cell hybridomas were generated from mice that were hyper-immunized with inactivated SARS-CoV virion. By screening 2,880 generated hybridomas, we established three hybridoma clones that secreted antibodies specific for nucleocapsid protein (N) and 27 clones that secreted antibodies specific for spike protein (S). Among these, four S-protein specific antibodies had in vitro neutralization activity against SARS-CoV infection. These monoclonal antibodies enabled the immunological detection of SARS-CoV by immunofluorescence staining, Western blot or immunohistology. Furthermore, a combination of monoclonal antibodies with different specificities allowed the establishment of a highly sensitive antigen-capture sandwich ELISA system. These monoclonal antibodies would be a useful tool for rapid and specific diagnosis of SARS and also for possible antibody-based treatment of the disease.     

Disease-specific screening for deep venous thrombosis and pulmonary thromboembolism using plasma <Emphasis Type="SmallCaps">d</Emphasis>-dimer values after total knee arthroplasty

We prospectively evaluated the disease-specific features of the early postoperative plasma D: -dimer value and the relationship with deep venous thrombosis and/or pulmonary thromboembolism (DVT/PE) in 95 patients following total knee arthroplasty. Patients in whom DVT/PE was highly suspected were diagnosed by high-resolution multi-detector row computed tomography scanning (MDCT). Forty-nine knees in 46 patients with rheumatoid arthritis (RA, 24 knees) or osteoarthritis (OA, 25 knees) were finally recruited. DVT/PE was detected in 28 (57.1%) of the 49 cases examined by diagnostic MDCT: 12 (50.0%) of the 24 cases of RA, and 16 (64.0%) of the 25 cases of OA. Of these, PE was found in 11 cases (39.2%), but none of them showed clinical symptomatic signs of dyspnea or chest pain. In both RA and OA cases, there were statistically significant differences in the D: -dimer value on postoperative day 3 (P = 0.027) and after day 28 (P = 0.037) between the groups with and without DVT/PE. In OA cases, there were significant differences between the two groups on postoperative days 1 (P = 0.034), 3 (P = 0.020), 5 (P = 0.005), and 7 (P = 0.045), respectively. At the baseline, perioperative D: -dimer levels in the RA group without DVT/PE were higher than in the OA group. However, multivariate logistic regression analysis showed that RA was not a significant risk factor of DVT/PE in comparison with OA. In conclusion, individual evaluation of the D: -dimer level between RA and OA should provide a more precise predictive indicator of early postoperative DVT/PE.     

Usefulness of accelerated exercise following mild hyperventilation for the induction of coronary artery spasm : comparison with an acetylcholine Test

STUDY OBJECTIVES: This study was performed to compare the results of accelerated exercise following mild hyperventilation and a standard acetylcholine (ACh) test for the induction of coronary artery spasm in patients with drug-induced coronary artery spasm. METHODS AND RESULTS: The subjects were 74 patients with angiographically confirmed coronary artery spasm who were examined using accelerated exercise (ie, exercise that was accelerated every minute according to the protocol of Bruce and Horsten) following mild hyperventilation and who were not receiving any medication. ACh was injected in incremental doses of 20 microg and 50 microg into the right coronary artery and incremental doses of 20 microg, 50 microg, and 100 microg into the left coronary artery. Positive coronary spasm was defined as > or =99% luminal narrowing. Accelerated exercise following a mild hyperventilation test was as useful for detecting evidence of ischemia as was an ACh test (48 patients [64.9%] vs 49 patients [66.2%], respectively; not significant). No difference was observed between ischemic changes on ECG as a result of the newly combined method and the occurrence of ACh-induced spasm. ACh-induced coronary vasospasm occurred in 61 patients (82.4%). In the remaining 13 patients, intracoronary administration of ergonovine provoked coronary spasms. No serious irreversible complications were detected as a result of this newly combined method. CONCLUSIONS: The effectiveness of our newly combined procedure is equivalent to that of an ACh test to diagnose patients with coronary artery spasm.     

A significant reduction in serum alanine aminotransferase levels after 3-month iron reduction therapy for chronic hepatitis C: a multicenter, prospective, randomized, controlled trial in Japan

Background Increasing evidence indicates that iron cytotoxicity plays an important role in the pathogenesis of chronic hepatitis C (CHC). However, the biochemical effects of iron reduction therapy on CHC remain to be confirmed in a controlled study. This study aimed to test whether iron removal by repeated phlebotomy improves serum alanine aminotransferase (ALT) levels in patients with CHC.Methods Patients were randomly assigned to an iron reduction therapy or control group. The patients in the treatment group received 3-month iron reduction therapy by biweekly phlebotomy, while the patients in the control group were followed up for 3 months with regular blood tests alone.Results Thirty-three patients completed the 3-month treatment, while 29 patients received the complete follow-up. The serum ALT levels were reduced from 118 ± 79 to 73 ± 39IU/L in the treatment group, but did not change in the control group (106 ± 45 versus 107 ± 48IU/L). Posttreatment enzyme activity was decreased significantly from the baseline. Furthermore, it was significantly lower than the 3-month control level. Although 5 patients withdrew from the study, none was affected by any side effects of repeated phlebotomy that required them to discontinue the treatment.Conclusions This short-term controlled trial demonstrated the biochemical efficacy and safety of iron reduction therapy for patients with CHC.