Nicorandil suppresses the increases in plasma level of matrix metalloproteinase activity and attenuates left ventricular remodeling in patients with acute myocardial infarction

Nicorandil, a hybrid K_ATP channel opener and nicotinamide nitrate, reduces no-reflow phenomenon and improves cardiac function in patients with acute myocardial infarction (AMI). We repoted that nicorandil suppresses radical formation in patients with AMI undergoing primary percutaneous coronary intervention (PCI). In the present study, we tested the hypothesis that nicorandil treatment suppresses MMP activities and predicts ventricular remodeling in AMI. Sixty-two patients with AMI were randomized into nicorandil pretreatment (n = 31) and control (n = 31) groups after admission and underwent primary PCI. Nicorandil was administered as a bolus injection (4 mg) followed by constant infusion (8 mg/h) for 24 h just after admission. On days 1, 2, and 14 after the onset of AMI, the plasma levels of matrix metalloproteinase (MMP)-2 and MMP-9 were measured by enzyme-linked immunosorbent assay and the activities by gelatin zymography. There were no differences in the baseline clinical characteristics between the two groups. On day 1, there were no differences in both MMP-2 and MMP-9 levels and their activities between the two groups. However, both MMP-2 and MMP-9 levels and their activities were significantly lower in nicorandil than in control group on day 2 (MMP-2 level, 1 014 ± 39 vs 1 174 ± 44 ng/ml; MMP-9 level, 17 ± 1 vs 23 ± 2 ng/ml; both P < 005) and on day l4 (MMP-2 level, 970 ± 38 vs 1 221 ± 44 ng/ml; MMP-9 level, 17 ± 1 vs 23 ± 1 ng/ml; both P < 0.05). Left ventricular end-diastolic volume index (LVEDVI) at acute phase was not different between the two groups. At 6 months after AMI, LVEDVI was significantly smaller in nicorandil than in the control group (83 ± 4 vs 96 ± 4 ml/m², P < 0.05). The change in LVEDVI from acute phase to 6 months was positively correlated with MMP-2 and MMP-9 levels and activities. Nicorandil suppresses the increases in MMP levels and activities and prevents the development of ventricular remodeling in AMI.     

Acute coronary syndrome due to coronary thrombus formed by severe coronary spasm: a case report

A 47-year-old man was admitted to our hospital complaining of chest pain at rest in the early morning. Electrocardiography showed ST segment elevation in leads II, III and aVF. Emergency coronary angiography revealed total occlusion of the right coronary artery at the proximal portion. Intracoronary administration of isosorbide dinitrate successfully recanalized the right coronary artery. However, there was a thrombus image at the culprit lesion. Intracoronary administration of urokinase caused the residual thrombus to disappear completely. Follow-up coronary angiography at 1 week and 3 months revealed no organic stenotic lesion. Intravascular ultrasound showed only a little plaque without signs of ruptured plaque in the right coronary artery. Provocation coronary angiography revealed remarkable spasm causing total occlusion at the proximal portion of the right coronary artery. This case suggests that only severe coronary spasm without plaque rupture could form a thrombus causing acute coronary syndrome.     

An infant case of macroprolactinemia with transient idiopathic central precocious puberty

Macroprolactinemia was recognized more than a decade ago as a cause of hyperprolactinemia and the prevalence of macroprolactinemia is thought to be 10%-26% of patients with hyperprolactinemia. However, there are few published reports about macroprolactinemia in childhood. We report a 7-year-and-1-month-old girl with hyperprolactinemia due to macroprolactinemia with the complication of transient idiopathic central precocious puberty (ICPP). At the age of 6 years and 9 months, she was diagnosed with ICPP at another clinic, on the basis of isolated mammary development and increased height velocity with slightly advanced bone age. At that time, the unexpected finding of high PRL level was also observed. Four months later, she was referred to our clinic for persistently high PRL level. At this time, other endocrinological data showed prepubertal stage and we demonstrated macroprolactinemia and the presence of anti-PRL autoantibody. After other causes of hyperprolactinemia such as prolactinoma and stress were ruled out, we finally diagnosed her with hyperprolactinemia due to macroprolactinemia. Because most patients with macroprolactinemia are symptom-free despite hyperprolactinemia and drug therapy would not be indicated, macroprolactinemia should be suspected even in children to avoid unnecessary examinations and treatments.     

Long-term effect of combination therapy with mitiglinide and once daily insulin glargine in patients who were successfully switched from intensive insulin therapy in short-term study

We have previously reported the therapeutic efficacy of mitiglinide combined with once daily insulin glargine (mitiglinide regimen) after switching from multiple daily insulin regimen of aspart insulin and glargine (intensive insulin regimen) in inpatients with type 2 diabetes mellitus in two consecutive days. In the present study, we followed up 9 of the 15 responsive patients with these novel regimens for 6 months after discharge. The data collected from these patients were compared to those of 15 randomly chosen patients who had well matched background and received intensive insulin regimen during hospitalization which was continued after discharge. The average HbA1c level of these 9 patients with mitiglinide regimen at 6 months was 6.7 +/- 0.8% and was comparable to that of the patients with intensive insulin regimen (HbA1c = 7.0 +/- 1.0%). In conclusion, mitiglinide and insulin glargine combination therapy maintained fair glycemic control for as long as 6 months in subpopulation of Japanese patients with type 2 diabetes.     

Treatment of Mcleod Phenotype Chronic Granulomatous Disease with Reduced-Intensity Conditioning and Unrelated-Donor Umbilical Cord Blood Transplantation

Patients with chronic granulomatous disease (CGD) complicated by antimycotics-refractory invasive aspergillosis have an extremely poor prognosis if they cannot undergo allogeneic hematopoietic stem cell transplantation from a suitable related donor while in good clinical condition. We successfully treated a 20-year-old man with very rare McLeod phenotype CGD with reduced-intensity conditioning and unrelated-donor umbilical cord blood transplantation. We postulate that reduced-intensity conditioning-allogeneic hematopoietic stem cell transplantation is a promising therapeutic strategy for patients with CGD even if only unrelated-donor umbilical cord blood is available.     

Adverse events of MVAC chemotherapy in patients with advanced urothelial cancer of the bladder

There have only been a few reports about adverse events of methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy under supportive care with granulocyte stimulating factor (G-CSF) and 5-hydroxytryptamine 3 receptor (5-HT3R) antagonists. The purpose of this study was to retrospectively review the adverse events of the chemotherapy. We analyzed 59 patients with advanced bladder cancer who received MVAC chemotherapy at Sapporo Medical University hospital from January 1992 to September 2004. The adverse events were evaluated according to the Common Terminology Criteria for Adverse Events version 3.0 (Japanese edition). Thirty-one of the 59 patients (52.6%) received MVAC in the neoadjuvant setting. Two courses of chemotherapy were most frequently used in the neoadjuvant and adjuvant settings, and treatment of metastatic or recurrent lesions. More than 90% of patients experienced hematological adverse events such as some grade of leukocytopenia and neutropenia in each course of the chemotherapy. Grade 3 or 4 neutropenia was seen in 60-75% of patients. Grade 3 or 4 leukopenia and/or neutropenia in the first course of the chemotherapy was associated with patients with impaired renal function (60 mL/min< or = creatinine clearance <80 mL/min). Febrile neutropenia was found in 6 patients (5.0%), including one who died of subsequent septic shock and adult respiratory distress syndrome. Nausea was seen in 70-80% of patients. MVAC chemotherapy for advanced bladder cancer was performed with tolerable adverse events. The current results provide relevant information mainly for those who need 2 courses of chemotherapy in the neoadjuvant or adjuvant setting.     

Priapism complicated by chronic myelogenous leukemia (CML); a case report

A-29-year-old man visited our hospital with the complaint of a continuous rigid and painful erection which began two days before. We diagnosed ischemic type of priapism by aspiration of penile cavernosal blood analysis; an acidotic and hypoxic blood. The leukocyte count was 263,000/p, and chronic myelogenous leukomia (CML) was suspected. After the failure of conservative treatment, glans-cavernosal shunt (Winter procedure) was performed. The postoperative course was uneventful and the intercourse was possible at five months after the operation. CML was treated by administration of imatinib mesylate and no evidence of recurrence was observed.     

Clinical characteristics of urolithiasis with stone analysis conducted over a 26-year period

OBJECTIVE: Stone analysis is an important examination for treatment and prevention of recurrence in urolithiasis. A twenty-six years clinical study of patient with urinary stone formers performed stone analysis was conducted. MATERIALS AND METHODS: 1,108 stone formers (male 726, female 382) who performed stone analysis from 1977 to 2002 was conducted. Location of the stone, sex, age, treatment and stone analysis was examined in this study. Phase 1 is from 1977 to 1983 mainly performed open surgery, phase 2 is from 1984 to 1992 mainly performed endoscopic surgery, and phase 3 is from 1993 to 2002 mainly performed extracorporeal shock wave lithotripsy (SWL). RESULTS: Analytic numbers per year increased, especially phase 3. In the treatment of upper urinary tract (UUT) stone, open surgery, endoscopic surgery and SWL was carried out 78.4%, 72.8% and 71.4% of all cases in each phase. Many transurethral lithotripsy were performed for lower urinary tract (LUT) stone. The numbers of UUT and LUT stone were 1,007 and 101 cases. The frequency of LUT stone was higher than that found in a nationwide urolithiasis survey carried out in Japan in 1995. The male-female ratio of UUT stone was 2.35:1, 1.74:1 in phase 2 and 3. The frequency of female increased in phase 2 more than that in phase 3. The incidence of calcium oxalate stone was increased, calcium phosphate stone and infectious stone was significantly decreased in UUT and calcium containing stone in LUT was decreased. The average age for incidence of UUT stone rose in man step by step. The frequency in male was significantly higher than that in female under 50's, not significantly higher over 50's in calcium oxalate with calcium phosphate stone former (p = 0.009). CONCLUSION: In the present study, the clinical features were as follows : important urinary stone analysis, high frequency of LUT stone, high frequency in females, tendency to aging, high frequency of calcium containing stone in LUT, resolution of the difference in male and female over 50's in calcium oxalate with calcium phosphate stone former.     

Tumor location affects the results of simple excision for multiple osteochondromas in the forearm

BACKGROUND: The effectiveness of excision of osteochondromas in controlling the progression of forearm and wrist deformity remains an issue of controversy. The purpose of this study was to analyze the effectiveness of tumor excision in the correction of forearm and wrist deformity due to multiple osteochondromas in children, with an interpretation of the results based on different patterns of deformity. METHODS: Fourteen forearms in thirteen children with a follow-up of more than twenty-four months (average, fifty-three months) were included in the study. The forearms were divided into two groups on the basis of the location of the tumor and the pattern of deformity. In Group 1 (six forearms), the osteochondroma was only in the distal aspect of the ulna and caused compression of the radius. In Group 2 (eight forearms), tumors were in both the distal aspect of the ulna and the ulnar side of the distal part of the radius and were in contact with each other. Radial length, ulnar shortening, radial bowing, the radial articular angle, and carpal slip were measured as radiographic parameters. Ulnar shortening and radial bowing were expressed as a percentage of the radial length to make it possible to compare data between the individuals. Each parameter was evaluated before surgery and at the time of final follow-up. RESULTS: In Group 1, the percentage of ulnar shortening and the percentage of radial bowing had improved at the time of final follow-up; however, in Group 2, both the radial articular angle and the percentage of radial bowing had deteriorated significantly after the tumor excision (p = 0.049 and p = 0.017, respectively), even though the percentage of ulnar shortening showed no change. CONCLUSIONS: The effectiveness of simple excision of osteochondromas of the distal aspect of the forearm is influenced by the tumor location and is related to the pattern of the deformity. Simple tumor excision can correct the forearm deformity in patients with an isolated tumor of the distal part of the ulna. Conversely, in patients with tumors involving the distal part of the ulna and the ulnar side of the distal end of the radius, tumor excision alone is a less promising procedure for the correction of the deformity. LEVEL OF EVIDENCE: Prognostic Level IV.