Early use of beta-blockers is associated with attenuation of serum C-reactive protein elevation and favorable short-term prognosis after acute myocardial infarction

BACKGROUND: We have reported that a marked elevation in serum C-reactive protein (CRP) level is a predictor for infarct expansion and cardiac rupture after AMI. Although beta-blockers prevent cardiac rupture after AMI, their effect on serum CRP elevation has not been determined. METHODS: We studied a total of 154 patients with first Q-wave AMI. Patients complicated by pump failure were excluded from this study. Eighty-two patients received beta-blocker treatment within 24 h of the onset of AMI, while 72 patients received no beta-blocker treatment. Peak serum creatine kinase (CK) and CRP levels were determined by serial measurements. RESULTS: There was no difference between the groups according to age, sex, coronary risk factors, pre-infarction angina, infarct site, prior use of cardiovascular drugs, use of revascularization therapy, and prevalence of multivessel disease. Beta-blocker treatment was associated with a lower peak CRP level (6.9 +/- 6.1 vs.10.8 +/- 9.3 mg/dl, p = 0.002), a shorter duration from the onset to the peak CRP level (2 +/- 1 vs. 3 +/- 2 days, p < 0.0001), a lower incidence of cardiac rupture (p = 0.03) and lower in-hospital cardiac mortality (p = 0.02), despite similar peak CK levels. CONCLUSION: The early use of beta-blockers is associated with decreased serum CRP level and a favorable clinical outcome after first Q-wave AMI, suggesting some beneficial effects of beta-blockers on infarct healing after AMI.     

Reversible blindness associated with alcoholic ketoacidosis

PURPOSE: To report a case of reversible blindness associated with severe alcoholic ketoacidosis. DESIGN: Observational case report. METHODS: A 44-year-old male presented with gradual bilateral blindness that developed within a 24-hour period. He suffered from ethanol-induced severe ketoacidosis and shock and was resuscitated with epinephrine and sodium bicarbonate. RESULTS: The treatment of acidosis led to a rapid resolution of the patient's blindness. CONCLUSIONS: It is important to understand the role of severe acidosis as the sole causative factor of reversible bilateral blindness.     

Molecular design of cholesterols as inhibitors of DNA polymerase alpha

The triterpenoid structure is a promising motif for the molecular design of DNA polymerase inhibitors.(1) In this study, 2-(cholesteryloxy)acetic acid (3), 2-(cholestanyl)acetic acid (7), and 2-(stigmasteryl)acetic acid (11) were found to selectively affect only DNA polymerase alpha (pol.alpha). The presence of a carboxyl group at position 28 appears to be essential for the inhibition of the pol.alpha activity. With pol.alpha, these compounds acted by competing with the template-primer DNA and noncompetitively with the substrate.     

Human ATP-binding cassette transporter ABCC10: expression profile and p53-dependent upregulation

Human ATP-binding cassette (ABC) transporter genes are classified into seven sub-families, where "C" subfamily comprises a total of 13 gene members. The ABCC10 cDNA was cloned in the human full-length cDNA project at the Kazusa DNA Research Institute. However, current information is limited regarding its physiological function and gene expression. In the present study, we have investigated the expression of the ABCC10 gene to gain insight into its biological nature. By quantitative PCR, ABCC10 gene expression is demonstrated to be highest in pancreas among the adult and fetal tissues and tumors presently tested. Decreased expression was observed when resting T- and B-cells were activated. Furthermore, when we examined its expression under apoptotic conditions, we found that ABCC10 mRNA levels remarkably increased in doxorubicin-treated MCF7 cells, whereas its up-regulation was suppressed in p53-dominant-negative MCF7 cells. These results suggest that expression of the ABCC10 gene is regulated in a p53-dependent manner during DNA-damage-related apoptosis.     

The genetic polymorphism of drug transporters: functional analysis approaches

Evidence is accumulating to strongly suggest that drug transporters are one of the determining factors governing the pharmacokinetic profile of drugs. To date, a variety of drug transporters have been cloned and classified as solute carriers and ATP-binding cassette transporters. Such drug transporters are expressed in various tissues such as the intestine, brain, liver, and kidney, and play critical roles in the absorption, distribution and excretion of drugs. However, at the present time, information is limited regarding the genetic polymorphism of drug transporters and its impact on their function. In this context, we have undertaken the functional analyses of the polymorphisms identified in drug transporter genes. This article aims to provide an overview on the functional aspects of the non-synonymous polymorphisms of drug transporters and to present standard methods for the evaluation of the effect of polymorphisms on their function.     

Osteosarcomas after the Age of 50: A Clinicopathologic Study of 64 Cases—an Experience in Northern Japan

Background: The clinicopathologic profile and prognostic factors of osteosarcomas after the age of 50 years have been obscure.Methods: Clinicopathologic features were analyzed in 645 patients with osteosarcoma who were registered at the Tohoku Musculoskeletal Tumor Society and National Cancer Center in Tokyo between 1972 and 2002.Results: Sixty-four patients (9.9%; 34 men and 30 women) were more than 50 years old. The most common location was the distal femur (n = 13), followed by the pelvis (n = 10), proximal femur (n = 9), and proximal fibula (n = 6). Seven (11%) patients had lung metastasis at initial presentation. On radiographs, an osteolytic appearance without periosteal reactions was a common and characteristic feature. Forty-eight tumors (75%) were classified as conventional osteosarcomas. Fourteen cases (22%) were secondary; postradiation osteosarcoma was most common in these patients, but there was no Pagets sarcoma. At the initial presentation, misdiagnoses without biopsy were made in 15 (23%) of the 64 cases. Preoperative chemotherapy was given to 22 patients, but the effect was poor in 18 cases (82%). Fifty-four patients underwent surgery, whereas the other 10 patients were treated without surgery because of systemic or inoperable local conditions. The overall survival rate at 5 years was 55.5%. Multivariate analysis showed initial pulmonary metastasis, axial tumor location, and larger tumors as significant prognostic factors.Conclusions: In northern Japan, most patients with osteosarcoma after the age of 50 had primary osteosarcoma. Careful radiological examination and biopsy are mandatory for correct diagnosis. Current systemic chemotherapy is not effective for this age group. Alternative treatment strategies should be considered.     

Association between pentosidine and arteriosclerosis in patients receiving hemodialysis

Background It has been suggested that advanced glycation endproducts (AGEs) accumulate in arteriosclerotic lesions, playing an important role in the development and progression of arteriosclerosis. A chemical quantification method using high-performance liquid chromatography (HPLC) has been established to determine pentosidine levels in these products. Some studies reported that the abdominal aorta calcification index (ACI), obtained by computed tomography (CT), was useful for noninvasively diagnosing arteriosclerosis and determining its severity. In the present study, we measured the ACI and plasma pentosidine in patients receiving maintenance hemodialysis, and investigated the association between arteriosclerosis and pentosidine.Methods In 73 patients receiving maintenance hemodialysis (43 men; 30 women), we determined the ACI, and investigated the association of the ACI with plasma total pentosidine, total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, serum creatinine, and parathyroid hormone (PTH), as well as the product of serum calcium and serum phosphorus, duration of dialysis, and age.Results The ACI did not correlate with total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, serum creatinine, PTH, or the product of serum calcium and serum phosphorus. Age, duration of dialysis, and plasma total pentosidine correlated with the ACI: (y = –33.12 + 0.913x; r = 0.407; P 0.01), (y = 13.94 + 0.403x; r = 0.488; P 0.01), and (y = 14.13 + 0.630x; r = 0.365; P 0.01), respectively.Conclusions It is suggested that pentosidine may be associated with arteriosclerotic development in hemodialysis patients.     

A case of head injury accompanied by minute hemorrhage-like artifacts created by multislice CT scans

We demonstrated a head injury case accompanied by multiple small high-density artifacts in the middle of the brain created by multislice CT scanning, due to the malfunction of a detector involved in reconstruction of the mid images. We named these objects high-density spot artifacts. The high-density spot artifacts resemble minute hemorrhages which appear as diffuse axonal injuries. Radiologists and neurosurgeons should be familiar with this the existence of artifact.