Coronary artery bypass grafting in octogenarians

Preoperative profiles, postoperative complications, and the early and late results in 32 patients 80 yrs. of age and older (elderly group) who underwent coronary artery bypass grafting were compared with those in patients under 80 yrs. of age (control group). In the elderly group, the prevalence of patients with preoperative creatinine clearance (Ccr.) <50 l/day (34.4%), unstable angina pectoris (78.1%) and left main trunk disease (40.1%) was significantly higher than those in the control group. The incidences of arrhythmia and intensive care unit(ICU) syndrome were also significantly higher in the elderly group than in the control group, however, there was no death due to these complications. In the elderly group, one patient (3.1%) died in the hospital due to low cardiac output syndrome (LOS), while three patients (2.4%) of the control group died in the hospital. As for the long-term results, the 5-yr. survival rates for the elderly group and the control group were 82.6% and 85.2%, respectively, and the effectiveness of surgery was remarkable, with improved postoperative activity in 96.9% of the elderly group. These findings indicate that although the elderly patients have higher risks by undergoing surgery and have a disadvantage in the rate of postoperative complications, the postoperative improvement in activity and survival rate can be similar to those in the younger patients.     

B-type natriuretic peptide after hormone therapy in postmenopausal women with chest pain and normal coronary angiogram

OBJECTIVES: Coronary heart disease is relatively uncommon in premenopausal women but shows a sharp increase after menopause. The decline of endogenous ovarian hormones is commonly assumed to be a major component of this phenomenon. The effects of estrogens on the vasculature have been investigated extensively in previous studies. However, the effects of estrogens on myocardial function have not been evaluated in humans. We sought to examine the effects of hormone therapy (HT) on myocardial function and cardiac natriuretic peptides in postmenopausal women with chest pain and a normal coronary angiogram. DESIGN: Transdermal HT (estradiol: 0.72 mg/2 d) was administered to 15 postmenopausal women with chest pain and a normal coronary angiogram (mean age, 53 y) for 12 weeks, and oral HT (conjugated equine estrogens: 0.625 mg/d) was administered to another 15 postmenopausal women (mean age, 54 y) for 12 weeks. Echocardiography or cardiac catheterization showed no cardiac dysfunction in any woman at baseline. Cardiac function was evaluated by echocardiography, and plasma B-type natriuretic peptide was measured every 4 weeks. RESULTS: B-type natriuretic peptide levels increased after transdermal HT (baseline: 13.1 +/- 3.1, 4 wk: 22.1 +/- 2.9, 8 wk: 33.2 +/- 3.1, 12 wk: 38.4 +/- 3.3 pg/mL; P < 0.01 vs baseline). The levels were also augmented after oral HT (baseline: 14.1 +/- 3.8, 4 wk: 23.2 +/- 3.3, 8 wk: 35.6 +/- 3.9, 12 wk: 39.6 +/- 3.5 pg/mL; P < 0.01 vs baseline). Serial echocardiography showed no changes in ventricular function in either treatment group. At baseline the serum estradiol levels in the transdermal group were comparable with those in the oral group. CONCLUSIONS: The estradiol levels after HT increased in both groups, but there was no significant difference between the two groups. B-type natriuretic peptide levels increased without cardiac dysfunction, and the chest symptoms were relieved in some participants after HT. Thus, estrogen supplementation augments natriuretic peptide levels without harmful effects on ventricular function.     

Major structural polypeptides of retrovirus produced by a Suncus murinus mammary tumor cell line and type D retrovirus share interspecies antigenic determinants

Constitutive polypeptides of retrovirus produced by a Suncus murinus mammary tumor cell line (Sm-MTV) were characterized by immunofluorescence and immunoblotting. The major structural polypeptide of Sm-MTV, molecular weight 44/43K, immunologically cross reacted with the structural polypeptides of Mason-Pfizer monkey virus (MPMV) (molecular weights 27K and 12/10K). Sm-MTV constitutive polypeptides did not show antigenic relatedness with those of the following mammalian retroviruses: murine mammary tumor virus, Rausher murine leukemia virus, Molony murine leukemia virus, Osborn-Mendel rat leukemia virus, feline leukemia virus, RD114 virus, simian sarcoma virus 1, and human T-cell leukemia virus type I. Among the Sm-MTV structural polypeptides, those with molecular weights of 72/69K and 47K were glycosylated.     

Significance of the serum level of soluble E-cadherin in patients with HCC

BACKGROUND/AIMS: E-cadherin (E-cad) is a type of adhesion molecule, and recent studies have demonstrated a correlation between its expression in tumor lesions and the recurrence of HCC. Serum levels of soluble E-cad are significantly elevated in patients with several types of cancer. The authors evaluated the significance of the serum level of soluble E-cad as a predictor of early recurrences (intrahepatic or extrahepatic metastasis) of HCC after a curative resection. METHODOLOGY: The concentrations of soluble E-cad in the serum of 25 HCC patients before surgery and 12 healthy subjects were measured using a sandwich enzyme-linked immunosorbent assay. The hepatic expression of E-cad was examined by immunohistochemical staining. RESULTS: The median serum soluble E-cad levels were significantly elevated in HCC patients before surgery in comparison to those in healthy subjects (10,759 ng/mL vs. 5,798 ng/mL, p < 0.05). The patients in the high serum soluble E-cad group experienced a higher incidence of early recurrence (p < 0.05). The levels of expression of E-cad in HCC lesions were not related to the serum levels of soluble E-cadherin. CONCLUSIONS: The study demonstrated that serum soluble E-cad levels were elevated in patients with HCC, and high serum soluble E-cadherin (> or = 8,000 ng/ml) was associated with early recurrence or extrahepatic metastasis. Serum soluble E-cad may therefore be a potential prognostic marker for HCC.     

Feasibility of Using an Enzymatically Activatable Fluorescence Probe for the Rapid Evaluation of Pancreatic Tissue Obtained Using Endoscopic Ultrasound-Guided Fine Needle Aspiration: a Pilot Study

Purpose

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the most reliable method for the histological diagnosis of pancreatic tumors. Rapid on-site fluorescence-guided histological diagnosis was evaluated by topically applying an enzymatically activatable probe onto the EUS-FNA samples; the probe fluoresces in the presence of γ-glutamyltranspeptidase (GGT).

Procedures

We evaluated GGT expression in pancreatic cancer cell lines in vitro. EUS-FNA was performed in 10 pancreatic tumors. After topical application of the probe, signal intensity was measured using a fluorescence imaging system for 13 min.

Results

GGT was expressed in Panc-1, AsPC-1, and AR42J, but not in KP4 cells. In samples from six cases, several regions of the specimens fluoresced and contained adequate tissue for pathological diagnosis. The remaining four non-fluorescent samples contained very small amounts of carcinoma, normal epithelial cells, or no epithelial cells. The signal intensity at 5 min was 25.5?±?7.7 and 7.7?±?0.5 in fluorescent and non-fluorescent regions, respectively (p?<?0.05).

Conclusions

Application of enzymatically activatable probe onto EUS-FNA samples would be feasible for the rapid evaluation of tissues suitable for histological diagnosis.

     

Possible involvement of a cell adhesion molecule,Migfilin, in brain development and pathogenesis of autism spectrum disorders

Migfilin, encoded by FBLIM1 at the 1p36 locus, is a multi‐domain adaptor protein essential for various cellular processes such as cell morphology and migration. Small deletions and duplications at the 1p36 locus, monosomy of which results in neurodevelopmental disorders and multiple congenital anomalies, have also been identified in patients with autism spectrum disorder (ASD). However, the impact of FBLIM1, the gene within 1p36, on the pathogenesis of ASD is unknown. In this study, we performed morphological analyses of migfilin to elucidate its role in brain development. Migfilin was detected specifically in the embryonic and perinatal stages of the mouse brain. Either silencing or overexpression of migfilin in embryos following in utero electroporation disrupted Neocortical neuronal migration. Additionally, neurite elongation was impaired when migfilin was silenced in cultured mouse hippocampal neurons. We then screened FBLIM1 for rare exonic deletions/duplications in 549 Japanese ASD patients and 824 controls, detecting one case of ASD and intellectual delay that harbored a 26‐kb deletion at 1p36.21 that solely included the C‐terminal exon of FBLIM1. The FBLIM1 mRNA expression level in this case was reduced compared to levels in individuals without FBLIM1 deletion. Our findings indicate that tightly regulated expression of migfilin is essential for neuronal development and that FBLIM1 disruption may be related to the phenotypes associated with ASD and related neurodevelopmental disorders.     

Rapid cancer detection by topically spraying a γ-glutamyltranspeptidase-activated fluorescent probe

The ability of the unaided human eye to detect small cancer foci or accurate borders between cancer and normal tissue during surgery or endoscopy is limited. Fluorescent probes are useful for enhancing visualization of small tumors but are typically limited by either high background signal or the requirement for administration hours to days before use. We synthesized a rapidly activatable, cancer-selective fluorescence imaging probe, γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), with intramolecular spirocyclic caging for complete quenching. Activation occurs by rapid one-step cleavage of glutamate with γ-glutamyltranspeptidase (GGT), which is not expressed in normal tissue, but is overexpressed on the cell membrane of various cancer cells, thus leading to complete uncaging and dequenching of the fluorescence probe. In vitro activation of gGlu-HMRG was evident in 11 human ovarian cancer cell lines tested. In vivo in mouse models of disseminated human peritoneal ovarian cancer, activation of gGlu-HMRG occurred within 1 min of topically spraying the tumor, creating high signal contrast between the tumor and the background. The gGlu-HMRG probe is practical for clinical application during surgical or endoscopic procedures because of its rapid and strong activation upon contact with GGT on the surface of cancer cells.     

Combination of ADH1B*2/ALDH2*2 polymorphisms alters acetaldehyde-derived DNA damage in the blood of Japanese alcoholics

The acetaldehyde associated with alcoholic beverages is an evident carcinogen for the esophagus. Genetic polymorphisms of the alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) genes are associated with the risk of esophageal cancer. However, the exact mechanism via which these genetic polymorphisms affect esophageal carcinogenesis has not been elucidated. ADH1B*2 is involved in overproduction of acetaldehyde due to increased ethanol metabolism into acetaldehyde, and ALDH2*2 is involved in accumulation of acetaldehyde due to the deficiency of acetaldehyde metabolism. Acetaldehyde can interact with DNA and form DNA adducts, resulting in DNA damage. N²‐ethylidene‐2′‐deoxyguanosine (N²‐ethylidene‐dG) is the most abundant DNA adduct derived from acetaldehyde. Therefore, we quantified N²‐ethylidene‐dG levels in blood samples from 66 Japanese alcoholic patients using liquid chromatography/electrospray tandem mass spectrometry, and investigated the relationship between N²‐ethylidene‐dG levels and ADH1B and ALDH2 genotypes. The median N²‐ethylidene‐dG levels (25th percentile, 75th percentile) in patients with ADH1B*1/*1 plus ALDH2*1/*1, ADH1B*2 carrier plus ALDH2*1/*1, ADH1B*1/*1 plus ALDH2*1/*2, and ADH1B*2 carrier plus ALDH2*1/*2 were 2.14 (0.97, 2.37)/10⁷ bases, 2.38 (1.18, 2.98)/10⁷ bases, 5.38 (3.19, 6.52)/10⁷ bases, and 21.04 (12.75, 34.80)/10⁷ bases, respectively. In the ALDH2*1/*2 group, N²‐ethylidene‐dG levels were significantly higher in ADH1B*2 carriers than in the ADH1B*1/*1 group (P < 0.01). N²‐ethylidene‐dG levels were significantly higher in the ALDH2*1/*2 group than in the ALDH2*1/*1 group, regardless of ADH1B genotype (ADH1B*1/*1, P < 0.05; ADH1B*2 carriers, P < 0.01) N²‐ethylidene‐dG levels in blood DNA of the alcoholics was remarkably higher in individuals with a combination of the ADH1B*2 and ALDH2*2 alleles. These results provide a new perspective on the carcinogenicity of the acetaldehyde associated with alcoholic beverages, from the aspect of DNA damage.     

Psychotherapy, symptom outcomes, and role functioning over one year among patients with bipolar disorder

OBJECTIVE: Randomized trials indicate that psychosocial interventions effective adjuncts to pharmacotherapy in bipolar disorder (1,2). A one-year naturalistic-prospective design was used to examine the association between psychotherapy use and the symptomatic and functional outcomes of patients with bipolar disorder. METHODS: Patients with bipolar disorder in a depressed phase (N=248) were drawn from the first 1,000 enrollees (November 1999 to April 2002) in the Systematic Treatment Enhancement Program (STEP-BD), a study of patients with bipolar disorder receiving best-practice pharmacotherapy. Patients were seen clinics and interviewed every three months over one year regarding of psychotherapy services, symptoms, and role functioning. Mixed-effects regression models were used to examine whether the amount of psychotherapy the patients received during each three-month interval was associated with symptomatic or psychosocial functioning during the same or a subsequent three-month interval. RESULTS: During the study year, percent of the patients had at least one psychotherapy session. Among patients who began an interval with severe depressive symptoms or low functioning, having more frequent sessions of psychotherapy was associated with less severe mood symptoms and better functioning in the same or a subsequent study interval. In contrast, among patients who began interval with less severe depressive symptoms or higher functioning, fewer psychotherapy sessions were associated with less severe depressive symptoms and greater functioning in the same or a subsequent interval. CONCLUSIONS: Intensive psychotherapy may be most applicable to severely ill patients with bipolar disorder, whereas briefer treatments may be adequate for less severely ill patients.