Differences in atherosclerotic profiles between patients with thoracic and abdominal aortic aneurysms

Differences in atherosclerotic profiles between patients with thoracic aortic aneurysm (TAA) and patients with abdominal aortic aneurysm (AAA) have not been studied. We retrospectively studied the clinical records of 343 consecutive patients (132 TAA and 211 AAA) who were admitted to our hospital for elective repair of aortic aneurysms between July 2001 and December 2004. Clinical variables were compared between patients with TAA and those with AAA by using a univariate analysis, and those achieving statistical significance were subsequently assessed in a multivariate analysis. The incidence of coronary artery disease (CAD) (53% vs 23%, p <0.0001), 3-vessel coronary disease (41% vs 10%, p <0.0001), male gender (86% vs 74%, p <0.01), smoker (88% vs 76%, p <0.01), chronic obstructive pulmonary disease (COPD) (30% vs 15%, p <0.01), and diabetes mellitus (39% vs 23%, p <0.01) were significantly higher in patients with AAA than in those with TAA. In contrast, the incidence of hypertension (91% vs 81%, p <0.05), saccular-type aneurysm (61% vs 7%, p <0.0001), and body mass index (24.1 +/- 3.1 vs 23.2 +/- 3.5, p <0.05) were significantly higher in patients with TAA than in those with AAA. Multivariate stepwise logistic analysis revealed that CAD (odds ratio [OR] 3.65; 95% confidence interval [CI] 2.12 to 6.42; p <0.0001), COPD (OR 2.05; 95% CI 1.11 to 3.89; p <0.05), and diabetes mellitus (OR 1.85; 95% CI 1.06 to 3.27; p <0.05) were associated with AAA, and that body mass index (OR 9.39; 95% CI 2.0 to 46.8; p <0.01), hypertension (OR 3.09; 95% CI 1.48 to 6.87; p <0.01), and cerebral infarction (OR 2.83; 95% CI 1.25 to 6.50; p <0.05) were associated with TAA. In conclusion, atherosclerotic profiles are significantly different between patients with TAA and patients with AAA. This result suggests the possibility that mechanisms underlying the development of aortic aneurysms may differ between TAA and AAA, and, from the perspective of prevention, provides further stimulus for the modification of key risk factors for atherosclerosis.     

Altered relationship between body fat and plasma adiponectin in end-stage renal disease

Patients with end-stage renal disease (ESRD) show an inverse association between body mass index and risk of death from cardiovascular disease. Paradoxical epidemiology may suggest some beneficial effects of body fat in ESRD. Because an antiatherogenic adipocytokine adiponectin is increased in uremic plasma, we tested a hypothesis that, in ESRD, plasma adipocytokine profile may be less atherogenic or that the relationship between body fat and adipocytokines may be altered. The subjects were 103 patients with ESRD undergoing hemodialysis and 166 healthy subjects comparable in age and sex. We measured body fat mass by dual-energy x-ray absorptiometry and plasma levels of adiponectin and leptin by enzyme-linked immunosorbent assay. The ESRD group showed a significant increase in plasma adiponectin, leptin, and adiponectin/leptin ratio than the healthy subjects. Although sex and fat mass were significant factors correlating with plasma adiponectin level in the healthy group, none of these were significantly associated with plasma adiponectin in the patients with ESRD. In contrast, leptin showed significant relationships with sex and fat mass regardless of the presence of ESRD. Plasma adiponectin correlated negatively with plasma triglycerides and positively with high-density lipoprotein cholesterol in both healthy and ESRD groups, suggesting that uremic adiponectin retains its actions in favor of its antiatherogenicity. Thus, plasma adipocytokine profile was altered in ESRD, and the effects of body fat and sex on adiponectin were less significant in the patients with ESRD.     

Programmable cells: interfacing natural and engineered gene networks

Novel cellular behaviors and characteristics can be obtained by coupling engineered gene networks to the cell's natural regulatory circuitry through appropriately designed input and output interfaces. Here, we demonstrate how an engineered genetic circuit can be used to construct cells that respond to biological signals in a predetermined and programmable fashion. We employ a modular design strategy to create Escherichia coli strains where a genetic toggle switch is interfaced with: (i) the SOS signaling pathway responding to DNA damage, and (ii) a transgenic quorum sensing signaling pathway from Vibrio fischeri. The genetic toggle switch endows these strains with binary response dynamics and an epigenetic inheritance that supports a persistent phenotypic alteration in response to transient signals. These features are exploited to engineer cells that form biofilms in response to DNA-damaging agents and cells that activate protein synthesis when the cell population reaches a critical density. Our work represents a step toward the development of "plug-and-play" genetic circuitry that can be used to create cells with programmable behaviors.     

Perioperative management of benign hepatic tumors in patients with glycogen storage disease type Ia

Glycogen storage disease type Ia (GSD-Ia; von Gierke disease) is an inherited disorder caused by glucose-6-phosphatase deficiency, and there have been some reports of hepatic tumors in patients with this disease. We report two patients with benign hepatic tumors with GSD-Ia. One is a 19-year-old man who underwent segmentectomy 4 for a focal nodular hyperplasia, and the other is a 31-year-old woman who underwent segmentectomies 3, 5, and 6 for hepatic adenomas. Two significant perioperative complications, resulting from the carbohydrate metabolic disorders, hypoglycemia and metabolic acidosis, occurred in both patients. We managed the metabolic complications successfully by administering a sufficient volume of glucose intravenously. Close perioperative monitoring of blood glucose and lactate concentrations is essential in the perioperative management of patients with GSD-Ia. The intravenous administration of glucose, starting with a smaller dose and then increasing the dose, is adequate management for lactic acidosis with or without hypoglycemia during the perioperative period.     

Relationship between acute rejection and cyclosporine or mycophenolic acid levels in Japanese heart transplantation.

BACKGROUND: Cyclosporine (CsA), Mycophenolate mofetil (MMF) and prednisolone (PSL) are widely used for the prevention of acute rejection after heart transplantation. Recently, the serum concentration - time curves (AUC) of CsA and MMF have been demonstrated to be precise predictors of acute rejection. METHODS AND RESULTS: Fourteen heart transplant patients were treated concomitantly with CsA, MMF, and PSL between May 1999 and November 2005 at the National Cardiovascular Center and of them 3 had acute rejection episodes [International Society for Heart & Lung Transplantation grade 3a]. Two patients (man in his 30 s; woman in her 40 s) had acute rejection with a mycophenolic acid (MPA) AUC(0-12 h) <30 microg x h x ml(-1) and low CsA AUC (AUC(0-4 h); 2,408 ng x h x ml-1, 1,735 ng x h x ml-1). However, 1 patient (man in his 30 s) with a high CsA AUC(0-4 h) (4,019 ng x h x ml-1) did not develop cardiac allograft rejection even if the MMF was temporarily stopped. These 3 patients were investigated to evaluate the relationship between acute rejection and pharmacokinetic parameters, including the CsA C0, C2, AUC(0-4 h) and MPA AUC(0-12 h). CONCLUSIONS: The findings suggest that a high CsA AUC(0-4 h) may prevent rejection of a cardiac allograft, even if MMF is stopped or drastically reduced.     

Use of serum insulin-like growth factor-I levels to predict psychiatric non-response to donepezil in patients with Alzheimer's disease.

OBJECTIVE: Insulin-like growth factor-I (IGF-I) deficiency may be involved in cognitive deficits seen with aging and in neurodegenerative diseases such as Alzheimer's disease (AD). This study was aimed at investigating whether non-responder to donepezil could be predicted using decreased serum levels of IGF-I in AD patients. DESIGN: This study involved 106 elderly subjects: 50 patients with AD and 56 age-matched controls without dementia. In patients with AD, donepezil was given orally 3 mg/day for 4 weeks and 5 mg/day for another 12 weeks. AD patients were divided into responders and non-responders based on the changes in mini-mental state examination (MMSE) scores before and 16 weeks after treatment with donepezil. Serum levels of IGF-I and atherogenic biomarkers were determined. RESULTS: Before treatment with donepezil, there was a significant positive correlation between serum IGF-I levels and the MMSE scores in all subjects. Serum IGF-I levels and the MMSE scores were significantly lower in AD patients than in non-demented controls and were the lowest in non-responders to donepezil. Atherogenic biomarkers (LDL cholesterol, triglycerides, lipoprotein(a), lipid peroxide, apolipoprotein E, and glucose levels) did not differ significantly among these groups. On multiple logistic regression, non-responders to donepezil showed decreased serum IGF-I levels <110 ng/ml and MMSE scores <15 points before treatment. CONCLUSIONS: These findings suggest that decreased levels of serum IGF-I combined with MMSE scores before treatment could predict non-responders to donepezil among AD patients, which may be a simple and practical method for selecting patients expected to show a response to treatment.     

Mechanism of inhibitory effect of glucagon on gastrointestinal motility and cause of side effects of glucagon

Glucagon is commonly used during gastrointestinal examinations for the temporary inhibition of gastroduodenal movements. Three preparations of glucagon are now clinically available: those prepared by extraction from the pancreas (GL-P), by chemical synthesis (GL-S), and by genetic recombination (GL-G). The aim of this study was examine the mechanism of the inhibitory effect of glucagon on gastrointestinal motility and the cause of its side effects by comparing three glucagon preparations. In four conscious dogs, gastrointestinal contractions were monitored by means of chronically implanted force transducers. Each glucagon preparation (GL-P [15 μg/kg], GL-S [5, 15, 45 μg/kg], GL-G [15 μg/kg]), scopolamine butylbromide (0.4 mg/kg), or saline was administered intravenously 20 min after the termination of spontaneous phase III contractions, and blood samples were taken at 5- to 10-min intervals. Barium was administered into the stomach 10 min after the infusion of each drug. The arrival of a barium meal in the stomach immediately stimulated gastrointestinal contractions, and the barium meal was expelled into the duodenum and jejunum from the stomach. Intravenous injection of 15 μg GL-S first stimulated duodenal contractions that propagated to the jejunum, followed by strong inhibition of the barium-induced gastrointestinal contractions. This inhibitory effect of glucagon and the activity of the glucagon-induced duodenal contractions were dose-related. The inhibitory effects of GL-G and GL-S were stronger than that of GL-P. Blood glucose and plasma insulin concentrations were raised after intravenous injection of each glucagon preparation, but there was no difference among the three preparations and no dose relationship. The inhibitory effects of glucagon depend on the material purity and dose, and the inhibitory mechanism was independent of any effect on carbohydrate metabolism. Glucagon administration caused phase III-like contractions in the duodenum and jejunum, which may be responsible for the side effects of glucagon. (Received Jan. 8, 1998; accepted June 26, 1998)     

Intraperitoneal exfoliated cancer cells in patients with colorectal cancer

PURPOSE: The aims of this study were to evaluate potential predictors of exfoliated free cancer cells in the peritoneal cavity and to assess intraoperative peritoneal lavage cytology as a prognostic indicator in patients with colorectal cancer. METHODS: From 1985 to 1987, intraoperative peritoneal lavage cytology was performed in 140 patients with colorectal cancer. Among them, 88 patients underwent curative resection and 52 patients had noncurative surgery. Cytology was examined twice,i.e., immediately after opening the peritoneal cavity (precytology) and just before closing the abdomen (postcytology). One hundred milliliters of saline was poured into the peritoneal cavity and it was retrieved by suction after irrigation. Cytologic examination was performed after staining with Papanicolaou, Giemsa, periodic acid-Schiff, and Alcian blue stains. RESULTS: Among the 140 patients examined, the incidence of positive cytology in the prelavage was 15 percent, and that in the postlavage was 9 percent, although it was 16 percent in either lavage. Among patients with curative resection, 10 percent had positive cytology. Seven characteristics were identified as features of tumors which are prone to exfoliate cells into the peritoneal cavity: 1) macroscopic peritoneal dissemination, 2) liver metastasis, 3) more than 20 ml of ascites, 4) ulcerated tumors without definite borders, 5) invasion of the serosal surface or beyond, 6) semiannular or annular shape, and 7) moderate or marked lymphatic invasion. In patients undergoing curative surgery, among these features, circumferential involvement was the only one correlated closely with positive cytology (P<0.02). Positive cytology was associated with a worse outcome. In patients who were resected curatively, the postcytology had a stronger influence on local recurrence than the precytology; the local recurrence rate in patients with positive postcytology was higher than in those with negative postcytology, regardless of the precytology. All patients with cancer cells in the peritoneal cavity at the end of surgery had recurrence. CONCLUSIONS: Seven characteristics were identified as risk factors for exfoliation of cancer cells into the peritoneal cavity in patients with colorectal cancer. These findings may be helpful for the choice of laparoscopic surgery in this era of increasing port-site metastases after laparoscopic procedure. The results of peritoneal lavage cytology at the end of surgery were correlated with the long-term postoperative outcome of colorectal cancer. Thus, meticulous follow-up and possibly adjuvant chemotherapy may be beneficial for patients with free cancer cells in lavage fluid, even after curative surgery.