Prognostic Factors in the Surgical Treatment of Ruptured Abdominal Aortic Aneurysms

Although the operative mortality following elective aneurysmectomy has achieved satisfactory results, that following surgery for ruptured abdominal aortic aneurysms (AAAs) remains high. The purpose of this study was to identify the factors affecting the mortality rate associated with the treatment of ruptured AAAs. Between 1978 and 1999, 33 patients underwent emergency surgery for a ruptured AAA. The operative mortality was 33.3% and in-hospital mortality was 6.0%. Hypotension, defined as a systolic blood pressure <80 mmHg, was seen in 19 patients at the time of presentation, 9 of whom underwent surgery in this state. In the remaining 10 patients, it was possible to increase the systolic blood pressure to ≥80 mmHg preoperatively. Of the 11 patients who died within 30 days of surgery, 9 had hypotension at the time of induction of anesthesia and only 2 had a systolic blood pressure of ≥80 mmHg. A satisfactory outcome was achieved in patients whose condition met the following criteria: a systolic blood pressure ≥80 mmHg at the time of operation, minimal aortic cross-clamping time, less blood loss and blood transfusions, and a shorter operation time to repair the ruptured AAA. Concomitant heart disease was also found to be an important prognostic factor. Received: June 16, 1999 / Accepted: March 24, 2000     

Angiogenic effects of adrenomedullin in ischemia and tumor growth

Adrenomedullin (AM) is a novel vasodilating peptide involved in the regulation of circulatory homeostasis and implicated in the pathophysiology of cardiovascular disease. We tested the hypothesis that AM also possesses angiogenic properties. Using laser Doppler perfusion imaging, we found that AM stimulated recovery of blood flow to the affected limb in the mouse hind-limb ischemia model. AM exerted this effect in part by promoting expression of vascular endothelial growth factor (VEGF) in the ischemic limb, and immunostaining for CD31 showed the enhanced flow to reflect increased collateral capillary density. By enhancing tumor angiogenesis, AM also promoted the growth of subcutaneously transplanted sarcoma 180 tumor cells. However, heterozygotic AM knockout mice (AM+/-) showed significantly less blood flow recovery with less collateral capillary development and VEGF expression than their wild-type littermates. Similarly, mice treated with AM22-52, a competitive inhibitor of AM, showed reduced capillary development, and growth of sarcoma 180 tumors was inhibited in AM+/- and AM22-52-treated mice. Notably, administration of VEGF or AM rescued blood flow recovery and capillary formation in AM+/- and AM22-52-treated mice. In cocultures of endothelial cells and fibroblasts, AM enhanced VEGF-induced capillary formation, whereas in cultures of endothelial cells AM enhanced VEGF-induced Akt activation. These results show that AM possesses novel angiogenic properties mediated by its ability to enhance VEGF expression and Akt activity. This may make AM a useful therapeutic tool for relieving ischemia; conversely, inhibitors of AM could be useful for clinical management of tumor growth.     

Epidemiological evidence that acetaldehyde plays a significant role in the development of decreased serum folate concentration and elevated mean corpuscular volume in alcohol drinkers

BACKGROUND: Elevated mean corpuscular volume (MCV) is a traditional biological marker for alcohol abuse and alcoholism, but the underlying mechanism is unclear. Three recent epidemiologic studies consistently showed that MCV was elevated by alcohol drinking more markedly among individuals with genetically inactive aldehyde dehydrogenase-2 (ALDH2) (encoded by ALDH2*2 mutant allele) than those with active ALDH2 (encoded by ALDH2*1/2*1 genotype), suggesting that the elevated MCV was etiologically linked to acetaldehyde exposure. The purpose of the present study was to clarify further this relationship by examining the status of folate and vitamin B12. METHODS: The study participants were 159 men who were aged 40 to 69 years and randomly selected from a Japanese rural population. The genetic polymorphism of ALDH2 was determined by PCR-restriction fragment length polymorphism method; data on alcohol drinking and other lifestyles were collected using a structured questionnaire; serum concentrations of folate and vitamin B12 were measured using the protein competitive reaction method, and blood cell counts were measured by routine methods. A multiple linear regression model was used to analyze the data. RESULTS:: The relationship between alcohol drinking and serum folate concentration was significantly different between ALDH2 genotypes, indicating that the reduction of serum folate by alcohol drinking was more marked in men with ALDH2*1/2*2 than those with ALDH2*1/2*1. The relationship between alcohol drinking and elevated MCV was significantly stronger in men with ALDH2*1/2*2 than those with ALDH2*1/2*1 even after adjustment for serum folate and vitamin B12 concentrations. CONCLUSIONS: These findings indicate that acetaldehyde plays a significant role in the development of decreased serum folate concentration and elevated MCV by alcohol drinking.     

Morphometric investigation of the hippocampal formation in Ihara's genetically epileptic rats using magnetic resonance images and histopathology

The newly developed Ihara's genetically epileptic rat (IGER) is thought to be a useful tool for studying epilepsy of the limbic type. Morphological changes in the hip-pocampus, which is one of the characteristic findings in the brains of patients with temporal lobe epilepsy, were presumed to occur also in IGER during the course of epileptic activities. We investigated chronological changes in volume of the IGER hippocampal formation using mag-netic resonance (MR) imaging. The experiment consisted of two protocols. First, MR imaging was performed for volumetric measurement of the cerebrum and the hippocampus in four male IGER, each at 2, 4, 6, 8, 10 and 12 months of age. After MR examination, the brains were subjected to histological and morphometric examinations. Second, changes in the hippocampal volume were traced chronologically in three IGER at the ages of 2, 4, 6, 8 and 10 months. Age-matched Wistar rats were used as controls. In IGER, the volume of the cerebrum, especially of the hippocampus, and the ratio of the hippocampal to the cerebral volume increased, in concert with the increase in seizure activities. Histological and morphometric invest-igations revealed that there was mild astrogliosis and marked microgliosis with hypertrophic change in the hippocampal formation with aging, but no loss of neurons was observed. Neither an increase in volume nor gliosis was found in the brains of control rats. The enlargement of the hippocampal formation in IGER brains was assumed to be partially due to gliosis of astrocyte and microglia with hypertrophy.     

Psychiatric Patients Showing Irregular β Activities in EEGs and Treatment with Antiepileptic Drugs: A Report of 15 Cases†

Abstract: Fifteen psychiatric cases are reported who were clinically diagnosed as schizophrenic, affective disorders, or neurotic, but resisted standard medication regimens, all showing irregular β activities on EEGs. The cases tended to display symptoms in common, such as dysphoria, emotional instability or frequent physical complaints. These characteristic symptoms share something mutually with the symptoms shown in some epileptic patients or psychiatric patients with epileptic EEG abnormalities without clinical seizures. Antiepileptic drugs seemed more specifically effective to the above symptoms. More than half of these cases showed improvement on EEG findings such as a decrease in irregular β activities and an increase in rhythmicity or regularity of α activities along with clinical improvement with the administration of adjunctive antiepileptic drugs. These results suggest that the adjunctive administration of antiepileptic drugs to patients with irregular β activities on EEGs is clinically useful and an EEG examination has much value in psychiatric practice to find the criteria of drug therapy.     

Antithrombin reduces the ischemia/reperfusion-induced spinal cord injury in rats by attenuating inflammatory responses

Antithrombin (AT) reveals its antiinflammatory activity by promoting endothelial release of prostacyclin (PGI(2)) in vivo. Since neuroinflammation is critically involved in the development of ischemia/reperfusion (I/R)-induced spinal cord injury (SCI), it is possible that AT reduces the I/R-induced SCI by attenuating the inflammatory responses. We examined this possibility using rat model of I/R-induced SCI in the present study. AT significantly reduced the mortality and motor disturbances by inhibiting reduction of the number of motor neurons in animals subjected to SCI. Microinfarctions of the spinal cord seen after reperfusion were markedly reduced by AT. AT significantly enhanced the I/R-induced increases in spinal cord tissue levels of 6-keto-PGFIalpha, a stable metabolite of PGI2. AT significantly inhibited the I/R-induced increases in spinal cord tissue levels of TNF-alpha, rat interleukin-8 and myeloperoxidase. In contrast,Trp(49) -modified AT did not show any protective effects. Pretreatment with indomethacin significantly reversed the protective effects of AT. An inactive derivative of factor Xa, which selectively inhibits thrombin generation, has been shown to fail to reduce SCI.Taken together, these observations strongly suggested that AT might reduce I/R-induced SCI mainly by the antiinflammatory effect through promotion of endothelial production of PGI(2). These findings also suggested that AT might be a potential neuroprotective agent.     

Functional fitness gain varies in older adults depending on exercise mode

Various exercise modes are available to improve functional fitness (FF) in older adults. However, information on the comparative capability of different exercise modes to improve FF is insufficient. PURPOSE: To compare the effects of aerobic, resistance, flexibility, balance, and Tai Chi programs on FF in Japanese older adults. METHODS: FF was evaluated using a chair stand, arm curl, up and go, sit and reach, back scratch, functional reach, and 12-min walk. One hundred thirteen older adults (73 +/- 6 yr, 64 men, 49 women) volunteered for one of five exercise groups: aerobic (AER), resistance (RES), balance (BAL), flexibility (FLEX), and Tai Chi (T-CHI), or they were assigned to the wait-list control group (CON). Programs were performed for 12 wk, 2 d x wk(-1) (RES, BAL, FLEX, T-CHI) or 3 d x wk(-1) (AER), and 90 min x d(-1). RESULTS: Improvement in cardiorespiratory fitness was limited to AER (16%). Improvements in upper- and lower-body strength and balance/agility were outcomes of RES, BAL, and T-CHI. RES elicited the greatest upper-body strength improvement (31%), whereas BAL produced the greatest improvement in lower-body strength (40%). Improvements in balance/agility were similar across RES (10%), BAL (10%), and T-CHI (10%). Functional reach improved similarly in AER (13%), BAL (16%), and RES (15%). There were no improvements in flexibility. CONCLUSION: Results suggest that a single mode with crossover effects could address multiple components of fitness. Therefore, a well-rounded exercise program may only need to consist of two types of exercise to improve the components of functional fitness. One type should be aerobic exercise, and the second type could be chosen from RES, BAL, and T-CHI.