Epidemiological features and diagnostic evaluation of intracranial aneurysms

Female gender and cigarette smoking appear to be risk factors for the development of multiple intracranial aneurysms. An acquired nature is likely in this form. The mechanism of aneurysm formation in patients with sickle cell anemia is apparently different. These patients also present multiple aneurysms that show propensity for vertebrobasilar territory and appear at a younger age. Familial cerebral aneurysms are diagnosed once heritable connective tissue disorders have been excluded. The age of patients tends to be lower and the size of aneurysm to be smaller at the time of rupture in the familial form. These aneurysms are less frequently found in the anterior communicating artery than the sporadic aneurysms. A high incidence of asymptomatic familial aneurysms was detected in people with family histories of intracranial aneurysms studied by means of magnetic resonance angiography. Furthermore, familial aneurysms are more likely to rupture in families having members with aneurysmal subarachnoid hemorrhage (SAH) than in those without. The results of an interesting study using color "power" transcranial Doppler ultrasound in patients with aneurysmal SAH suggest that as the intracranial pressure diminished, the size of the aneurysm increased, and there was relatively little change between maximum and minimum dimensions during the cardiac cycle, i.e., the pulsatility is reduced. The use of postoperative angiography after clipping is a matter of debate. The indication more widely accepted is in large aneurysms with a wide neck, in which incomplete clipping can be suspected. Taking into account the current low risk of angiography in centers of excellence, its routine use may be recommended. Aneurysm remnants, vessel occlusion, vasospasm, and newly identified aneurysms are the main findings that were reported.     

Early diagnosis of Alzheimer dementia based on clinical and biological factors

Alzheimer’s disease (AD) is common in elderly individuals; it causes distress for the patients and their relatives as well as large costs for the society. With the advent of symptomatic treatment at present and probable etiology-based cures in the future, it will be possible to relieve and put an end to these negative effects. Therefore, it is necessary to diagnose the disease as early as possible. In this review, we briefly summarize the state-of-the-art concerning various available clinical and biochemical methods for identifying AD. Increasing age, heritage, and presence of ApoE e4 allele have been confirmed as risk factors for AD as well as some putative factors (e.g., low education, hypertension, hypotension) based on epidemiological recent research. Selective impairment of episodic memory has been found to be a preclinical marker for future development of AD based on convergent data from asymptomatic AD-related mutation carriers, longitudinal studies of patients with mild cognitive impairment (MCI), and epidemiological studies of incident AD cases. Neurophysiological methods are inexpensive and useful for the identification of changes in brain dysfunction in AD and new promising methods are under development. Using magnetic resonance imaging (MRT), structural measurements of brain atrophy and specific brain structures such as the hippocampus have been reported to detect dementia development early in the course of disease. Similarly, functional measurements of brain activity (e.g., blood flow) have revealed that hypometabolism in bilateral parietotemporal brain areas early in the disease course. Finally, biochemical studies have demonstrated that certain proteins (e.g., tau the Aβ_1-42/43 metabolite of the amyloid precursor protein) may be associated with the disease process in AD, although the specificity of these markers remains to be established. It is concluded that still no single marker of AD exists, which makes it necessary to rely on data from multiple sources in order to arrive at the best possible diagnosis of AD.     

Origin of the "N10" stationary-field potential after median nerve stimulation.

The scalp far-field potentials after median nerve stimulation at the wrist consist of P9, P11, P13, and P14 positive components. Earlier, Emerson et al. (1984) identified the "N10" negative potential in-between the P9 and P11 and claimed that this was not merely a passive return to the baseline after the P9 positive deflection but a distinct component reflecting a proximal brachial plexus volley. They thought N10 was a far-field potential having widespread distribution with a fixed latency. In this study we found that N10 was of higher amplitude after median nerve stimulation at the elbow than after stimulation at the wrist. Indeed the N10 latency was fixed from the lower anterior neck to the scalp, and its amplitude was maximum at the anterior lower neck. The latency of N10 was about 0.3 milliseconds longer than the Erb's potential and 0.15 milliseconds longer than the potential recorded from the lateral neck on the side of stimulation. The N10 amplitude increased in parallel with increased stimulus intensity. In order to explore the origin of the N10 stationary field potential, we designed a paired stimuli paradigm applied to the wrist (S1) and to the elbow (S2). The interstimulus interval between S and S2 was adjusted so that the timing of S2 was immediately after the traveling impulse produced by the S1 stimulus as it passed through the S2 stimulus site. This technique allowed stimulation of the anterior interosseous nerve selectively at the elbow while the median nerve originating from the wrist was undergoing refractory period. The response of (S1 + S2) - S1 showed only the N10 with absence of cervical and cortical responses, implying that N10 was activated, predominantly by the interosseous nerve, i.e., an antidromic motor volley, when the median nerve was stimulated at the elbow.     

Impact of graft size mismatching on graft prognosis in liver transplantation from living donors

BACKGROUND: Although living donor liver transplantation for small pediatric patients is increasingly accepted, its expansion to older/larger patients is still in question because of the lack of sufficient information on the impact of graft size mismatching. METHODS: A total of 276 cases of living donor liver transplantation, excluding ABO-incompatible, auxiliary, or secondary transplants, were reviewed from graft size matching. Forty-three cases were highly urgent cases receiving intensive care preoperatively. Cases were categorized into five groups by graft-to-recipient weight ratio (GRWR): extra-small-for-size (XS; GRWR<0.8%, 17 elective and 4 urgent cases), small (S; 0.8< or =GRWR< 1.0%, 21 and 7), medium (M; 1.0< or =GRWR<3.0%, 119 and 19), large (L; 3.0< or =GRWR<5.0%, 67 and 10), and extra-large (XL; GRWR> or =5.0%, 9 and 3). RESULTS: Smaller-for-size grafts were associated not only with larger and older recipients, but also with rather older donors. Posttransplant bilirubin clearance was delayed and aspartate aminotransferase corrected by relative graft size was higher in XS and S. Posttransplant hemorrhage and intestinal perforation were more frequent in XS and S, and vascular complications and acute rejection were more frequent in larger-for-size grafts. Consequently, graft survival in XS (cumulative 58% and actuarial 42% at 1 year) and S (76% and 74%) was significantly lower compared with that in M (93% and 92%) in elective cases. Graft survival in L (83% and 82%) and XL (75% and 71%) did not reach statistical significance. CONCLUSIONS: The use of small-for-size grafts (less than 1% of recipient body weight) leads to lower graft survival, probably through enhanced parenchymal cell injury and reduced metabolic and synthetic capacity. Although large-for-size grafts are associated with some anatomical and immunological disadvantages, the negative impact is less pronounced.     

Long-term outcome of living related liver transplantation for patients with intrapulmonary shunting and strategy for complications

BACKGROUND: In 320 living related liver transplantation performed between June 1990 and September 1997, there were 21 living related liver transplantation for patients with intrapulmonary shunting, manifested by digital clubbing, cyanosis, and dyspnea. We report the long-term outcome for more 6 months and our strategy to overcome complications in these recipients. PATIENTS: A total of 21 patients (age range 2-33 years, 19 children and 2 adults, 6 males and 15 females) were classified into three grades according to shunt ratio calculated by TcMAA pulmonary scintigraphy; 5 in mild group (shunt ratio: less than 20%), 6 in moderated group (20%-40%), and 10 in severe group (more than 40%). The original underlying liver disease was biliary atresia in all patients. RESULTS: Spearmen's correlation coefficient rank test revealed that shunt ratio correlated significantly with PaO2 in room air (P=0.0001), PaO2 in 100% oxygen (P=0.0004), hematocrit (P=0.0276), and period of dyspnea before transplantation (P=0.023). COMPLICATIONS: Wound infection occurred in 80, 66, and 80%, and bile leakage in 20, 0, 40% in mild, moderate, and severe group, respectively. Patients who had portal vein thrombosis, and intracranial complication were classified as severe group and the incidence was 20 and 20%, respectively. The patient actuarial one year survival was 80, 66.7, and 48%, in mild, moderate, and severe group, respectively, although there was no significant difference. All patients who survived improved hepatopulmonary syndrome and the length of period required for the resolution was significantly correlated to the preoperative shunt ratio (P=0.023). COMMENTS: Patients with severe shunting are susceptible to wound infection and bile leak. The trend of higher incidence of portal thrombosis and intracranial complications in the severe group was closely related high hematocrit. Secure surgical technique to reduce bile leak and delayed primary wound closure to reduce wound infection were found to be effective. Anticoagulant therapy by infusing heparin through the portal vein followed by coumadin could prevent fatal portal vein thrombosis without counter risk of fatal cerebral hemorrhage.     

Total Esophagectomy versus Proximal Esophagectomy for Esophageal Cancer at the Cervicothoracic Junction

To investigate the adequate extent of esophagectomy and lymphadenectomy for an esophageal cancer localized at the cervicothoracic junction, the mortality and morbidity rates, survival rates, and patterns of recurrence were retrospectively analyzed in two groups—14 patients who underwent total esophagectomy with or without laryngectomy and 15 patients who underwent proximal esophagectomy with or without laryngectomy—at Kurume University Hospital from 1981 to 1996. Proximal esophagectomy with or without laryngectomy resulted in a lower hospital mortality rate and better overall survival for patients who underwent curative esophagectomy compared with total esophagectomy with or without laryngectomy. Multivariate analysis indicated that the extent of esophagectomy (total esophagectomy versus proximal esophagectomy) was not a prognostic factor. The incidence of recurrence was not different between the two groups. Lymph node metastasis or recurrence from such esophageal cancers was localized to the neck and upper mediastinum. For an esophageal cancer localized at the cervicothoracic junction, therefore, proximal esophagectomy with or without laryngectomy and with cervical and upper mediastinal lymphadenectomy could be better indicated for preselected patients.     

Glucocorticoid blockade does not abrogate tumor-induced cachexia

Cancer-induced cachexia is a common manifestation observed in patients with malignancies. Elevated levels of circulating glucocorticoids and interleukin-6 (IL-6) have been observed in cancer patients with cachexia and are implicated as major mediators in this process. The purpose of this study was to investigate the role of circulating glucocorticoid levels as primary mediators in cancer-induced cachexia. We evaluated whether inhibition of glucocorticoids with the receptor antagonist RU-486 could abrogate the detrimental wasting of muscle and adipose tissues seen in a well-characterized murine tumor-induced cachexia model. Mice (12/group) were randomized to control, tumor-bearing, control + vehicle, or tumor-bearing + glucocorticoid receptor antagonist groups. Circulating serum glucocorticoid and IL-6 levels were measured in addition to multiple body composition parameters, such as total body weight, lean body mass, and adipose content. The results of this study indicate a significant physiological alteration in the tumor-bearing host that causes severe and detrimental changes in body composition parameters. Regression analysis demonstrated a significant correlation between increased circulating glucocorticoid levels and alterations in body composition parameters. These observed defects were not abrogated with the administration of a glucocorticoid receptor antagonist. We therefore conclude that the untoward effects of tumor-induced cachexia are not mediated primarily by the peripheral effects of high circulating glucocorticoid levels but may involve a complex interaction with IL-6.     

Induction of heme oxygenase-1 as a response in sensing the signals evoked by distinct nitric oxide donors.

To gain insights into the cellular responses evoked by nitric oxide (NO), we have studied the effects of NO donors with distinct chemistries on the expression of heme oxygenase-1 mRNA by northern blot analysis. The expression levels of heme oxygenase-1 mRNA were increased significantly in DLD-1 human colorectal adenocarcinoma cells by treatment with each of three NO donors: sodium nitroprusside (SNP), S-nitroso-L-glutathione (GSNO), and 3-morpholinosydnonimine (SIN-1). A combination of SIN-1 plus SNP or GSNO additively increased heme oxygenase-1 mRNA expression, whereas synergistic induction was seen with SNP plus GSNO. The SNP-mediated induction was not affected noticeably by extracellular superoxide dismutase, catalase, or mannitol, while the induction by SIN-1 was attenuated by superoxide dismutase. Thus, the SNP-mediated induction of heme oxygenase-1 mRNA expression may be independent of reactive oxygen species, and the induction by SIN-1 is mediated partly by peroxynitrite, which is generated by immediate reaction of NO and superoxide anion. Transient transfection assays suggested that treatment with SNP, but not with GSNO or SIN-1, increased the expression of a reporter gene through a cis-acting element, including the cadmium-responsive element, of the human heme oxygenase-1 gene. These results suggest that SNP induces heme oxygenase-1 mRNA expression through a mechanism different from that for GSNO or SIN-1. We therefore propose that induction of heme oxygenase-1 represents a common cellular response in sensing the signals evoked by distinct NO donors.     

Involvement of cysteinyl leukotrienes in biphasic increase of nasal airway resistance of antigen-induced rhinitis in guinea pigs

We examined the effect of a specific cysteinyl leukotriene (LT) receptor antagonist, 4-oxo-8-[4-(4-phenylbutoxy)benzoylamino]-2-(tetrazol-5-yl)-4 H-1-benzopyran hemihydrate (pranlukast), on a novel model of allergic rhinitis induced by repeated intranasal ovalbumin challenge in actively sensitized guinea pigs. Repeated intranasal ovalbumin challenge caused a biphasic increase of nasal airway resistance, peaking 0.5 and 4 h after the final challenge. The early-phase response was accompanied by an increase in sneezing and nasal secretion, while that in the late phase was associated with edema and eosinophil infiltration of the nasal mucosa. Analysis of nasal lavage fluid showed that cysteinyl LTs increased in both phases. Pranlukast, when administered 1 h before every ovalbumin challenge, dose-dependently suppressed the increase of nasal airway resistance in the early- and late phase with evidence of histopathological improvements in the late phase. Pranlukast, however, failed to suppress sneezing and nasal secretion. We suggest that cysteinyl LTs play an important role in allergic rhinitis especially in the nasal obstruction due to edema of the nasal mucosa membrane.