Modeling Patient Flows Using a Queuing Network with Blocking

The downsizing and closing of state mental health institutions in Philadelphia in the 1990s led to the development of a continuum care network of residential-based services. Although the diversity of care settings increased, congestion in facilities caused many patients to unnecessarily spend extra days in intensive facilities. This study applies a queuing network system with blocking to analyze such congestion processes. Blocking denotes situations where patients are turned away from accommodations to which they are referred, and are thus forced to remain in their present facilities until space becomes available. Both mathematical and simulation results are presented and compared. Although queuing models have been used in numerous healthcare studies, the inclusion of blocking is still rare. We found that, in Philadelphia, the shortage of a particular type of facilities may have created upstream blocking. Thus removal of such facility-specific bottlenecks may be the most efficient way to reduce congestion in the system as a whole.     

Utility of cycle ergometer stress testing as a measure to assess health status and physical functioning for elderly people

PURPOSE: This study was carried out to determine the prevalence of abnormal cardiovascular findings for elderly persons on exercise stress testing, and examine the relationship between exercise capacity estimated by the test and other physical functions or self-rated functional capacity cross-sectionally. METHODS: Participants of this study were 83 elderly persons (24 males and 59 females, mean age, 80 years old) who were planning to undergo a falls prevention program. A questionnaire asking about functional capacity, physical functional testing (maximum stride length, maximum speed walking for 10 meters, one leg standing time, and grip strength), and cycle ergometer exercise stress testing were applied. The initial work load of exercise testing was 15 watts, and this was progressively increased by 15 watts every 3 minutes. Exercise capacity was estimated with reference to working time and subjects were divided into tertiles for each gender. Comparisons of physical functional testing and self-rated functional capacity among the groups were then performed. RESULTS: Of 83 participants, 65 subjects (78.3%) could complete the exercise stress testing. Next to leg fatigue (46%), blood pressure elevation (26.2%) was the most common reason for termination of the test. No evidence of ischemia was found in any subject during exercise stress testing. The values for walking speed and walking pitch were highest among male participants in the third (uppermost) tertile group with statistical significance. In addition, the value for one foot standing time was highest among female participants in the third tertile group, again with statistical significance. Regarding self-rated functional capacity, the rates for subjects who reported being able to rise from a seat in a vehicle, jump over a puddle, and step on an escalator were highest among female participants in the third tertile group, with statistical significance, whereas no significant differences were seen among male participants. No one suffered falls in the previous one year in either gender in the third tertile group. CONCLUSION: As the major finding, higher exercise capacity mainly for lower-extremity work, was associated with better physical functions and self-rated functional capacity.     

The radical scavenger edaravone prevents oxidative neurotoxicity induced by peroxynitrite and activated microglia

The free radical scavenger edaravone has been used as an anti-oxidative agent in acute ischemic brain disorders. We examined the effect of edaravone on the production of nitric oxide (NO), reactive oxygen species (ROS) and proinflammatory cytokines by activated microglia, and we also examined its neuroprotective role in cortical neuronal cultures oxidatively stressed by the peroxynitrite donor N-morpholinosydnonimine (SIN-1) or activated microglia. Edaravone significantly suppressed the production of NO and ROS by activated microglia, though it did not suppress production of inflammatory cytokines. In addition, edaravone significantly suppressed neuronal cell death and dendrotoxicity induced by either SIN-1 or activated microglia in a dose-dependent manner. These results suggest that edaravone may function as a neuroprotective agent counteracting oxidative neurotoxicity arising from activated microglia, as occurs in either inflammatory or neurodegenerative disorders of the central nervous system.     

Relationships between serum magnesium levels and clinical background factors in patients with mood disorders

We measured serum magnesium (Mg) levels in 71 in-patients and out-patients with mood disorders and in 30 healthy controls and investigated the relationships between serum Mg levels and clinical background factors. Serum Mg levels were found to be significantly higher in patients with mood disorders than in controls. Serum Mg levels showed no significant correlation with patient sex, age, diagnosed subtype and disease phase in the mood disorder group. Serum Mg levels in patients with major depressive disorder who were taking psychotropic drugs were not significantly different from levels seen in patients with major depressive disorder who were not taking psychotropic drugs. These results suggest that the high serum Mg levels noted in patients with mood disorder are related to the underlying disorder itself and are not influenced by clinical background factors.     

Sequential analysis of morphological and biological properties of beta-catenin-accumulated crypts, provable premalignant lesions independent of aberrant crypt foci in rat colon carcinogenesis

Our previous study (Cancer Res., 60: 3323-3327, 2000) showed that frequent beta-catenin gene mutations are present in beta-catenin-accumulated crypts, which occur early in rodent colonic carcinogenesis, with a lack of the appearance of aberrant crypt foci (ACF). To clarify the nature of such lesions, we performed a sequential analysis of the morphological and biological properties of beta-catenin-accumulated crypts. Azoxymethane was administered s.c. to male F344 rats (15 mg/kg body weight) once a week for 3 weeks, and the animals were sacrificed at 5, 10, and 20 weeks after the carcinogen treatment. Both the number of crypts/lesion and the diameter of beta-catenin-accumulated crypts were significantly increased with time courses of 5, 10, and 20 weeks from carcinogen exposure (P < 0.01). Likewise, the histological abnormality in those crypts, assessed by semiquantitative analyses, was also increased with time (P < 0.01). Conversely, ACF did not show any increase in histological abnormality during the time course and maintained a monotonous histology throughout the experiment. The histological abnormality score for beta-catenin-accumulated crypts was significantly higher than for ACF at every time point (P < 0.001). The number of AgNOR/nucleus in beta-catenin-accumulated crypts was significantly higher than in ACF (P < 0.001). Beta-catenin-accumulated crypts were accompanied frequently by Paneth cells and had decreased hexosaminidase activity. Such data, together with the results in our previous report, strongly suggest that beta-catenin-accumulated crypts, which are independent of ACF, are truly premalignant lesions for colon cancer.     

Downregulation of vascular soluble guanylate cyclase induced by high salt intake in spontaneously hypertensive rats

1. Cyclic guanosine monophosphate (cyclic GMP)-mediated mechanism plays an important role in vasodilatation and blood pressure regulation. We investigated the effects of high salt intake on the nitric oxide (NO) - cyclic GMP signal transduction pathway regulating relaxation in aortas of spontaneously hypertensive rats (SHR). 2. Four-week-old SHR and normotensive Wistar-Kyoto rats (WKY) received a normal salt diet (0.3% NaCl) or a high salt diet (8% NaCl) for 4 weeks. 3. In aortic rings from SHR, endothelium-dependent relaxations in response to acetylcholine (ACh), adenosine diphosphate (ADP) and calcium ionophore A23187 were significantly impaired by the high salt intake. The endothelium-independent relaxations in response to sodium nitroprusside (SNP) and nitroglycerin were also impaired, but that to 8-bromo-cyclic GMP remained unchanged. On the other hand, high salt diet had no significant effects on the relaxations of aortic rings from WKY. 4. In aortas from SHR, the release of NO stimulated by ACh was significantly enhanced, whereas the production of cyclic GMP induced by either ACh or SNP was decreased by the high salt intake. 5. Western blot analysis showed that the protein level of endothelial NO synthase (eNOS) was slightly increased, whereas that of soluble guanylate cyclase (sGC) was dramatically reduced by the high salt intake. 6. These results indicate that in SHR, excessive dietary salt can result in downregulation of sGC followed by decreased cyclic GMP production, which leads to impairment of vascular relaxation in responses to NO. It is notable that chronic high salt intake impairs the sGC/cyclic GMP pathway but not the eNOS/NO pathway.     

Comparative sensitivity of three mosquito cell lines for isolation of dengue viruses

Comparative studies were carried out on three mosquito cell lines (C6/36 clone of Aedes albopictus, AP-61 from A. pseudoscutellaris, and TRA-284 from Toxorhynchites amboinensis) to determine their sensitivity to dengue virus isolation, growth, and handling characteristics for immunofluorescent testing. Virus isolation rates from human sera were the highest in the TRA-284-SF (a line adapted to serum-free medium), followed by the TRA-284 parental line and AP-61. Virus isolation was the lowest in the C6/36 line. All 3 cell lines were comparable in terms of ease of handling, but C6/36 cells were preferable for detecting infected cells by the direct fluorescent antibody test (DFAT) because of frequent cell clumping in the AP-61 and TRA-284 lines. Early detection of viral antigen of all 4 serotypes in the infected cells by DFAT was dependent upon the virus titre in the serum. The AP-61 and TRA-284-SF cells were the best for early detection and identification of viral antigen. Similarly, both AP-61 and TRA-284 cells were more resistant than C6/36 cells to toxic effects of human sera. Based on the economy of using the serum-free medium, their higher sensitivity for dengue virus isolation, and their ease of handling, it is recommended that the TRA-284-SF cell line be used for routine dengue virus isolation in laboratories with cell culture capability.