Effective therapies against sepsis, which is commonly encountered in critical care units, have been long awaited. In this study, we examined the effects of pre-administered neuraminidase inhibitors, oseltamivir phosphate and zanamivir hydrate, on intestinal paralysis in a lipopolysaccharide (LPS)-induced endotoxicosis model in guinea pigs. Intestinal movement and body temperature of guinea pigs were measured successively. Intestinal movement was observed by telemetry using a force transducer installed on the taenia caecum. Simultaneously, body temperature was measured using a plate-type thermometer attached to the dorsum of the animal. On the 4th post-operative day, when intestinal movement was stabilized, lipopolysaccharide (LPS, E. coli, 0111:B4) was administered intraperitoneally. Oseltamivir and zanamivir were administrated orally and subcutaneously respectively, one hour prior to administration of LPS. In addition, to examine a neuraminidase activity in guinea pig, the level of free sialic acid in serum was measured using a periodate-resorcinol method. It was revealed that neuraminidase inhibitors, dosedependently prevented intestinal muscle relaxation and decreases in body temperature. Free sialic acid levels in guinea pig serum were decreased, indicating that oseltamivir effectively prevented neuraminidase activity. These results suggest that neuraminidase inhibitors can prevent LPS-induced intestinal paralysis and hypothermia inhibiting neuraminidase activity in guinea pigs, thus have a therapeutic potential for prevention of the worsening of endotoxicosis.

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Each year in Japan there are between 20-30 reported incidences of death from hymenoptera stings. The most prevalent cause of death is anaphylaxis, so that rapid diagnosis and treatment are necessary. We retrospectively examined clinical records of 400 cases with hymenoptera stings, who consulted our two hospitals in Northeastern Iwate Prefecture (Saiseikai Iwaizumi Hospital, and Emergency Critical Care Center, Iwate Prefectural Kuji Hospital) between January 2004 and December 2004. The 400 cases comprised 231 males and 169 females, and the average age was 51.2 years old (ranging from 0-92 years old). The incidence of stings was higher from July to September, and many victims were in their 50's to 70's. Most of the stinger attacks were in their upper extremities, and 323 patients experienced a single sting in each case. Others experienced more than two stings each. Fifteen cases had been transported by ambulance, and one case resulted in death. There were 31 cases (7.6%) with systemic reaction, and 14 cases (3.5%) with severe systemic reaction (dyspnea, hypotension, collapse, etc). None of the patients in the study had used Epipen^® (epinephrine self-injection carrying kit) before arriving at hospital. On the average, anaphylaxis appears from within a few minutes to 15 minutes. Yet for 23 cases examined, it took 79 minutes on the average before reaching the hospital, which greatly exceeds the time before anaphylaxis occurs. The conditions of the patients were worsened probably because they didn't have Epipen^®, which could have been used effectively before the onset of anaphylaxis. The Epipen^® was put on the market in Japan in August 2003, and can be used before the patient arrives at hospital. In preventing death due to anaphylaxis of hymenoptera stings, it is necessary to make Epipen^® known and available to those persons living in potentially affected regions.

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A 71-year-old male was admitted to our hospital with dyspnea and disturbance of consciousness approximately 7-hours after onset of fever, diarrhea, and vomiting. Following initial treatment the subject was admitted to the hospital where computed tomography scans failed to reveal the focus of infection. The subject failed to respond to multidisciplinary treatment of complications brought on by the infection, such as disseminated intravascular coagulation, and died 33 hours after onset of symptoms. Subsequent autopsy revealed a hypoplastic spleen, weighing only 3.6 g, extensive hemorrhaging in the bilateral adrenal cortexes, and hemorrhagic multiple organ failure. A blood culture revealed pneumococcus, while absence of scarring of the spleen suggested the condition resulted from congenital hypoplasia. Data presented here indicates that hypoplastic spleen led to fulminant pneumococcal infection causing Waterhouse-Friderichsen syndrome. This indicates that immune deficiency resulting from a hypoplastic spleen should be considered in the rapid onset of severe septicemia with no specific focus of infection. Here we suggest a rapid immunochromatographic assay used in detection of Streptococcus pneumonia antigens in urine samples as being useful in diagnosing such cases. We hope to use this assay in examining unexplained severe illnesses in the future and consider this a valuable tool in accumulating data.

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We present a severe case of type A influenza-associated acute encephalopathy. A 3-year-old boy developed high-grade fever at night, followed by generalized seizures on the next morning. The brain CT scan obtained at admission demonstrated a marked brain swelling in both cerebral hemispheres. The patient was treated with barbiturate and mild hypothermia therapy (34°C) to reduce the intracranial pressure. On day 17, brain edema was reduced, and consequently, the basal cisterns around the brain stem became visible. The cerebral sulci became partially visible because of the relatively high densities in the low-density brain on day 26, and these were more clearly visible in the CT findings obtained on day 39. The patient was able to move his extremities actively by the time of his discharge from our medical center on day 52. The follow-up evaluations performed over the next five years showed gradual improvement in both cognitive and motive functions, although the patient remained handicapped. He can now walk up and down the stairs without any assistance. On the contrary, the CT scan obtained after five years revealed cerebral atrophic changes instead of further improvement. The structure of the cortex returned to being unclear when compared with that revealed by the CT findings on day 39; this is in contrast with his functional recovery. Thus, not only intensive care during the acute-phase but also long-term aggressive treatment represented by rehabilitation is required against influenza-associated encephalopathy since CT scans do not necessarily reveal the extent of the functional recovery of the brain, at least in infant victims.

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We report a case of retroperitoneal hematoma associated with acquired hemophilia A. The patient was admitted to hospital with lower right abdominal pain. Computed tomography (CT) revealed a retroperitoneal hematoma. Laboratory tests showed a prolonged activated partial thromboplastin time (APTT) and very low factor VIII activity. Angiography revealed bleeding from the right lumbar artery, so transarterial embolization (TAE) was performed. However, his general condition failed to improve and emergency transfer to our hospital. After admission, repeat angiography showed bleeding from a branch of the right external iliac artery, so TAE was performed again. Laboratory tests revealed a high level of factor VIII inhibitor, and a diagnosis of acquired hemophilia A was made. Although TAE was effective for controlling arterial bleeding, venous bleeding continued and his APTT did not improve after infusion of factor VIII concentrate. Accordingly, prednisolone therapy was started to reduce the production of factor VIII inhibitor. Subsequently, the hematoma decreased in size, APTT improved, factor VIII activity increased, and factor VIII inhibitor decreased. The patient's general condition became stable. The combination of TAE and prednisolone can be effective for retroperitoneal bleeding associated with acquired hemophilia A.

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