A new method for the quantification of beta-glucan in plasma and its application in the diagnosis of postoperative infection

In order to correctly diagnose and treat severe postoperative infections, it may be critical to detect and differentiate between endotoxin derived from Gram-negative bacteria and/or beta-glucan derived from fungi. In addition to the chromogenic assay, the turbidimetric kinetic assay has been performed for the quantification of endotoxin in plasma using Limulus amebocyte lysate as previously reported. However, it is also known that beta-glucan triggers the coagulation of Limulus amebocyte lysate. In the present study, the differentiation of beta-glucan from endotoxin and its clinical application were studied. Endotoxin was able to be inactivated in plasma using one-tenth dilution by 10 per cent ethanol or distilled water, followed by heating at 100 degrees C for 120 min, without affecting the activity of coexisting beta-glucan. The treated sample was then subjected to the turbidimetric kinetic assay using Toxinometer ET-201. Using this method, as little as 30 pg/ml of beta-glucan in the plasma may be assayed separately, with the amount of circulating beta-glucan in the plasma of normal subjects being less than 50 pg/ml. On the other hand, in patients with a fungal infection, the amount of beta-glucan in their plasma was elevated significantly. Clinically, beta-glucanemia may often occur in severe postoperative infection even if fungi are not detected.     

Effects of the synthetic proteinase inhibitor, FOY, on hypercoagulability after surgery for esophageal carcinoma

Hypercoagulability develops after surgery for esophageal carcinoma, and it related closely to postoperative complications. This study evaluated the effects of the synthetic proteinase inhibitor, Cabexate Mesilate (FOY), on this hypercoagulability. The subjects used were 25 patients with a mean age of 63 who had undergone surgery for esophageal carcinoma. Of these, eight patients (test group) received FOY (2,000 mg/day) for three to 23 days after surgery, but 17 (control group) did not. In the test group, FOY controlled aggregation and release of the platelets and minimized their exhaustion. FOY almost completely checked the abnormal increase in thrombin activity which might trigger the hypercoagulability. Also, FOY suppressed the fibrinolytic activity slightly. These results indicate that FOY is effective in controlling hypercoagulability after surgery for esophageal carcinoma and in suppressing activity of the proteinases that cause both blood coagulation and fibrinolysis.     

A case of orbital apex syndrome caused by localized invasive aspergillosis successfully treated with voriconazole]

A 71-year-old man with left periorbital pain and diplopia was hospitalized for evaluation and treatment. He had a past history of untreated diabetes mellitus. Shortly after admission, the patient experienced rapid onset of visual loss in the left eye. MRI and CT showed a lesion expanding from the left orbital apex to the left pterygopalatine fossa. Invasive aspergillosis was diagnosed by open biopsy of intrasinus mucosa via the left maxillary sinus. The patient was treated with voriconazole, an antifungal agent, and marked improvements in left periorbital pain and eye movement were subsequently obtained, although visual acuity was not recovered. This is the first report documenting the clinical utility of voriconazole for sino-orbital invasive aspergillosis.     

Langerhans Cell Histiocytosis Presenting as a Varicelliform Eruption over the Entire Skin

A boy with skin eruptions resembling varicella and specific for Langerhans cell histiocytosis (LCH) is reported. At his initial visit when he was four months old, vesiculopustular lesions were present over the entire body; these had first appeared on the third day post partus. Histopathological, immunohistochemical, and electron microscopical examination confirmed the Langerhans cell phenotype and Birbeck granules in the responsible cells. He also had hydronephrosis, recurrent fever, and cutaneous bacterial infections. His parents refused further medical treatment and he died of diarrhea with cachexia about two years later. LCH may present diagnostic difficulties by manifesting as a skin eruption which resembles varicella.     

Acute hemorrhagic colitis induced by the neuraminidase inhibitor oseltamivir]

A 23-year-old woman had lower abdominal pain, diarrhea and bloody stool was admitted and given a diagnosis of influenza B. Her home doctor had started treatment by neuraminidase inhibitor (oseltamivir) the previous day. Colonoscopic examination revealed an area of hemorrhage and erosion in the left transverse colon. After halting oseltamivir treatment these symptoms disappeared and her colonoscopic findings improved. A drug-induced lymphocyte stimulation test was positive for oseltamivir. This case is the first reported case of acute hemorrhagic colitis induced by oseltamivir.     

Relationship between the thromboxane A2 receptor gene and susceptibility to cerebral infarction.

The risk of cerebral infarction (CI) in an individual is dependent on the interplay between genetic risk factors and environmental influences. Binding of thromboxane A2 (TXA2) to its receptor (TP) modulates thrombosis/hemostasis and plays a significant role in the pathogenesis of CI. The aim of the present study was to investigate the relationship between human TP gene single nucleotide polymorphisms (SNPs) and haplotypes and CI in a Japanese population. A genetic association study was performed in 194 CI patients and 365 non-CI subjects by specifically characterizing 6 SNPs in the human TP gene (rs2271875, rs768963, rs2238634, rs11085026, rs4523 and rs4806942). Analysis demonstrated that there were significant differences in the overall distribution of genotypes and dominant or recessive models of rs2271875 and rs768963 between the CI and the non-CI groups. Multiple logistic regression analysis revealed that the C allele of rs768963 was significantly associated with CI (p = 0.029), even after adjusting for confounding factors (odds ratio: 2.41). Further, the C-T-C haplotype of rs768963-rs2238634-rs4806942 was significantly more frequent in the CI group (23.0%) than in the non-CI group (17.7%). These results suggest that specific SNPs and haplotypes may have utility as genetic markers for the risk of CI and that TP or a neighboring gene is associated with the increased susceptibility to CI.     

Screening of H-ras Gene Point Mutations in 50 Cases of Bladder Carcinoma

Background Mutation converts the H-ras gene into an activated oncogene in about 10% of human bladder cancers. Codons 12 and 61 are the major "hot spots" for activation. A simple and accurate method to detect point mutations in these codons may be clinically useful for early diagnosis of bladder cancer.
Methods Bladder cancer samples from 50 patients, plus 10 samples of normal bladder mucosa, were analyzed for possible point mutation of the H-ras gene at either codon 12 or codon 61. The H-ras gene DNA segments that include these 2 codons were amplified by PCR methods, then the possible presence of a point mutation was evaluated at each codon by susceptibility of the respective DNA segments to digestion with the restriction enzyme and by dot blot hybridization assay. A bladder cancer patient who had an H-ras gene mutation was examined to see whether the mutation was also detectable in the cells released in the urine.
Results Definite or possible point mutations were found in 6 (1 2%) out of 50 bladder cancer patients, while no mutation was detected in normal mucosa. A point mutation could also be detected in cells isolated from the patient's urine sample.
Conclusion The prevalence of point mutations at codon 1 2 or codon 61 of the H-ras gene found in this study was similar to that previously estimated for human bladder cancer by DNA transfection assay. The method we have used for detecting point mutations of the H-ras gene provides a simple and highly accurate way to detect mutated cancer cells even in the urine. It may be clinically usable for early diagnosis of bladder cancer.     

Kupffer cell activation in the survival discrepancy between liver grafts from enterally and parenterally fed donors

Abstract This study was designed to investigate the effects of differences in the route of nutritional support of the donor on cold ischemia/reperfusion injury. Participation of Kupffer cells in these effects, based on the analysis of hepatic energy metabolism in early phases of reperfusion was also investigated. Orthotopic liver transplantation was performed between Large-White pigs weighing 20–30 kg after a 4-h cold preservation of the graft in Euro-Collins solution at 4°C. One group was fed orally with a standard laboratory diet (FED group, n = 5), a second group was fasted and given 20% glucose intravenously (12 kJ/kg per day) (PEF group, n = 5), and a third group was fed orally with a standard laboratory diet and given GdCI₃ (10 mg/kg) intravenously 24 h before operation (FEDGD group, n = 5). These treatments were given for 7 days prior to harvesting. The survival time was significantly longer in the PEF (34.8 ± 5.5 days) and FEDGD (28.0 ± 11.9 days) groups than in the FED (9.8 ± 2.0 days) group ( P < 0.05). The serum hyaluronic acid elimination rate determined from 1 to 2 h after reperfusion was significantly lower in the FED group than in the other two groups ( P < 0.001). The glycogen content of the livers 1 h after reperfusion in all three groups had been consumed rapidly, but the ATP content of the livers was significantly reduced in the FED group alone ( P < 0.01). Hepatic FFA clearance (C_FFA) was moderately increased in all three groups in the early phase after reperfusion, but it was higher in the FED group than in the other two groups, with significant differences 1 and 2 h after reperfusion ( P < 0.05). In conclusion, parenteral nutrition of the donors reduced cold ischemia/reperfusion injury which is related to Kupffer cell activation and, thus, was better than enteral nutrition for donor management.     

Comparison of the size of neuronal and non-neuronal histamine pools in the brain of different rat strains

Summary The size of the neuronal and non-neuronal histamine pools in the brain of three different strains of rats was measured by assuming that the -fluoromethylhistidine-induced maximal decrement of histamine represents the size of the neuronal pool. Although the total histamine levels in the brain showed a considerable interstrain variation, no significant interstrain difference was observed in the neuronal histamine level. These results suggest that the size of the neuronal histamine pool in the brain is relatively stable, whereas the size of the non-neuronal histamine pool is variable.     

Histamine turnover in the brain of morphine-dependent mice

Summary The turnover of brain histamine was examined in mice implanted subcutaneously with a morphine pellet (50 mg free base). The numbers of naloxone-precipitated jumpings and body shakes were maximum 2 and 3 days after implantation, respectively. The brain tele-methylhistamine level significantly increased (50% to 115%) during 12 h3 days after implantation of a morphine pellet, whereas the histamine level remained unchanged. The accumulation of tele-methylhistamine by pargyline treatment was significantly enhanced when pargyline was administered 12 h after implantation, suggesting an enhancement of histamine turnover. However, a similar degree of the tele-methylhistamine accumulation was induced by pargyline during 1–5 days after implantation, as compared with the accumulation in the control mice implanted with a placebo pellet. In mice undergoing morphine withdrawal by either the removal of morphine pellet or the treatment with naloxone 3 days after implantation, the degree of the pargyline-induced telemethylhistamine accumulation or the (S)--fluoromethylhistidine (-FMH)-induced histamine decrease was similar to that observed in the placebo pellet-control mice. The numbers of naloxone-precipitated jumpings and body shakes occurring in mice 3 days after implantation were not significantly affected by any of l-histidine, -FMH or metoprine. These results suggest that turnover of histamine in the brain is enhanced by acute morphine treatment and returns to the normal rate in the stage of chronic treatment and remains unchanged during the state of withdrawal. Send offprint requests to K. Saeki