Mortality risk factors and fulminant sub-phenotype in anaerobic bacteremia: a 10-year retrospective, multicenter, observational cohort study.

PURPOSE: During the last decade, the incidence of anaerobic bacteremia (AB) has been increasing. Patients with AB may develop complex underlying diseases, which can occasionally be accompanied by fatal or fulminant outcomes. However, the risk factors for AB-related mortality remain unclear. Herein, we sought to elucidate the risk factors for AB-related mortality. METHODS: In this multicenter, retrospective, observational study, we enrolled patients with culture-proven AB from six tertiary hospitals in Japan, between January 2012 and December 2021. Data on patient and infection characteristics, laboratory findings, treatment, and outcome were collected, and their associations with mortality were analyzed. RESULTS: A total of 520 participants were included. The 30-day mortality in the study cohort was 14.0% (73 patients), and malignant tumors were frequently observed comorbidities in 48% of the entire cohort. Multivariable logistic regression analysis showed a Charlson comorbidity score of > 6, serum creatinine level of > 1.17 mg/dL, and hypotension to be independent risk factors for 30-day mortality in AB (odds ratios [ORs] 2.12, 2.25, and 5.12, respectively; p < 0.05), whereas drainage significantly reduced this risk (OR, 0.28; p < 0.0001). Twelve patients (2.3% of the whole cohort and 16.4% of the deceased patients) presented with extremely rapid progression leading to fatal outcome, consistent with "fulminant AB." CONCLUSIONS: This study identified acute circulatory dysfunction and performance of drainage as independent predictive factors for 30-day AB-related mortality and revealed the existence of a fulminant AB sub-phenotype. Our findings could serve as a practical guide to predict the clinical outcomes of AB.

Predictive values of immune indicators on respiratory failure in the early phase of COVID-19 due to Delta and precedent variants.

Background: Immune response indicators in the early phase of COVID-19, including interferon and neutralizing responses against SARS-CoV-2, which predict hypoxemia remains unclear. Methods: This prospective observational study recruited patients hospitalized with COVID-19 (before emergence of omicron variant). As the immune indicators, we assessed the serum levels of IFN-I/III, IL-6, CXCL10 and VEGF, using an ELISA at within 5 days after the onset of symptoms, and serum neutralizing responses using a pseudovirus assay. We also assessed SARS-CoV-2 viral load by qPCR using nasal-swab specimens and serum, to assess the association of indicators and viral distribution. Results: The study enrolled 117 patients with COVID-19, of which 28 patients developed hypoxemia. None received vaccine before admission. Serum IFN-I levels (IFN-α and IFN-ß), IL-6, CXCL10, LDH and CRP were significantly higher in patients who developed hypoxemia. A significant association with nasopharyngeal viral load was observed only for IFN-I. The serum levels of IFN-α, IL-6, CXCL10 were significantly associated with the presence of RNAemia. Multivariable analysis showed higher odds ratio of IFN-α, with cut-off value of 107 pg/ml, in regard to hypoxemia (Odds ratio [OR]=17.5; 95% confidence interval [CI], 4.7-85; p<0.001), compared to those of IL-6, >17.9 pg/ml (OR=10.5; 95% CI, 2.9-46; p<0.001). Conclusions: This study demonstrated that serum IFN-α levels in the early phase of SARS-CoV-2 infection strongly predict hypoxemic respiratory failure in a manner different from that of the other indicators including IL-6 or humoral immune response, and instead sensitively reflect innate immune response against SARS-CoV-2 invasion.

Fibronectin plays a major role in hypoxia-induced lenvatinib resistance in hepatocellular carcinoma PLC/PRF/5 cells.

Resistance to lenvatinib mesylate (LEN), a systemic chemotherapy that can be administered orally, has been a major issue for treatment of hepatocellular carcinoma (HCC). Although HCC is the tumor that most exhibits intratumoral hypoxia, which has been shown to be involved in the development of treatment resistance, there are no reports of LEN resistance in HCC treatment under hypoxia. The purpose of our study was to elucidate the mechanism of treatment resistance to LEN under hypoxia using HCC cell lines. We confirmed LEN resistance under hypoxic conditions in HCC cell lines. There was a significant increase in the IC50 value of PLC/PRF/5 cells from 13.0±0.8 µM in normoxia to 21.3±1.1 µM in hypoxia, but in HepG2 cells, the increase was not significant. To elucidate the LEN resistance mechanism of PLC/PRF/5 cells under hypoxia, we performed microarray analysis and extracted genes that are thought to be related to this mechanism. Furthermore, in-silico analysis confirmed significant changes in the extracellular matrix, and among them, FN1 encoding fibronectin was determined as the hub of the gene cluster. The expression of fibronectin in PLC/PRF/5 cells examined with immunofluorescence staining was significantly elevated in and outside of cells under hypoxia, and tended to decrease when cells were exposed to LEN under normoxia. Furthermore, the fibronectin concentration in the culture solution of PLC/PRF/5 cells examined by ELISA was 2.3 times higher under hypoxia than under normoxia under LEN(-) conditions, and 1.6 times higher under hypoxia than under normoxia under LEN(+) conditions. It is assumed that in PLC/PRF/5 cells, fibronectin is probably suppressed as an indirect effect of LEN under normoxia, but transcription factors such as HIF-1α are induced under hypoxia, thus enhancing the production of fibronectin and attenuating the effect of LEN, resulting in drug resistance. This behavior of fibronectin with LEN exposure under hypoxia is probably specific to PLC/PRF/5 cells. Further studies should verify the combined effective inhibition of fibronectin and the MAPK pathway as a promising therapeutic strategy to enhance the value of LEN in HCC treatment.

Activation of protein kinase A and C prevents recovery from persistent depolarization produced by oxygen and glucose deprivation in rat hippocampal neurons.

Intracellular recordings were made from rat hippocampal CA1 neurons in rat brain slice preparations to investigate whether cAMP-dependent protein kinase (PKA) and calcium/phospholipid-dependent protein kinase C (PKC) contribute to the membrane dysfunction induced by oxygen and glucose deprivation (OGD). Superfusion of oxygen- and glucose-deprived medium produced a rapid depolarization ∼5 min after the onset of the superfusion. When oxygen and glucose were reintroduced immediately after the rapid depolarization, the membrane depolarized further (persistent depolarization) and reached 0 mV after 5 min from the reintroduction. The pretreatment of the slice preparation with PKA inhibitors, H-89 and Rp-cAMPS, and an adenylate cyclase inhibitor, SQ 22, 536, significantly restored the membrane toward the preexposure potential level after the reintroduction of oxygen and glucose in a concentration-dependent manner. On the other hand, a phospholipase C inhibitor, U73122, a PKC inhibitor, GF109203X, and a nonselective protein kinase inhibitor, staurosporine, also significantly restored the membrane after the reintroduction. Moreover, an inositol-1,4,5-triphosphate receptor antagonist, 2-aminoethyl diphenylborinate, and calmodulin inhibitors, trifluoperazine and W-7, significantly restored the membrane after the reintroduction, while neither an α-subunit-selective antagonist for stimulatory G protein, NF449, a Ca(2+)/calmodulin-dependent kinase II inhibitor, KN-62, nor a myosin light chain kinase inhibitor, ML-7, significantly restored the membrane after the reintroduction. These results suggest that the activation of PKA and/or PKC prevents the recovery from the persistent depolarization produced by OGD. The Ca(2+)/calmodulin-stimulated adenylate cyclase may contribute to the activation of PKA.

Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis.

Tumour growth depends on angiogenesis, which is closely associated with vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Extracellular MMP inducer (EMMPRIN) was reported to involve in the progression of malignancies by regulating expression of VEGF and MMPs in stromal cells. To clarify the role of EMMPRIN in progression and angiogenesis of gastric carcinoma, expression of EMMPRIN, ki-67, MMP-2, MMP-9 and VEGF was examined on tissue microarray containing gastric carcinomas (n=234) and non-cancerous mucosa adjacent to carcinoma (n=85) by immunohistochemistry. Additionally, microvessel density (MVD) was assessed after labelling with anti-CD34 antibody. Extracellular MMP inducer expression was compared with clinicopathological parameters of tumours, including levels of ki-67, MMP-2, MMP-9 and vascular endothelial growth factor (VEGF), MVD as well as survival time of carcinoma patients. Gastric carcinoma cell lines (HGC-27, MKN28 and MKN45) were studied for EMMPRIN expression by immunohistochemistry and Western blot. Extracellular MMP inducer expression was gradually increased from normal mucosa to carcinomas through hyperplastic or metaplastic mucosa of the stomach (P<0.05). There was strong EMMPRIN expression in all gastric carcinoma cell lines despite different levels of glycosylation. Extracellular MMP inducer expression was positively correlated with tumour size, depth of invasion, lymphatic invasion, expression of ki-67, MMP-2, MMP-9 and VEGF of tumours (P<0.05), but not with lymph node metastasis, UICC staging or differentiation (P>0.05). Interestingly, there was a significantly positive relationship between EMMPRIN expression and MVD in gastric carcinomas (P<0.05). Survival analysis indicated EMMPRIN expression to be negatively linked to favourable prognosis (P<0.05), but not be independent factor for prognosis (P>0.05). Further analysis showed three independent prognostic factors, depth of invasion, lymphatic and venous invasion, to influence the relationship between EMMPRIN expression and prognosis. Upregulated expression of EMMPRIN possibly contributes to genesis, growth and local invasion of gastric carcinomas. Altered EMMPRIN expression might enhance growth, invasion and angiogenesis of gastric carcinoma via upregulating MMP expression of both stromal fibroblasts and gastric cancer cells and could be considered as an objective and effective marker to predict invasion and prognosis.

Genetic variation in ABCB1 influences paclitaxel pharmacokinetics in Japanese patients with ovarian cancer.

Paclitaxel, an antineoplastic agent used for the treatment of ovarian cancer, is metabolized by cytochrome P450 (CYP)3A4 and CYP2C8 and is excreted from cells by ATP-binding cassette (ABCB1) (multi-drug resistance [MDR1], P-glycoprotein). Expression of these proteins is regulated by pregnane X receptor (PXR). Although there are common genetic polymorphisms in the genes encoding these proteins, their effect on the clinical efficacy of paclitaxel is unclear. We therefore examined the relationship of the paclitaxel pharmacokinetics in 13 patients with ovarian cancer to polymorphisms in CYP2C8, CYP3A5, ABCB1, and PXR. We found high interindividual variability in the plasma concentrations of two metabolites, 6alpha-hydroxypaclitaxel and p-3'-hydroxypaclitaxel. All the patients were genotyped as CYP2C8*1/*1. Neither the CYP3A5 A6986G (CYP3A5*3) nor the PXR C-25385T alleles were associated with altered plasma concentrations of paclitaxel and its metabolites. ABCB1 T-129C, T1236C, and G2677(A,T), however, was associated with lower area under the plasma concentration-time curve (AUC) of paclitaxel. We also observed a significant correlation between the AUC (r=-0.721) or the total clearance of paclitaxel (CL(tot)) (r= 0.673) and the ABCB1 mutant allele dosage in each patient. Taken together, our findings suggest that interindividual variability in paclitaxel pharmacokinetics could be predicted by ABCB1 genotyping.

Giant intracranial aneurysm of the anterior communicating artery treated by direct surgery using A3-A3 side-to-side anastomosis and A3-RA graft-STA anastomosis.

We describe a giant aneurysm of the anterior communicating artery (ACoA) which was treated with a STA-RA graft-A3 bonnet bypass and A3-A3 side-to-side anastomosis. A giant and partially thrombosed ACoA aneurysm was partially coated 3 years before his current presentation, its gradual increase producing visual field disturbances. An A3-A3 side-to-side anastomosis and STA-RA graft-A3 bonnet bypass were performed. The aneurysm was dissected, and the thrombus removed under transient parent-artery occlusion. The aneurysmal neck was successfully clipped without encountering ischemic changes. This strategy may be useful for treating giant or thrombosed aneurysms in the region of the ACoA.

Neuroprotective mechanisms of lidocaine against in vitro ischemic insult of the rat hippocampal CA1 pyramidal neurons.

To compare neuroprotective effects of lidocaine and procaine against ischemic insult, intracellular recordings were made from rat hippocampal CA1 pyramidal neurons in slice preparations. Superfusion of the slices with oxygen- and glucose-deprived medium (in vitro ischemia) produced a rapid depolarization 6 min from the onset. When oxygen and glucose were reintroduced, the membrane depolarized further until it reached 0 mV, and thereafter the membrane showed no functional recovery. Pretreatment with lidocaine (10 microM), but not procaine (50 microM), restored the membrane potential after the reintroduction of oxygen and glucose. Lidocaine, compared to procaine, significantly inhibited the reduction in both tissue ATP content and flavoprotein fluorescence during and after in vitro ischemia. Under electron microscopy, only lidocaine well preserved the structure of mitochondria in the CA1 pyramidal cell body. Extracellular recordings revealed that procaine reduced the field postsynaptic potential whereas lidocaine augmented it. Both drugs reduced the presynaptic volley dose-dependently. Neither lidocaine nor procaine significantly affected a rapid rise of the intracellular Ca2+ level produced by in vitro ischemia in the CA1 region. All the results suggest that the neuroprotective lidocaine action is due to the protection of the mitochondria to maintain the tissue ATP content during and after in vitro ischemia.

A new tumour forceps for use during removal of pineal region tumours.

A new forceps for grasping and cutting tumour in a narrow surgical field is described. The working length is 12 cm and the grasping element at the tip is 1 mm in diameter. To avoid damage to surrounding structures caused by pulling out the tumour, the grasping portion consists of two hollow cylinders with sharp edges that divides, rather than tears tissue.

[A case of iatrogenic carotid artery dissection treated with radial artery graft].

A case of iatrogenic intracranial artery dissection is reported. A 52-year-old female developed severe headache and nausea. Brain CT showed diffuse subarachnoid hemorrhage. On admission, carotid angiography revealed an aneurysm in the right middle cerebral artery and the intact right internal carotid artery. The aneurysm was clipped successfully. Carotid angiography on day 7 revealed dissection in the right internal carotid artery. Repeated angiograms at 10 and 31 days showed progression of the carotid artery dissection. Findings of ECD-SPECT on day 31 (Balloon occlusion test) suggested low perfusion of the right internal carotid artery territory. The patient underwent surgical reconstruction of the right internal carotid artery using a radial artery. She presented with right abducens nerve palsy three days after the radial artery graft. The patency of the radial artery graft was proved by the post-operative angiography. Internal carotid artery dissection may occur spontaneously or as a result of trauma. An iatrogenic dissection is an uncommon complication of cerebral angiography. There are no evidence-based guidelines for the treatment although anticoagulation therapy is most commonly used. The present case emphasizes the usefulness of radial artery graft for traumatic carotid artery dissection.

[Study of remanent magnetization of the human body: lung and liver tissues].

In this study, we used lung and liver tissue specimens distracted from tissue to investigate remanant magnetization, and found that specimens with a volume of 6 mm3 had an intensity of 10(-10) Am2, which was significantly stronger than the noise level of the superconducting magnetometer. This finding indicates that both lung and liver tissues contain magnetic materials. We speculated that biological magnetite is the magnetic material in these tissues. In addition, we found that lung tissue specimens with strong magnetization had correspondingly strong magnetized findings in the liver tissue specimens. In a comparison of magnetization in lung cancer tissue specimens and normal lung tissue, no significant relationship was noted, but two of the lung cancer tissue specimens showed strong magnetization. The number of lung cancer specimens studies was insufficient to investigate the relation between the magnetization (accumulation of magnetic materials) and lung cancer, and further studies are necessary. The magnetic properties of two lung cancer tissue specimens showing strong magnetization were further investigated, and an alternating field demagnetization experiment showed that their magnetization was composed of a unit stable vector, which indicates that the lung tissue may have been magnetized after the accumulation of magnetic materials. The Wohlfarth ratio (Moskowitz et al., 1989) of them was less than 0.5, which suggests that magnetic materials are distributed in clusters in lung tissue.

Functional, metabolic, and histological changes of vascular tissues after warm ischemia.

We examined functional, metabolic, and histological changes in the aortic tissue of rats after the period of warm ischemia ranging from 0 to 24 hours to determine the window of time in which grafts can be optimally viable for harvest. Sixty aortas from Brown Norway rats obtained after warm ischemia were used and changes in contraction, endothelial-dependent or -independent vasodilatation, cell viability, and histology were examined. Maximal contraction induced by norepinephrine and potassium chloride decreased time-dependently after exposure to warm ischemia. The warm ischemic period when 50% of the maximal contractile response of freshly isolated arteries was preserved, ranged from 6 to 8 hours. Maximal endothelium-dependent relaxation induced by acetylcholine decreased along with the time of warm ischemia. Endothelium-independent relaxation induced by sodium nitroprusside and forskolin was unaltered for up to 9 hours. Cell viability gradually decreased, and a significant negative correlation was found between warm ischemic period (T: hours) and cell viability (V: %) (V=101.9-2.35T; r(2)=0.96; p<0.0001). Cell viability was greater than 70% within 12 hours postmortem. Histologically, after 9-hour-warm ischemia irreversible changes were detected. Results suggest that the period of warm ischemia for up to 6 hours would be acceptable for preservation of tissue viability.

Physician's attitudes towards disclosure of cancer diagnosis to elderly patients: a report from Tokyo, Japan.

Physicians' attitudes towards the disclosure of a cancer diagnosis to 114 consecutive patients (age range, 65-93 years; median 78 years) admitted to the Tokyo Metropolitan Tama Geriatric Hospital from April 1994 to May 1995 were analyzed utilizing a questionnaire administered to the attending physicians. Eighty-seven patients (76%) had been informed of their diagnosis before the initiation of cancer treatment, while 27 patients (24%) were not told. 'To carry out the treatment under patient's understanding' and 'consideration for patient's quality of life' were the major reasons for diagnosis disclosure, while 'lack of patient's ability to understand the information' and 'family's wish that the patient not be informed of the truth' were the major reasons for non-disclosure. Dementia, deteriorated performance status, and non-curability were major factors related to non-disclosure. Even with decisional ability, 15% of patients were not told their cancer diagnosis because wishes of their families were preferred. The current results suggest that telling cancer diagnosis to the elderly patients will not yield negative attitude of the patients and that there is no rationale for physicians to hesitate to disclose cancer diagnosis merely because of patient's high age.

Study on the role of G1 cyclins in Epstein-Barr virus-associated human lymphomas maintained in severe combined immune deficiency (SCID) mice.

Five Epstein-Barr virus (EBV)-positive human lymphoma cell lines maintained in severe combined immune deficiency (SCID) mice were used to investigate the role of G1 cyclins in EBV-induced lymphomagenesis. All the primary tumors had been negative for EBV but became positive after establishment in SCID mice, with monoclonal immunoglobulin gene rearrangement and EBV monoclonality. To compare the expression status of G1 cyclins, these EBV-associated lymphoma lines (6 EBV[-] human SCID mouse lymphoma lines, 13 human B cell lymphomas and 8 samples of human tonsil tissue) were examined by reverse transcription-polymerase chain reaction-Southern blotting, Western blotting and immunohistochemistry. mRNA expression of cyclin D1 (CCND1), cyclin D2 (CCND2), cyclin E (CCNE), cyclin-dependent kinase 2 (CDK2) and 4 (CDK4) was found in all 3 types of lymphomas. Western blotting demonstrated identical results. Immunohistochemistry revealed CCND1 to be negative in all lymphomas. CCND2 was positive and restricted to the nuclei in all EBV(+) SCID mouse lymphoma lines, whereas it was limited to the cytoplasm in half of the EBV(-) counterparts. CCNE was positive in the nuclei in all EBV(+) but negative in all EBV(-) SCID mouse lymphoma lines. Immunoprecipitation of EBV(+) and (-) SCID mouse lymphomas for CCND1, CCND2 and CCNE vs. p21, PCNA and CDK2 or CDK4 demonstrated that, in EBV(+) SCID lines, CCND2/CDK4 complexes were present without binding to p21, suggesting independence from p21 regulation. In EBV(-) SCID mouse lymphomas, half of the cases showed complex formation of CCND2/CDK4 without binding of p21. In contrast, CCND1/CDK4 and CCNE/CDK2 were under regulation of p21 in both EBV(+) and (-) lymphomas. These results suggest that differential expression of CCNDs, CCNE and CDKs, as well as variation in their subcellular localization and association with CDK-inhibitor protein, could explain differences in cell proliferation between EBV(+) and EBV(-) lymphomas.

Malignant mesothelioma in Japan: analysis of registered autopsy cases.

In the Annual of the Pathological Autopsy Cases in Japan, issued by the Japanese Society of Pathology from 1958 to 1996, a total of 1,846 (0.17%) malignant mesothelioma cases (1,287 male, 558 female, 1 unknown) were registered among 1,056,259 autopsy cases. The frequency of mesothelioma (number of cases/total autopsy cases) was 0.10% (461/440,334) for the term 1958-1979, 0.18% (716/390,124) for 1980-1989, and 0.30% (669/225,801) for 1990-1996; the frequency of cases increased significantly over the time periods (p < .0001). Among 1,785 cases for which tumor sites were ascertained, there were 1,213 pleural mesothelioma (68.0%), 431 peritoneal (24.1%), 108 pericardial (6.1%), 6 tunica vaginalis testis (0.3%), and 28 "others" (1.6%). Histological cell type was noted in 598 cases; 245 (41.0%) were epithelial, 168 (28.1%) were biphasic, and 185 (30.9%) were sarcomatous. Seventy-three (0.007%) cases of malignant mesothelioma with asbestosis were found during the entire 39-y period. The frequency of those with asbestosis (number of cases/total autopsy cases) was 0.001% (5/440,334) for the term 1958-1979, 0.006% (27/390,124) for 1980-1989, and 0.018% (41/225,801) for 1990-1996; this increase over time was statistically significant (p < .0001). Researchers expect that cases of asbestos-related mesothelioma will increase in Japan in the future. Tumor sites and histological cell types of mesothelioma with asbestosis did not differ from those in individuals without asbestosis.

Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients.

One hundred and thirty three gastric cancer cases were investigated immunohistochemically to clarify the biological role of survivin in gastric cancer cells using a commercially available anti-survivin antibody (SURV11A). Five gastric cancer cell lines were employed to assess localization of survivin by reverse-transcription-polymerase chain reaction (RT-PCR) Southern blotting, Western blotting and immunofluorescence, signals being found in both nucleus and cytoplasm. Survivin nuclear staining of gastric cancer cells was evident in 109 of 133 cases (82.0%) and associated with a favorable prognosis, being an independent prognosticator on multivariate analysis. Survivin nuclear positivity also correlated with younger age and lower incidence of vessel cancer invasion. In contrast, survivin cytoplasmic positivity was noted in 117 cases (88.0%) and did not correlate with any factor of progression or prognosis. The results indicate that survivin is present in the majority of gastric cancer cells but a nuclear localization may play an important physiological role in hindering tumor progression.

Autopsy cases of asbestosis in Japan: a statistical analysis on registered cases.

There are 525 (484 male, 38 female, 3 unknown) autopsy cases with asbestosis registered in the Annual of the Pathological Autopsy Cases in Japan, which is issued by the Japanese Society of Pathology for the years 1958-1996. The frequency of asbestosis (number of cases/total autopsy cases) was 0.017% (76/440,334) for the 1958-1979 time period, 0.058% (226/390,124) for 1980-1989, and 0.099% (223/225,801) for 1990-1996. There was a significant increase in asbestosis cases across the three time periods (p < .0001). The number of asbestosis cases increased markedly among individuals who worked with asbestos products, as well as among those employed in asbestos-processing factories. The frequency of malignant tumors associated with asbestosis was 61.0% (320/525), and the frequency also increased across the three time periods, from 43.4% (33/76) to 62.8% (142/226) and 65.0% (145/223), respectively. Among the 525 cases with asbestosis, there were 174 lung cancers (33.1%), 73 malignant mesotheliomas (13.9%), 29 stomach cancers (5.5%), 14 liver cancers (2.7%), 9 prostatic cancers (1.7%), 8 malignant lymphomas (1.5%), 6 laryngeal cancers (1.1%), 4 pancreas cancers (0.8%), 3 rectal cancers (0.6%), and 28 other cancers (5.3%). The frequencies of lung cancer, malignant mesothelioma, and laryngeal cancer were significantly higher in the cases with asbestosis than among the nonasbestosis cases. The number of malignant tumors related to asbestos exposure is expected to increase in the future.

Spontaneous regression of a germinoma in the pineal body after placement of a ventriculoperitoneal shunt.

The authors report a case in which a germinoma in the pineal body displayed spontaneous regression after placement of a ventriculoperitoneal (VP) shunt. Spontaneous regression of malignant tumors is extremely rare, occurring in only one of 60,000 to 100,000 patients. Although in rare cases spontaneous regression is known to occur in patients with testicular seminomas, only one case of spontaneous regression of a primary pineal germinoma has so far been reported. In the present case a 17-year-old man presented with headache. A tumor in the pineal body and acute hydrocephalus were revealed by head computerized tomography (CT) and magnetic resonance (MR) imaging, and VP shunt placement was performed. Computerized tomography scanning of the head was performed four times during a 2-week period following the operation, and the patient was temporarily discharged to return to school. At the time of discharge, CT scanning demonstrated no change in the size of the tumor. Two months later, the patient was readmitted to the hospital to undergo surgery. At that time, head MR imaging revealed regression of the tumor. The pathological diagnosis of the lesion was germinoma. The patient underwent three courses of chemotherapy, during which carboplatin and etoposide were administered, in addition to a 24-Gy dose of radiotherapy. No manifestations of nerve impairment were noticed, and the patient was observed on an outpatient basis. The authors think that the factors involved in tumor regression included the effects of the VP shunt, the effects of radiation absorbed during head CT scanning, and the role of the patient's own immune response. However, no conclusion has been reached concerning the actual cause.

[Outcomes and predictors of mortality in elderly patients requiring artificial ventilation].

We retrospectively examined the outcomes and the predictors of mortality in 97 patients aged 70 years and over (mean: 79.3 years) who required artificial ventilation for more than 3 hours. The median duration of artificial ventilation was 16 days (range: 1-85). Of these patients, 61% survived ventilator weaning and 37% were discharged from hospital alive. We performed univariate and logistic regression analysis to determine the predictors of dying before weaning and hospital discharge using severity of illness data. The predictors of hospital mortality were examined in 86 patients, excluding those who had malignant disease, all of whom died in hospital. Activities of daily living (ADL) were ranked as "bedridden", "in wheelchair", or "independent". In the three age groups-up to 70 years, 75 to 84 years and 85 years and over-the respective survival rates were 63% (weaned) and 67% (discharged), 69% (weaned) and 39% (discharged), and 33% (weaned) and 12% (discharged); the overall p values being 0.026 (weaned) and 0.003 (discharged). The predictors of dying before weaning according to univariate analysis were as follows: age (p = 0.026), respiratory or cardiac arrest on admission (p = 0.003), acute physiology score (APS) of 25 or more on admission (p = 0.000), systolic blood pressure below 90 mmHg on admission (p = 0.001), hemoglobin less than 11 g/dl (p = 0.044), and total protein less than 6 g/dl (p = 0.007). The predictors of hospital mortality by univariate analysis were as follows: age (p = 0.003), limited ADL (p = 0.001), respiratory or cardiac arrest on admission (p = 0.011), APS 25 or more on admission (p = 0.049), systolic blood pressure less than 90 mmHg on admission (p = 0.002), hemoglobin less than 11 g/dl (p = 0.028), and GOT or GPT more than 50 IU (p = 0.038). The relative risk of dying before weaning decreased in the order: respiratory or cardiac arrest on admission, systolic blood pressure less than 90 mmHg on admission, total protein less than 6 g/dl (Odds ratios: 6.04, 3.90, 3.51, respectively), or, respiratory or cardiac arrest on admission, APS more than 25 in admission, total protein less than 6 g/dl (Odds ratio: 6.94, 3.99, 3.76, respectively). The relative risk of hospital mortality decreased in the order: "bedridden", systolic blood pressure less than 90 mmHg on admission, "with wheel chair" (Odds ratios: 11.76, 6.44, 3.57, respectively). In the older patients, successful ventilator weaning was not indicative of hospital discharge. Ventilator weaning depended mainly on acute health status on admission, but hospital discharge depended also on the presence of limited ADL and preexisting malignant disease.

Determination of urinary 8-epi-prostaglandin F(2alpha) using liquid chromatography-tandem mass spectrometry: increased excretion in diabetics.

Liquid chromatography-tandem mass spectrometry (LC/MS-MS) was applied to the quantitative analysis of urinary 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) level. 8-Epi-PGF(2alpha) and its internal standard, [(2)H(4)]-8-epi-PGF(2alpha), were extracted from urine by using a solid phase extraction cartridge and loaded to LC/MS-MS in selected reaction monitoring (SRM) mode. The standard curve showed good linearity in the range of 40 pg to 10 ng (r = 0. 997). The accuracy of the added 8-epi-PGF(2alpha) ranged from 96.8 to 104.9% with a mean +/- SD of 99.5+/-2.5%. The average level +/- SD of urinary 8-epi-PGF(2alpha) in 13 healthy volunteers (five women and eight men, 31+/-7.4 years old) was 429.4+/-149.6 pg/mg creatinine. The level of seven patients with noninsulin dependent diabetes mellitus (two women and five men, 40+/-13.6 years old), 630.9+/-275.6 pg/mg creatinine, was statistically higher than that of healthy volunteers (P<0.05). This finding suggested that diabetics are in a highly oxidative condition. This simple and rapid LC/MS-MS method can be used to elucidate the pathophysiological feature of diabetes or for monitoring the curative effect.