Rapidly progressive brain atrophy in septic ICU patients: a retrospective descriptive study using semiautomatic CT volumetry.

BACKGROUND: Sepsis is often associated with multiple organ failure; however, changes in brain volume with sepsis are not well understood. We assessed brain atrophy in the acute phase of sepsis using brain computed tomography (CT) scans, and their findings' relationship to risk factors and outcomes. METHODS: Patients with sepsis admitted to an intensive care unit (ICU) and who underwent at least two head CT scans during hospitalization were included (n = 48). The first brain CT scan was routinely performed on admission, and the second and further brain CT scans were obtained whenever prolonged disturbance of consciousness or abnormal neurological findings were observed. Brain volume was estimated using an automatic segmentation method and any changes in brain volume between the two scans were recorded. Patients with a brain volume change < 0% from the first CT scan to the second CT scan were defined as the "brain atrophy group (n = 42)", and those with ≥ 0% were defined as the "no brain atrophy group (n = 6)." Use and duration of mechanical ventilation, length of ICU stay, length of hospital stay, and mortality were compared between the groups. RESULTS: Analysis of all 42 cases in the brain atrophy group showed a significant decrease in brain volume (first CT scan: 1.041 ± 0.123 L vs. second CT scan: 1.002 ± 0.121 L, t (41) = 9.436, p < 0.001). The mean percentage change in brain volume between CT scans in the brain atrophy group was -3.7% over a median of 31 days, which is equivalent to a brain volume of 38.5 cm3. The proportion of cases on mechanical ventilation (95.2% vs. 66.7%; p = 0.02) and median time on mechanical ventilation (28 [IQR 15-57] days vs. 15 [IQR 0-25] days, p = 0.04) were significantly higher in the brain atrophy group than in the no brain atrophy group. CONCLUSIONS: Many ICU patients with severe sepsis who developed prolonged mental status changes and neurological sequelae showed signs of brain atrophy. Patients with rapidly progressive brain atrophy were more likely to have required mechanical ventilation.

The Clinical Features of Recurrent Endometrial Cancer in Japan: Chemotherapy Instead of Radiotherapy as Postoperative Adjuvant Treatment.

OBJECTIVE: Chemotherapy is a standard adjuvant treatment after primary surgery for endometrial cancer in Japan. We aimed to characterize the clinical features of recurrent endometrial cancer (REC) patients in Japan. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 112 REC patients who were primarily treated at 1 of 3 university hospitals in Japan from 2005 to 2012. We analyzed overall survival since the first recurrence (R-OS) in accordance with several factors. RESULTS: Median patient age was 64 years. The median follow-up period was 48 months. The distributions of cancer stage and histological subtype lacked distinctive features, and most patients had a high risk for recurrence at the time of the primary surgery. Although approximately 78% of patients received adjuvant chemotherapy, 85/112 patients (76%) experienced recurrence within 2 years after the initial treatment ended. For patients receiving adjuvant chemotherapy, regional lymph node (LN) and distant-site recurrence were more frequent (>40%) than vaginal or intra-abdominal recurrence. Median survival and 5-year R-OS were 27 months and 26.1%, respectively. The R-OS was significantly better for patients aged 65 years or older, those with negative peritoneal cytology at the time of primary surgery, those with recurrence within regional LN (eg, pelvic LN or para-aortic LN under the renal vein) and/or vagina, and those who underwent surgery and/or radiotherapy after recurrence. A multivariate analysis indicated that positive peritoneal cytology, a disease-free interval of less than 12 months, recurrent lesions in 2 or 3 areas, and treatment excluding surgery or radiotherapy were independent predictors of poor prognosis after recurrence. CONCLUSIONS: Adjuvant chemotherapy was insufficient to reduce the incidence of distant recurrence. The prognosis of patients recurred within regional LN and/or vagina was significantly better than that of patients with recurrence in other lesions because of treatment with surgery and/or radiotherapy. The disease-free interval was a significant prognostic factor for REC patients.

[Delayed Traumatic Intracerebral Hematoma during Antiplatelet Therapy after Operations for Ruptured Left ICPC Aneurysm and Right Traumatic Epidural Hematoma: A Case Report].

Delayed traumatic intracerebral hematoma (DTICH) is a rare complication of head injury that appears suddenly after an interval of several days or months. Here, we report a case of DTICH during antiplatelet therapy for vasospasm following surgeries for a ruptured left internal carotid-posterior communicating (ICPC) aneurysm and right acute epidural hematoma (EDH). A 77-year-old man with no medical history was diagnosed with a subarachnoid hemorrhage (SAH) due to rupturing of a left ICPC aneurysm and a right linear fracture of the right parietal bone due to a head injury following the rupture. On day 2, the patient underwent successful clipping of the left ICPC aneurysm. Computed tomography (CT) performed post-clipping revealed a right acute EDH below the linear fracture of the right parietal bone, which was removed immediately. A next-day CT revealed minor contusions in both temporal poles. Fasudil, ozagrel, and cilostazol were administered from Day 3 post-clipping and EDH evacuation to prevent vasospasm. The contusions did not enlarge until Day 10. On Day 11, the patient became comatose, and a huge hematoma was identified in the right temporal lobe to frontal lobe. Although the hematoma was removed immediately, the patient died on Day 13. The hematoma was considered to be a rare case of DTICH that developed from a minor contusion of the right temporal lobe during antiplatelet therapy for vasospasm. In cases of aneurysmal SAH with head injury and contusion, we must pay attention to DTICH and select more deliberate treatment for vasospasm.

The anti-overactive bladder activity of KW-7158 is mediated by blocking equilibrative nucleoside transporter-1.

KW-7158 is a novel therapeutic candidate for treating overactive bladder (OAB) with a unique mode of action: suppression of sensory afferent nerves. However, the molecular target of this compound remains unknown. We herein report the identification of the KW-7158 target to be equilibrative nucleoside transporter-1 (ENT1). A membrane protein expression library of ca. 7000 genes was expressed in a dorsal root ganglion cell line, which we had previously generated, and subjected to screening for binding with a fluorescent derivative that retains high binding activity to the target. The screening revealed that only cells transfected with an ENT1 expression vector exhibited significant binding. We next performed [(3)H]KW-7158 binding experiments and an adenosine influx assay and found that KW-7158 binds to and inhibits ENT1. To further demonstrate the pharmacological relevance, we evaluated other known ENT1 inhibitors (nitrobenzylthioinosine, dipyridamole, draflazine) in an in vitro bladder strip contraction assay and the rat spinal cord injury OAB model. We found that all of the inhibitors exhibited anti-OAB activities, of which the potencies were comparable to that of adenosine influx inhibition in vitro. These studies demonstrated that the pharmacological target of KW-7158 is ENT1, at least in the rat OAB model. Our results will aid understanding of the precise mechanism of action of this drug and may also shed new light on the use of the adenosine pathway for the treatment of OAB.

The role of advanced practice nurses in improving healthcare outcomes for patients with chronic kidney disease: A scoping review protocol.

INTRODUCTION: The number of patients with chronic kidney disease is increasing worldwide; previous studies have suggested that advanced practice nurses, including nurse practitioners and clinical nurse specialists, with expert practice skills can provide high-quality care and solve complex healthcare problems. In general, nurse practitioners are generalist nurses who work as autonomous clinicians with whole personal care. Clinical nurse specialists, in contrast, are nurses with advanced nursing knowledge and skills for individuals or specific populations. Their roles are independent and different; however, similarities exist in their role in potentially improving healthcare outcomes. Although two previous studies described the role of nephrology nurse practitioners, they were systematic reviews, and their outcomes were limited. To clarify the overall aspect of advanced practice nurses' role, it is necessary to extract the studies illustrating advanced practice nurses' practices for patients with chronic kidney disease. OBJECTIVE: This study aims to map the literature describing the role of advanced practice nurses in improving healthcare outcomes for patients with chronic kidney disease. MATERIALS AND METHODS: This scoping review will be conducted using the Joanna Briggs Institute methodology for scoping review. Online databases will be searched across MEDLINE (PubMed), CINAHL (EBSCOhost), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Web of Science. Only studies published in English will be included, and no date limit will be set. Chronic kidney disease, renal replacement therapy, and advanced practice nurses as keywords and related search terms will be used. Two independent reviewers will screen the title and abstract/full-text; in case of discrepancy, a third reviewer will make the final decision. The results will be extracted and presented following the review question concerning the study characteristics, patients' characteristics, condition of chronic kidney disease, and role of advanced practice nurses.

Fucosyltransferase VII improves the function of selectin ligands on cord blood hematopoietic stem cells.

Selectins and their carbohydrate ligands mediate the homing of hematopoietic stem/progenitor cells (HSPCs) to the bone marrow. We have previously shown that ex vivo fucosylation of selectin ligands on HSPCs by α1,3 fucosyltransferase VI (FUT6) leads to improved human cord blood (CB)-HSPC engraftment in non-obese diabetic (NOD)/severe combined immune deficient (SCID) mice. In the present study, we determined whether surface fucosylation with α1,3 fucosyltransferase VII (FUT7), which is primarily expressed by hematopoietic cells, improves the function of selectin ligands on CB-HSPCs in comparison with FUT6. A saturating amount of either FUT6 or FUT7, which generates comparable levels of expression of fucosylated epitopes on CB CD34(+) cells, was used for these experiments. In vitro, FUT7-treated CB CD34(+) cells exhibited greater binding to P- or E-selectin than that of FUT6-treated CB CD34(+) cells under static or physiological flow conditions. In vivo, FUT7 treatment, like FUT6, improved the early engraftment of CB CD34(+) cells in the bone marrow of sublethally irradiated NOD/SCID interleukin (IL)-2Rγ(null) (NSG) mice. FUT7 also exhibited marginally-yet statistically significant-increased engraftment at 4 and 6 weeks after transplantation. In addition, FUT7-treated CB CD34(+) cells exhibited increased homing to the bone marrow of irradiated NSG mice relative to sham-treated cells. These data indicate that FUT7 is effective at improving the function of selectin ligands on CB-HSPCs in vitro and enhancing early engraftment of treated CB-HSPCs in the bone marrow of recipients.

Neurointensive Care of Traumatic Brain Injury Patients Based on Coagulation and Fibrinolytic Parameter Monitoring.

Coagulopathy, a common complication of traumatic brain injury (TBI), is characterized by a hypercoagulable state developing immediately after injury, with hyperfibrinolysis and bleeding tendency peaking 3 h after injury, followed by fibrinolysis shutdown. Reflecting this timeframe, the coagulation factor fibrinogen is first consumed and then degraded after TBI, its concentration rapidly decreasing by 3 h post-TBI. The fibrinolytic marker D-dimer reaches its maximum concentration at the same time. Hyperfibrinolysis in the acute phase of TBI is associated with poor prognosis via hematoma expansion. In the acute phase, the coagulation and fibrinolysis parameters must be monitored to determine the treatment strategy. The combination of D-dimer plasma level at admission and the level of consciousness upon arrival at the hospital can be used to predict the patients who will "talk and deteriorate." Fibrinogen and D-dimer levels should determine case selection and the amount of fresh frozen plasma required for transfusion. Surgery around 3 h after injury, when fibrinolysis and bleeding diathesis peak, should be avoided if possible. In recent years, attempts have been made to estimate the time of injury from the time course of coagulation and fibrinolysis parameter levels, which has been particularly useful in some cases of pediatric abusive head trauma patients.

Treatment of Geriatric Traumatic Brain Injury: A Nationwide Cohort Study.

BACKGROUND: Because of the aging of the Japanese population, traumatic brain injuries (TBI) have increased in elderly adults. However, the effectiveness and prognosis of intensive treatment for geriatric TBI have not yet been determined. Thus, we used nationwide data from the Japan Neurotrauma Data Bank (JNTDB) projects to analyze prognostic factors for intensive and aggressive treatments. METHODS: We analyzed 1,879 geriatric TBI cases (age ≥65 years) registered in four JNTDB projects: Project 1998 (P1998) to Project 2015 (P2015). Clinical features, use of aggressive treatment, and 6-month outcomes on the Glasgow Outcome Scale (GOS) were compared among study projects. Logistic regression was used to identify prognostic factors in aggressively treated patients. RESULTS: The percentage of geriatric TBI cases significantly increased with time-P1998: 30.1%; Project 2004 (P2004): 34.6%; Project 2009 (P2009): 43.9%; P2015: 53.6%, p<0.0001). Use of aggressive treatment also significantly increased, from 67.0% in P1998 to 69.3% in P2015 (p<0.0001). Less invasive methods, such as trepanation and normothermic targeted temperature management, were more often chosen for geriatric patients. These efforts resulted in a significant decrease in the 6-month mortality rate, from 76.2% in P1998 to 63.1% in P2015 (p=0.0003), although the percentage of severely disabled patients increased, from 8.9% in P1998 to 11.1% in P2015 (p=0.0003). Intraventricular hemorrhage was the factor most strongly associated with unfavorable 6-month outcomes (OR 3.79, 95% CI 1.78-8.06, p<0.0001). CONCLUSIONS: Less invasive treatments reduced mortality in geriatric TBI but did not improve functional outcomes. Patient age was not the strongest prognostic factor; thus, physicians should consider characteristics other than age.

Identification of nucleolin as a protein that binds to human papillomavirus type 16 DNA.

Transcription, replication, and segregation of human papillomaviruses (HPVs) are regulated by various host factors, but our understanding of host proteins that bind to the HPV genome is limited. Here we report the results of a search of cellular proteins that can associate with specific genomic regions of HPV type 16 (HPV16). We found that human nucleolin, an abundant nucleolar protein, was preferentially captured in vitro by an HPV16 genomic fragment from nucleotide positions (nt) 531-780. Electrophoretic mobility shift assays with a bacterially expressed nucleolin revealed that nucleolin bound to an HPV16 genomic region between nt 604 and 614 in a sequence-dependent manner. Chromatin immunoprecipitation analysis showed that both exogenous and endogenous nucleolin bound to a plasmid containing the HPV16 genomic region in HeLa cells. Furthermore, nucleolin associated with the HPV16 genome stably maintained in HPV16-infected W12 cells, suggesting that the nucleolin binding may be involved in the dynamics of the HPV genome in cells.

Amelioration of anemia in the ICGN mouse, a renal anemia model, with a subcutaneous bolus injection of erythropoietin adsorbed to hydroxyapatite matrix.

The recombinant human erythropoietin (rhEPO) is used for the treatment of patients with renal anemia. However, rhEPO should be administered subcutaneously or intravenously three times a week. The repetitive injections of rhEPO result in burdens to patients. To resolve this problem, we investigated the sustaining release methods using an rhEPO-hydroxyapatite (HAp) made by spray-drying technique as the drug delivery system. Two types of rhEPO-HAp formulations were prepared; zinc (Zn) formulation and Zn and poly-L-lactic acid (PLA) formulation. These formulations were examined in genetically anemic model, ICGN (ICR-derived glomerulonephritis) mice. According to in vivo release test of rhEPO from HAp in ICGN mice, elevated plasma concentration of rhEPO could be maintained for more than 7 days. These mice showed the amelioration of anemia for more than 3 weeks post-administration without causing any side effect. In conclusion, Zn or Zn/PLA formulation of HAp was considered to be one of the useful carriers of rhEPO for long-term improvement of anemia.

Sustained efficacy of erythropoietin with a hydroxyapatite carrier administered in mice.

For chronic kidney disease patients with renal anemia, recombinant human erythropoietin (rHuEPO) is a very effective drug; however, the treatment regime is troublesome, requiring multiple administrations each week. In the present study, we examined the efficiency of hydroxyapatite (HAp) as a drug delivery carrier for the sustained release of erythropoietin (EPO) to reduce the frequency of administration. Spray-dried HAp microparticles, formed from zinc-containing HAp (Zn-HAp) and Zn-HAp calcined at 400 degrees C, were used as carriers of EPO, and five Zn-HAp formulation samples incorporating EPO were prepared; no formulation, poly-L-lactic acid (PLA) formulation, zinc (Zn) formulation, Zn/PLA formulation, and calcined/Zn/PLA formulation. ICR mice were administered these samples or commercial rHuEPO (Epogin) as a control from dorsal neck subcutaneous, and hematological and histopathological analyses, including enzyme-linked immunosorbent assay for plasma EPO concentration, were performed. An increase in the blood EPO level was detected on days 3 and 8 post-administration. Peak hematopoiesis was delayed and higher hematological values were obtained on day 14 post-administration with no serious adverse reactions compared with the control. The Zn/PLA formulation sample was found to be most effective in reducing the initial peak while sustaining the delayed release of EPO. In conclusion, the Zn-HAp formulation samples were considered to be useful carriers for the sustained release of EPO, and the Zn/PLA formulation appears to be the most effective of five Zn-HAp formulation samples in sustaining EPO release.

The discovery and characterization of K-563, a novel inhibitor of the Keap1/Nrf2 pathway produced by Streptomyces sp.

Keap1/Nrf2 pathway regulates the antioxidant stress response, detoxification response, and energy metabolism. Previous reports found that aberrant Keap1/Nrf2 pathway activation due to Kelch-like ECH-associated protein 1 (Keap1) mutations or Nuclear factor E2-related factor 2 (Nrf2) mutations induced resistance of cancer cells to chemotherapy and accelerated cell growth via the supply of nutrients. Therefore, Keap1/Nrf2 pathway activation is associated with a poor prognosis in many cancers. These previous findings suggested that inhibition of Keap1/Nrf2 pathway could be a target for anti-cancer therapies. To discover a small-molecule Keap1/Nrf2 pathway inhibitor, we conducted high-throughput screening in Keap1 mutant human lung cancer A549 cells using a transcriptional reporter assay. Through this screening, we identified the novel Keap1/Nrf2 pathway inhibitor K-563, which was isolated from actinomycete Streptomyces sp. K-563 suppressed the expression of Keap1/Nrf2 pathway downstream target genes or the downstream target protein, which induced suppression of GSH production, and activated reactive oxygen species production in A549 cells. K-563 also inhibited the expression of downstream target genes in other Keap1- or Nrf2-mutated cancer cells. Furthermore, K-563 exerted anti-proliferative activities in these mutated cancer cells. These in vitro analyses showed that K-563 was able to inhibit cell growth in Keap1- or Nrf2-mutated cancer cells by Keap1/Nrf2 pathway inhibition. K-563 also exerted synergistic combinational effects with lung cancer chemotherapeutic agents. An in vivo study in mice xenotransplanted with A549 cells to further explore the therapeutic potential of K-563 revealed that it also inhibited Keap1/Nrf2 pathway in lung cancer tumors. K-563, a novel Keap1/Nrf2 pathway inhibitor, may be a lead compound for development as an anti-cancer agent.

Increased expression of inducible nitric oxide synthase (iNOS) in N-nitrosobis(2-oxopropyl)amine-induced hamster pancreatic carcinogenesis and prevention of cancer development by ONO-1714, an iNOS inhibitor.

Elevated protein expression of inducible nitric oxide synthase (iNOS) has been observed in human pancreatic cancers and therefore, iNOS may play important roles in pancreatic carcinogenesis. This was examined in the present study, using an experimental model with N-nitrosobis(2-oxopropyl)amine (BOP)-treated hamsters. Reverse transcription-polymerase chain reaction analysis demonstrated iNOS expression in a hamster pancreatic cancer cell line as well as in human pancreatic cancer cell lines. Immunohistochemical analysis revealed increased expression of iNOS protein in atypical hyperplasia and ductal adenocarcinomas of the pancreas in BOP-treated hamsters. In addition, iNOS expression was also observed in macrophages and islet cells in pancreatic tissue surrounding tumors. In order to assess the role of iNOS expression in carcinogenesis in the pancreas, the effects of ONO-1714 [(1S, 5S, 6R, 7R)-7-chloro-3-imino-5-methyl-2-azabicyclo[4.1.0]heptane], an iNOS inhibitor, on hamster pancreatic ductal carcinogenesis were investigated. Female Syrian golden hamsters were treated with BOP at 10 mg/kg body wt, four times for 1 week, and 1 week after the last carcinogen treatment, ONO-1714 was administered at doses of 100 and 200 p.p.m. in the diet for 15 weeks. The incidences and multiplicities of atypical hyperplasia and invasive adenocarcinoma and total adenocarcinomas (non-invasive and invasive adenocarcinomas) in the pancreas were significantly lowered by treatment with 200 p.p.m. ONO-1714. Treatment with 100 p.p.m. ONO-1714 also significantly decreased the multiplicities of invasive and total adenocarcinomas. Moreover, treatment with 200 p.p.m. ONO-1714 reduced the number of BOP-induced cholangiocellular tumors. These results suggest that iNOS plays roles in promoting pancreatic carcinogenesis in both early and late stages in hamsters.

Transcription factor human Skn-1a enhances replication of human papillomavirus DNA through the direct binding to two sites near the viral replication origin.

Human papillomavirus type 16 (HPV16) DNA replication, which requires two viral proteins E1 and E2, occurs only in the differentiating epithelium. Besides the general factors necessary for cellular DNA synthesis, other unidentified cellular factors are assumed to be involved in the regulation of HPV DNA replication. In the present study, we found that the POU-domain transcription factor human Skn-1a, which induces the terminal differentiation of keratinocytes and activates the HPV16 late promoter, enhanced the transient replication of a plasmid containing the HPV16 replication origin in HEK293 cells when co-transfected with a plasmid expressing E1 and E2. An electrophoretic mobility shift assay with a bacterially expressed human Skn-1a or an extract of HeLa cells over-expressing human Skn-1a revealed the presence of two human Skn-1a binding sites that are distinct from the known three sites, near the replication origin. A chromatin immunoprecipitation analysis showed that human Skn-1a bound to these sites in cells. Nucleotide substitutions in the sites abolished the binding of human Skn-1a and the human Skn-1a-mediated replication enhancement. The data strongly suggest that, through the binding to the two sites, human Skn-1a enhances HPV DNA replication.

Expression of surface CD1d in the extravillous trophoblast cells of early gestational placenta is downregulated in a manner dependent on trophoblast differentiation.

CD1d is a specific ligand for the invariant Valpha24Vbeta11-natural killer T (iNKT) cells that play an important role in placental development during early human pregnancy. The localization and regulation of placental CD1d expression remain unclear. Immunohistochemistry of human early gestational placentas revealed CD1d was present in villous and extravillous trophoblast (EVT) but not in syncytiotrophoblast or decidual cells. CD1d immunoreactivity in EVT cells decreased with EVT differentiation. Flow cytometry of primary cultured human trophoblast cells confirmed cell-surface expression of CD1d decreased with time in culture. These changes in CD1d expression occur at the level of transcription. TGF-beta1 secreted from the cultured EVT cells accumulated with time in culture and directly suppressed CD1d expression, as evidenced by monoclonal antibody neutralization of TGF-beta1 effects. Thus, trophoblast differentiation is characterized by TGF-beta1-mediated decreases in trophoblast cell CD1d expression. This effect may support appropriate activation of decidual iNKT cells at the maternal-fetal interface.

Validation of fast-RAMLA in clinical PET.

OBJECTIVE: Images using the fast row action maximum likelihood algorithm (fast-RAMLA), which employs half-interpolated sinograms of conventional 3DRAMLA, are immediately generated following positron emission tomography (PET) scanning and are invariably produced in the process of line-of-response RAMLA (LOR-RAMLA) reconstruction. We quantitatively and visually compared the clinical validity of dual time point [(18)F]-FDG imaging with fast-RAMLA and LOR-RAMLA. METHODS: An International Electrotechnical Commission (IEC) phantom was established in which the ratio of the activities in the hot sphere was set up and a background of 3.8:1 was scanned and reconstructed using both algorithms. The contrast recovery coefficient was then calculated. The clinical study retrospectively analyzed 35 patients (25 men and 10 women; age range 30-84 years; mean age 63.9 years) with confirmed specific pathological lesions or clinical follow-up; 21 of the patients had 51 malignant lesions and 15 had 23 benign lesions. The maximum standard uptake value (SUV(max)) was measured in all lesions using LOR-RAMLA. The maximal counts of all lesions determined manually were divided by the average count of bilateral ventricles and the aortic arch for standardization on fast-RAMLA, and the values were compared with the SUV(max) of LORRAMLA. Inter-observer variation in detection was determined among three radiologists who blindly reviewed and scored 70 maximum intensity projection images from 35 patients reconstructed using LORRAMLA and fast-RAMLA. RESULTS: We identified a quantitative correlation and determined the visual quality of lesion detection between fast-RAMLA and LOR-RAMLA and indicated usefulness and improvement point on fast-RAMLA. CONCLUSIONS: Fast-RAMLA can improve the strategy for using dual time point [(18)F] fluorodeoxyglucose positron emission tomography ([(18)F]-FDG-PET) and increase the efficiency of the [(18)F]-FDG-PET scanner.

The use of conization to identify and treat severe lesions among prediagnosed CIN1 and 2 patients in Japan.

OBJECTIVE: To evaluate the clinical efficiency of identifying patients with suspicious severe lesions by conization among prediagnosed cervical intraepithelial neoplasia (CIN) 1 and 2 patients in Japan. METHODS: The data in a Japanese nation-wide registry for cervical cancer (2009 and 2011) was collected to analyze the clinical efficacy of pre- and postdiagnosis for 13,215 Japanese women who underwent treatment by conization. Their preoperative and postoperative histologic findings and clinical outcomes were evaluated using standard statistical procedures including clinical and demographic characteristics. RESULTS: Almost half of 1,536 women who were treated by conization after the prediagnosis of CIN1 and 2 because the lesions showed no evidence of natural regression actually contained CIN1-2 (45.0%), CIN3 (47%), or invasive cancer (2.7%) in their cervical tissue. They underwent conization either for therapeutic (treatment) (78.5%) or diagnostic (21.5%) reasons. Invasive disease was diagnosed postoperatively more often in diagnostic cases (6.1%) than in therapeutic cases (2.8%). All the patients survived their diagnostic and therapeutic conization after approximately 30 months of follow up. CONCLUSION: Our study shows that the continuous observation of the prediagnosed CIN1 and 2 cases by the combination of cytology, colposcopy and histology in Japan has worked successfully to identify severe lesions by using conization as well in the process.

Enhanced thyroid carcinogenicity of N-nitrosobis(2-oxopropyl)amine in Otsuka Long-Evans Tokushima Fatty rats, a model of type II diabetes mellitus.

Epidemiologic data suggest that diabetes mellitus type II is a risk factor for several types of cancer, including pancreatic, liver, colon and thyroid cancers. In the present study, effects of diabetes/hyperlipidemia on N-nitrosobis(2-oxopropyl)amine (BOP)-induced cancer development were examined in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, model animals for non-insulin-dependent diabetes mellitus and Long-Evans Tokushima Otsuka (LETO) rats, appropriate controls. Males of both strains were given four subcutaneous injections of BOP (10 mg/kg body wt) or saline on alternative days, starting at 5 weeks of age. BOP induced tumors in a variety of tissues, including the thyroid gland, colon, kidney, liver and lung. The highest yields were noted for thyroid tumors, the incidence (P = 0.0182) and multiplicity (P < 0.001) of BOP-induced thyroid cancers with marked fibrosis being significantly higher in OLETF than in LETO rats. Interestingly, anaplastic thyroid carcinomas were observed limited to the BOP-treated OLETF rats. Additionally, a greater incidence and frequency of aberrant crypt foci, putative precursor lesions for colon tumors, was observed in the BOP-treated OLETF group. However, BOP was ineffective at inducing pancreatic ductal tumors. No thyroid, liver, lung or colon tumors were found in the OLETF and LETO rats receiving the vehicle. Significant increases in serum levels of insulin, glucose, phospholipids, triglycerides and total cholesterol were detected in the OLETF rats compared with the LETO rats, regardless of the treatment. Our results indicate that diabetic/hyperlipidemic state can enhance BOP-induced carcinogenesis of the thyroid gland and to a lesser extent the colon in OLETF rats.

Significance of magnetic resonance imaging in the diagnosis of vertebral artery injury associated with blunt cervical spine trauma.

Vertebral artery injury associated with non-penetrating cervical trauma is rare. We report 11 cases of vertebral artery injury diagnosed with magnetic resonance imaging (MRI) after blunt trauma to the cervical spine and discuss about the importance of MRI in the diagnosis of this injury. Seven cases were caused by motor vehicle accidents, three by diving accidents, and one by static compression of the neck. All of the patients had documented cervical spine fractures and dislocations. In three patients, the diagnosis of complete occlusion of the vertebral artery was made on the basis of MRI and digital subtraction angiography (DSA). In the other patients, mural injuries of the vertebral artery were demonstrated with DSA. These 11 patients presented with acute, nonspecific changes in neurological status. Two had infarctions of the cerebellum and brainstem. None were treated with anticoagulants. All of them survived and were discharged to other hospitals for physical and occupational therapy. Although DSA remains the gold standard for diagnosing vertebral artery injuries, MRI is a newer modality for assessing cervical cord injury, and it may be useful for evaluating the presence of vertebral injury after blunt cervical spine trauma.

Cerebral endothelial injury in elderly patients with severe head injury measured by serum thrombomodulin and von Willebrand factor.

Elevated serum levels of thrombomodulin (TM) and von Willebrand factor (vWf) are good indicators of injury and activation of cerebral endothelium in patients with severe simple head injury. The present study evaluated cerebral endothelial injury or activation as the serum levels of TM and vWf in elderly and younger patients with similar brain trauma, to evaluate the primary parenchymal injury of the brain. Patients with head injury were classified into the young group (16-30 years), the middle-aged group (31-65 years), and the elderly group (over 66 years). There was no difference in Glasgow Coma Scale on admission between the three groups. The serum levels of TM and vWf at 2 hours after injury were significantly higher in the elderly group than in the other groups. However, the serum levels of TM and vWf were not significantly different at 3 and 7 days after injury. Cerebral endothelial activation and injury were significantly higher in elderly patients just after head injury than in younger patients, which suggests that greater sensitivity to endothelial injury and activation may be important in the worse outcome after head injury in elderly patients compared with younger patients.