A fatal case of hemophagocytic lymphohistiocytosis associated with gestational psittacosis without symptoms of pneumonia.

Psittacosis is a zoonotic infection caused by Chlamydia psittaci. Most patients present with acute respiratory symptoms and systemic illness. When C. psittaci infects pregnant women, it causes severe clinical manifestations called gestational psittacosis. Here we report a case of gestational psittacosis. Our patient lacked respiratory symptoms, and pathological postmortem examinations revealed severe placentitis. Both DNA and immunohistochemical analyses were positive for C. psittaci from formalin-fixed paraffin-embedded tissues. The chlamydial DNA in the placenta was about 100 times more abundant than that in the lungs; therefore, the placenta rather than the lungs was the probable target of the C. psittaci infection during this pregnancy. We could not identify the source of infection. Gestational psittacosis should be considered in the differential diagnosis for fever of unknown origin during pregnancy, even in cases lacking respiratory symptoms.

[Progress on OECD Chemicals Programme (13)--SIAM 22 in Paris, 2006].

The 22nd Screening Information Data Set (SIDS) Initial Assessment Meeting (SIAM 22) was held at the Organisation for Economic Co-operation and Development (OECD) headquarters in Paris, France. The initial assessment documents of five substances (CAS numbers: 75-59-2, 80-51-3, 101-83-7, 103-24-2, 27813-02-1) sponsored by Japan were all agreed at the meeting. In this report, the documents of these substances are introduced.

[Progress on OECD chemicals programme (11)--SIAM 19 in Berlin, 2004].

The 19th Screening Information Data Set (SIDS) Initial Assessment Meeting (SIAM 19) was held in Berlin, Germany, hosted by the Germen Federal Agency for the Environment. The initial assessment documents of four substances (CAS numbers: 92-70-6, 126-33-0,131-17-9, 7580-85-0) and one category (High Molecular Weight Phthalate Esters) at SIAM 19 were submitted by the Japanese Government with or without the International Council of Chemical Associations (ICCA) and all of them were agreed at the meeting. In this report, the documents of these substances are introduced.

Efficacy of intraperitoneal continuous hyperthermic chemotherapy as consolidation therapy in patients with advanced epithelial ovarian cancer: a long-term follow-up.

This trial was performed to determine the efficacy and progression-free and overall survivals of patients with advanced ovarian cancer who had been treated with intraperitoneal hyperthermic chemotherapy (IPHC). Ten patients with advanced ovarian cancer participated in this trial and were treated with IPHC. The median progression-free and overall survival rates for all patients treated in this study were 41.2 and 70.2 months, respectively. Two of ten patients received optimal primary cytoreduction surgery followed by IPHC; four of ten, optimal interval debulking surgery followed by IPHC; and four of ten, negative second-look operation followed by IPHC. The groups had 5 and 14.5, 17.75 and 38, and 82.75 and 130.25 months median progression-free and overall survival rates, respectively. Grades 3-4 toxicity included myelosuppresion, and nephropathy was detected. One patient required blood transfusions due to grade 4 anemia and thrombocytopenia. Another patient developed grade 3 nephrotoxicity but did not require continuous hemodialysis. IPHC was feasible, produced manageable toxicity, and showed promise for the treatment of advanced ovarian cancer. Negative second-look laparotomy followed by IPHC was especially effective when consolidation intraperitoneal chemotherapy had been indicated. It produced excellent median progression-free and overall survival rates.

Metabolic monitoring of advanced uterine cervical cancer neoadjuvant chemotherapy by using [F-18]-Fluorodeoxyglucose positron emission tomography: preliminary results in three patients.

OBJECTIVE: The aim of this report is to describe the potential clinical utility of tracer [F-18]-Fluorodeoxyglucose (FDG) uptake, quantitated as a standardized uptake value (SUV) by positron emission tomography (PET), to evaluate treatment response to neoadjuvant chemotherapy (NAC) in advanced uterine cervical cancer. METHODS: We briefly describe the clinical courses of three women with advanced cervical cancer who were treated with neoadjuvant chemotherapy (NAC) prior to radical hysterectomy and who were analyzed for correlation with the decrease in tumor volume by magnetic resonance imaging (MRI), in SUV by FDG-PET, and by histologic response. RESULTS: In these individuals, tumor volume and SUV were decreased by NAC. The decrease in SUV by FDG-PET was better correlated to histologic response for NAC than MRI was in advanced cervical cancer. CONCLUSIONS: Measurement of SUV by FDG-PET has clinical utility in evaluating treatment response for NAC in advanced cervical cancer. Although work in this field is still in the early stages, this report demonstrates that SUV by FDG-PET has the potential to become the new standard for monitoring the treatment response of NAC in cervical cancer. This monitoring approach must be proven in a larger number of patients for both primary and secondary lesions and should be further explored in another gynecologic cancer.

Evaluation of positron emission tomography with tracer 18-fluorodeoxyglucose in addition to magnetic resonance imaging in the diagnosis of ovarian cancer in selected women after ultrasonography.

OBJECTIVE: To determine whether positron emission tomography (PET) with tracer 18-fluorodeoxyglucose (FDG-PET) yields additional information in the diagnosis of malignancy compared with magnetic resonance imaging (MRI) findings in selected women after screening for ovarian masses by ultrasonography (US). METHODS: After 49 patients were screened by US and physical examination (including a pelvic examination) by 2 experienced gynecologic oncologists, 38 patients suspected of having ovarian cancer were enrolled in the study. All 38 underwent MRI and FDG-PET. The results of the histologic findings were used to assess the accuracy of the imaging findings. RESULTS: Of the 38 women, 23 had malignant lesions and 15 had benign lesions. Magnetic resonance imaging, PET, and MRI with FDG-PET diagnoses had sensitivities of 91%, 78%, and 91%, respectively; specificities of 87%, 87%, and 87%, respectively; and diagnostic accuracy of 92%, 82%, and 92%, respectively. CONCLUSION: The addition of FDG-PET to MRI does not yield significant additional information for differentiation of benign from malignant ovarian masses in selected women after US.

Expression of GLUT-1 glucose transfer, cellular proliferation activity and grade of tumor correlate with [F-18]-fluorodeoxyglucose uptake by positron emission tomography in epithelial tumors of the ovary.

We evaluated whether tracer FDG uptake, quantified as an SUV by PET in ovarian epithelial tumors, correlates with clinical stage, tumor grade, cell proliferation and glucose metabolism, all of which are biomarkers for response to chemotherapy, prognosis and overall survival in ovarian cancer patients. Seventeen patients suspected of having ovarian cancer by physical examination, tumor marker analysis and anatomic imaging (such as sonography, CT and/or MRI) underwent whole-body FDG-PET within the 2 weeks prior to surgery. Seventeen epithelial ovarian tumor specimens (13 malignant tumors, 5 at stage I, 2 at stage II, 6 at stage III; 2 borderline tumors; and 2 benign lesions) were available for pathologic evaluation. They were graded histopathologically, and immunohistochemistry for MIB-1 (proliferation index marker) and GLUT-1 was performed. Correlation between FDG uptake and clinical stage, GLUT-1 expression, MIB-1 LI and histologic grading score was determined. No positive correlation was observed between FDG uptake and clinical stage (p=0.14). Intensity of GLUT-1 expression (r=0.76, p=0.001), MIB-1 LI (r=0.457, p=0.014) and histologic grading score (r=0.692, p=0.005) showed statistically significant positive correlations with FDG uptake. Stepwise logistic regression analysis revealed that expression of GLUT-1 transporters was the strongest parameter (r=0.760, p=0.0004) by which to predict positive FDG uptake. Therefore, glucose consumption, as determined by analysis of SUVs in FDG-PET, may be a noninvasive biomarker for ovarian epithelial tumors.

Lumbar sympathetic nerve activity and hindquarter blood flow during REM sleep in rats.

The present study aimed to investigate the response of lumbar sympathetic nerve activity (LSNA) to the onset of rapid eye movement (REM) sleep and its contribution to the regulation of muscle blood flow during REM sleep in rats. Electrodes for the measurements of LSNA, electroencephalogram, electromyogram and electrocardiogram and a Doppler flow cuff for the measurements of blood flow in the common iliac and mesenteric arteries, also catheters for the measurements of systemic arterial and central venous pressures were implanted chronically. REM sleep resulted in a step increase in LSNA, by 22 +/- 9% (mean +/-S.E.M., P < 0.05), a reduction of iliac vascular conductance, by -16 +/- 3% (P < 0.05) and a gradual increase in systemic arterial pressure, reaching a maximum value of 8.1 +/- 2.0 mmHg (P < 0.05) at 89 s after onset of REM sleep, while mesenteric vascular conductance increased simultaneously by 5 +/- 2% (P < 0.05). There was a significant (Pearson's correlation coefficient = 0.94, P < 0.05) inverse linear relationship between LSNA and the iliac blood flow. Unilateral lumbar sympathectomy blunted the reduction of iliac blood flow induced by the onset of REM sleep. The present observations suggest that the onset of REM sleep appears to be associated with a vasodilation in viscera and a vasoconstriction in skeletal muscle, such that systemic arterial pressure increases during REM sleep in rats.

Incremental benefits of FDG positron emission tomography over CT alone for the preoperative staging of ovarian cancer.

OBJECTIVE: The purpose of this study was to determine whether the addition of positron emission tomography (PET) with the radiotracer FDG to cross-sectional imaging, such as CT, increases accuracy in the detection of tumor spread. SUBJECTS AND METHODS. Fifteen patients who were thought to have ovarian cancer on the basis of the results of physical examination, sonography findings, and level of serum cancer antigen 125 were enrolled over an 11-month period. After screening, patients underwent two imaging examinations-abdominopelvic CT and whole-body FDG PET- within 2 weeks before surgery. Also before surgery, staging accuracy was assessed separately using CT with or without FDG PET (which was based on modifications of the International Federation of Gynecology and Obstetrics [FIGO] criteria). The results of the histology and surgery findings were used to assess the accuracy of the scanning findings. RESULTS: Staging revealed stage III disease in seven patients (IIIC, n = 6; IIIB, n = 1), stage II in three (IIC, n = 2; IIB, n = 1), and stage I in five (IC, n = 3; IA, n = 2), according to the FIGO criteria. Although CT staging correlated with postoperative staging in eight (53%) of 15 patients, consensus evaluation of CT with FDG PET staging improved correlation with postoperative staging in 13 (87%) of 15 patients. CONCLUSION: The addition of FDG PET to CT increases accuracy in staging of ovarian cancer.

Establishment of a novel human ovarian cancer cell line with high anchorage-independent growth ability.

The acquisition of anchorage-independence is an important hallmark of malignant transformation and is thought to be one of the critical factors in the metastasis and dissemination of cancer. We describe here the establishment and characterization of a novel human ovarian cancer cell line, TAC3, which has high anchorage-independent growth ability. This cell line has unique growth properties. Whereas TAC3 cells grew in an adherent manner on collagen-coated dishes, they grew in a non-adherent manner on plain culture dishes. Stable exponential growth was observed under both adherent and non-adherent conditions. Western blot analysis indicated that TAC3 had both strong expression of Bcl-2 and detachment-induced activation of extracellular signal-regulated kinase (ERK), and it was suggested that the detachment-induced proliferation signal would join the mitogen-activated protein kinase (MAPK) cascade at the level of MAPK/ERK kinase (MEK). Pharmacologic MEK inhibitor U0126 inhibited the growth of TAC3; it was more effective with non-adherent cells than with adherent cells. The TAC3 cell line may therefore be a useful tool for the investigation of the mechanisms of anchorage-independence and for the development of new treatment strategies, such as signal therapy, in human ovarian cancer.

A phase I study of continuous administration of 5-fluorouracil/cisplatin in advanced uterine cervical cancer.

BACKGROUND: The aim of this study was to assess the toxicity of a neoadjuvant chemotherapy (NAC) regimen consisting of cisplatin (CDDP) and 5-fluorouracil (5-FU) through 24-hour intravenous continuous infusion on days 1-4 in a Phase I study. PATIENTS AND METHODS: Thirteen patients were recruited for this study. All patients were treated with a regimen consisting of CDDP and 5-FU through a 24-hour intravenous continuous infusion on days 1-4, followed by radical hysterectomy and/or radiation. Each initial dose of CDDP and 5-FU was 20 mg/m2/day and 750 mg/m2/day, respectively, for 4 days. RESULTS AND CONCLUSION: In the third step, seven patients were treated at 25 mg/m2 day CDDP and 1000 mg/m2/day 5-FU, respectively, for 4 days. One of seven patients showed Grade 4 thrombopenia. However, in this dose step, all the patients showed an objective response. Although maximum tolerated doses (MTDs) were not reached, we decided to stop the escalation and to recommend this level for the Phase II study.

Whole-body PET with FDG is useful for following up an ovarian cancer patient with only rising CA-125 levels within the normal range.

In April 2000, a 54-year-old woman underwent surgery for ovarian serous cell carcinoma (stage IIb). After initial treatment, the patient underwent a physical examination, ultrasound examination and measurement of serum CA-125 levels every month. Although neither diagnostic imaging (ultrasound and computed tomography) nor physical examination showed any evidence of recurrence, the CA-125 level rose slowly and continuously within the normal range. In March 2001, an increased accumulation of 18F-fluorodeoxyglucose (FDG) in the pelvic cavity was seen on a positron emission tomography (PET) scan obtained 2 weeks before a relapse of a malignant lesion was diagnosed by gadolinium-enhanced MRI (Gd-MRI). It is reasonable to suppose that FDG-PET is clinically useful for detecting an early, small region of relapsed ovarian cancer. Moreover, FDG-PET may be helpful for determining whether a patient who has a continuous rising CA-125 level within the normal range should be treated in the absence of relapse regions detected by conventional methods.