A prospective observational study on the stress levels at the time of embryo transfer and pregnancy testing following in vitro fertilisation treatment: a comparison between women with different treatment outcomes.

OBJECTIVE: To ascertain whether stress biomarkers and psychological indices of stress may predict both conception and miscarriage rates in women undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI). DESIGN: Prospective observational study. SETTING: A university-affiliated tertiary hospital. POPULATION: Infertile women who were undergoing fresh or frozen IVF/ICSI cycles. METHODS: Women were recruited to (1) complete validated psychological questionnaires (visual analogue scale of stress, state-trait anxiety inventory, perceived stress scale, fertility problem inventory, Beck depression inventory, and general health questionnaire), at the time of embryo transfer (ET) and pregnancy testing (PT), and (2) provide saliva samples for α-amylase (sAA) measurement before and after ET and at PT. MAIN OUTCOME MEASURES: Women were grouped according to subsequent reproductive outcome; scores/levels of all tests were then compared between groups at each time-point. RESULTS: In all, 197 women completed the study, of which 92 conceived and 28 miscarried. The level of psychological stress, as measured by questionnaires, was highest at the time of PT, whereas the level of biological stress as measured by sAA level (IU/l) post-ET (1.8 × 105  ± 1.5 × 105 ) was significantly (P < 0.001) higher than pre-ET (1.2 × 105  ± 1.0 × 105 ) and at PT (1.0 × 105  ± 1.1 × 105 ). However, there was no difference in psychological scoring and in sAA levels between women who did or did not conceive and who had miscarried or had an ongoing pregnancy. CONCLUSIONS: The level of sAA is highest following ET, whereas psychological stress is highest at PT. However, neither stress level appeared to be of prognostic value in predicting conception or miscarriage. TWEETABLE ABSTRACT: Stress level fluctuated at different time-points, but it did not predict conception or miscarriage.

The association between serum uric acid and asymptomatic intracranial arterial stenosis in middle-aged Koreans.

BACKGROUND AND AIMS: Intracranial arterial stenosis (ICAS) is one of the most common causes of stroke, especially in Asians. Hyperuricemia has been associated with an increased risk of comorbidities such as metabolic syndrome or cardiovascular diseases. However, there are few studies focusing on the association between serum uric acid (SUA) levels and asymptomatic ICAS. The aim of this study was to explore the association between SUA and the prevalence of ICAS in middle-aged Korean health screening examinees. METHODS AND RESULTS: A cross-sectional study was performed on 9417 males and 7755 females who underwent a comprehensive health examination including transcranial Doppler (TCD) ultrasonography. The association of SUA and ICAS was analyzed using multivariate logistic regression. The prevalence of ICAS among the total examinee population was 3.55%. In females, the multivariate-adjusted odds ratio for ICAS was 1.52 (confidence interval 1.13-2.04) in the 3rd quartile of SUA and 1.45 (1.05-2.00) in the highest quartile, compared to the reference (P for trend 0.008). This trend was evident in all clinically relevant subgroups evaluated, including women with low inflammation status. SUA was not significantly associated with the prevalence of ICAS among males. In a sensitivity analysis, the multivariate-adjusted odds ratio of middle cerebral artery stenosis in females was 1.60 (1.09-2.37) in the highest quartile compared to the reference (P for trend 0.023). CONCLUSIONS: Higher SUA level was associated with increased risk of ICAS among middle-aged females but not males. A further cohort study is warranted to elucidate the effect of SUA on asymptomatic ICAS.

NO-releasing xanthine KMUP-1 bonded by simvastatin attenuates bleomycin-induced lung inflammation and delayed fibrosis.

BACKGROUND AND PURPOSE: Pulmonary fibrosis (PF) is a progressing lung injury initiated by pulmonary inflammation (PI). Bleomycin (BLM) is the most common pathogenesis of PF through early PI and extensive extracellular matrix deposition. This study is aimed to determine whether NO-releasing KMUP-1 inhibits PI and PF, and if so, the benefits of KMUP-1S resulted from simvastatin (SIM)-bonding to KMUP-1. EXPERIMENT APPROACH: C57BL/6 male mice were intra-tracheally administered BLM (4 U/kg) at day 0. KMUP-1 (1-5 mg/kg), KMUP-1S (2.5 mg/kg), SIM (5 mg/kg), Plus (KMUP-1 2.5 mg/kg + SIM 2.5 mg/kg), and clarithromycin (CAM, 10 mg/kg) were orally and daily administered for 7 and 28 days, respectively, to mice, sacrificed at day-7 and day-28 to isolate the lung tissues, for examining the inflammatory and fibrotic signaling and measuring the cell population and MMP-2/MMP-9 activity in broncholaveolar lavage fluid (BAL). KEY RESULTS: KMUP-1 and KUP-1S significantly decreased neutrophil counts in BAL fluid. Fibroblastic foci were histologically assessed by H&E and Masson's trichrome stain and treated with KMUP-1 and references. Lung tissues were determined the contents of collagen and the expressions of TGF-ß, α-SMA, HMGB1, CTGF, eNOS, p-eNOS, RhoA, Smad3, p-Smad3, MMP-2 and MMP-9 by Western blotting analyses, respectively. These changes areregulated by NO/cGMP and inhibited by various treatments. KMUP-1 and KMUP-1S predominantly prevented HMGB1/MMP-2 expression at day-7 and reduced TGF-ß/phosphorylated Smad3 and CTGF at day-28. CONCLUSIONS AND IMPLICATIONS: KMUP-1 and KMUP-S restore eNOS, inhibit iNOS/ROCKII/MMP-2/MMP-9, attenuate histologic collagen disposition and reduce BALF inflammatory cells, potentially useful for the treatment of BLM-lung PF.

Investigation of direct and indirect phonon-mediated bond excitation in α-RDX.

We evaluate whether lattice or internal phonons dominate the thermal excitation of the N-N bonds in α-cyclotrimethylene trinitramine (α-RDX) by computing the fractional contributions of phonon modes to the excitation of all atomic interactions. We derive a method to compute these contributions, which we call mode energy fractions, from the phonon eigenvectors and a splitting of the dynamical matrix. This enables identification of phonon modes that most strongly excite the N-N bonds that play a key role in molecular decomposition of α-RDX. Correlating these fractions with the mode populations and contributions to the specific heat and thermal conductivity, we analyze how thermal energy is distributed by phonons following a passing shock. Contrary to the common explanation that thermal energy is transferred to the N-N bonds indirectly, by internal phonons, we find that lattice phonons dominate this thermal energy transfer, implying that energy flow follows a direct route. We also comment on implications of these results for non-shock decomposition of α-RDX.

Menstrual disorders in a Paediatric and Adolescent Gynaecology Clinic: patient presentations and longitudinal outcomes.

OBJECTIVE. To study the presentations, diagnoses, and outcomes in adolescents with menstrual disorders. DESIGN. Prospective cohort study. SETTING. Paediatric and Adolescent Gynaecology Clinic, Hong Kong. PARTICIPANTS. A total of 577 adolescents aged 14 to 19 years. MAIN OUTCOME MEASURES. The presentations and diagnoses of adolescents with menstrual disorders were reviewed and their menstrual outcomes determined by a telephone survey. RESULTS. In all, 47% presented with menorrhagia, prolonged menstruation, and short menstrual cycles; 27% had secondary amenorrhoea, 12% had dysmenorrhoea, 11% had oligomenorrhoea, and 3% had primary amenorrhoea. Significant diagnoses included congenital genital tract anomalies, premature ovarian failure, anorexia nervosa, and polycystic ovarian syndrome. Polycystic ovarian syndrome was diagnosed in 16% of the cohort. In all, 24% of these 577 patients had abnormal menstrual cycles 4 years later. Direct logistic regression analysis indicated a cycle length of more than 35 days at presentation (adjusted odds ratio=2.8; 95% confidence interval, 1.8-4.5), previous diagnosis of polycystic ovarian syndrome (adjusted odds ratio=2.0; 95% confidence interval, 1.1-3.4), and current body mass index of 23 kg/m(2) or higher (adjusted odds ratio=1.8; 95% confidence interval, 1.0-3.0) were risk factors for persistently long menstrual cycle exceeding 35 days. Adolescents who were screened out with a definitive diagnosis after initial assessment were at low risk of persistently long menstrual cycles at follow-up (adjusted odds ratio=0.3; 95% confidence interval, 0.1-0.8). CONCLUSIONS. Adolescent menstrual disorders should not be ignored. Long cycle, diagnosis of polycystic ovarian syndrome at first consultation, and a current body mass index of 23 kg/m(2) or higher were statistically associated with persistent problems.

Clinical features, treatment, and outcome in 102 adult and pediatric patients with localized high-grade synovial sarcoma.

Background. There remains controversy on the routine use of chemotherapy in localized SS. Methods. The records of 87 adult (AP) and 15 pediatric (PP) patients with localized SS diagnosed between 1986 and 2007 at 2 centres in Toronto were reviewed. Results. Median age for AP and PP was 37.6 (range 15-76) and 14 (range 0.4-18) years, respectively. 65 (64%) patients had large tumours (>5 cm). All patients underwent en bloc surgical resection resulting in 94 (92.2%) negative and 8 (7.8%) microscopically positive surgical margins. 72 (82.8%) AP and 8 (53%) PP received radiotherapy. Chemotherapy was administered to 12 (13.8%) AP and 13 (87%) PP. 10 AP and 5 PP were evaluable for response to neoadjuvant chemotherapy, with response rate of 10% and 40%, respectively. 5-year EFS and OS was 69.3 ± 4.8% and 80.3 ± 4.3%, respectively, and was similar for AP and PP, In patients with tumors >5 cm, in whom chemotherapy might be considered most appropriate, relapse occurred in 9/19 (47%) with chemotherapy, compared to 17/46 (37%) In those without. Conclusions. Patients with localized SS have a good chance of cure with surgery and RT. Evidence for a well-defined role of chemotherapy to improve survival In localized SS remains elusive.

Lymph node growth rate in testicular germ cell tumours: implications for computed tomography surveillance frequency.

AIM: To estimate the growth rate of lymph nodes in patients on surveillance for testicular cancer who developed recurrent disease. MATERIALS AND METHODS: During a 7-year period, 318 patients at our institution were managed by surveillance and 39 relapsed (12.3%). The computed tomography scans of 28 patients (median age 32 years; range 19-51 years) who met our inclusion criteria and who developed recurrent disease in the abdomen/pelvis were retrospectively reviewed. Thirteen patients had non-seminoma and 15 had seminoma. To estimate the lymph node growth rate, the slope of lymph node size over time was calculated. RESULTS: The median length of time from orchiectomy to the recurrence computed tomography was 131 days (range 49-520) or about 4.4 months for non-seminoma patients and 373 days (range 129-675) or about 12.3 months for seminoma patients. The median size of the involved lymph node at final computed tomography for seminoma patients was 12 mm (range 9-31 mm) and for non-seminoma patients was 15 mm (range 10-56 mm). The median lymph node growth rate for patients with seminoma was 1.35 mm/month (range 0.62-4.56) and for patients with non-seminoma 2.99 mm/month (range 0.77-7.06); the difference in growth rates was statistically significant (P=0.029). CONCLUSIONS: There is a statistically significant faster growth rate of lymph nodes in patients with recurrent non-seminoma compared with patients with seminoma. This finding supports a more frequent computed tomography schedule during the first 2 years of surveillance in non-seminoma patients compared with seminoma patients.

Management and clinical outcome of acute basilar artery dissection.

BACKGROUND AND PURPOSE: There have been inconsistencies on the prognosis and controversies as to the proper management of acute basilar artery dissection. The aim of this study was to evaluate acute basilar artery dissection and its outcome after management. MATERIALS AND METHODS: A total of 21 patients (mean age, 53 years; range, 24-78 years) with acute basilar artery dissection were identified between January 2001 and October 2007. Clinical presentation, management, and outcomes were retrospectively evaluated. RESULTS: The patients presented with subarachnoid hemorrhage (n = 10), brain stem ischemia (n = 10), or stem compression sign (n = 1). Ruptured basilar artery dissections were treated by stent placement with coiling (n = 4), single stent placement (n = 3), or conservatively (n = 3). Of the patients treated with endovascular technique, 6 had favorable outcome (modified Rankin scale [mRS], 0-2) and the remaining patient, who was treated by single stent placement, died from rebleeding. All 3 conservatively managed patients experienced rebleeding, of whom 2 died and the other was moderately disabled. Unruptured basilar artery dissections were treated conservatively (n = 7) or by stent placement (n = 4). Of the patients with unruptured basilar artery dissection, 9 had favorable outcome and the remaining 2 patients, both of whom were conservatively managed, had poor outcome because of infarct progression. The group with the ruptured basilar artery dissection revealed a higher mortality rate than the group with the unruptured dissection (30% vs 0%). The group treated with endovascular means revealed more favorable outcome than the group that was treated with conservative measures (90.9% vs 50%). CONCLUSION: The ruptured basilar artery dissections were at high risk for rebleeding, resulting in a grave outcome. Stent placement with or without coiling may be considered to prevent rebleeding in ruptured basilar dissections and judiciously considered in unruptured dissections with signs of progressive brain stem ischemia.

A two isocenter IMRT technique with a controlled junction dose for long volume targets.

Most IMRT techniques have been designed to treat targets smaller than the field size of conventional linac accelerators. In order to overcome the field size restrictions in applying IMRT, we developed a two isocenter IMRT technique to treat long volume targets. The technique exploits an extended dose gradient throughout a junction region of 4-6 cm to minimize the impact of field match errors on a junction dose and manipulates the inverse planning and IMRT segments to fill in the dose gradient and achieve dose uniformity. Techniques for abutting both conventional fields with IMRT ('Static + IMRT') and IMRT fields ('IMRT + IMRT') using two separate isocenters have been developed. Five long volume sarcoma cases have been planned in Pinnacle (Philips, Madison, USA) using Elekta Synergy and Varian 2100EX linacs; two of the cases were clinically treated with this technique. Advantages were demonstrated with well-controlled junction target uniformity and tolerance to setup uncertainties. The junction target dose heterogeneity was controlled at a level of +/-5%; for 3 mm setup errors at the field edges, the junction target dose changed less than 5% and the dose sparing to organs at risk (OARs) was maintained. Film measurements confirmed the treatment planning results.

Correlation of ventricular asymmetry with metabolic asymmetry in frontotemporal dementia.

BACKGROUND AND PURPOSE: The clinical presentation of frontotemporal dementia (FTD) is often asymmetrical in terms of both its clinical features and atrophy on MRI. Asymmetry in the lateral ventricle size on structural neuroimaging in FTD patients may have clinical significance. However, this has not been systematically investigated yet. This study compares the ventricular asymmetry seen on MRI with that of the asymmetric glucose metabolism using FDG-PET in patients with FTD. METHODS: Nineteen FTD patients who underwent both brain MRI and FDG-PET were retrospectively selected. As control groups, 23 and 11 age and sex-matched healthy normal subjects underwent either brain MRI or FDG-PET, respectively. The ventricular asymmetry index (VAI) was obtained in two ways: by visual rating (VAI-V) and by measuring the lateral ventricular volumes (VAI-ROI). The hemispheric asymmetry of the glucose metabolism on FDG-PET (MAI) was assessed in three ways: 1) by visual rating (MAI-V), 2) by counting the FDG activity of each hemisphere on normalized and smoothed PET images (MAI-ROI) and 3) by counting the number of voxels with significant hypometabolism based on statistical parametric mapping results (MAI-SPM). RESULTS: The VAIs on MRI (VAI-V and VAI-ROI) were highly correlated, as were the MAIs (MAI-V, MAI-ROI, and MAI-SPM) on FDG-PET. More importantly, the VAIs on MRI and the MAIs on FDG-PET showed high correlation. CONCLUSIONS: Ventricular asymmetry in FTD patients was common (78.9%) and there was a high correlation between the ventricular structural asymmetry and the hemispheric metabolic asymmetry. Therefore, it would be reasonable to interpret that the hemisphere with larger ventricle on MRI in FTD patients is undergoing a more active degenerative process.

Invasive pneumococcal infections: a clinical and microbiological analysis of 53 patients in Taiwan.

OBJECTIVE: To track penicillin susceptibility among Streptococcus pneumoniae causing invasive diseases and to evaluate risk factors for antibiotic resistance. METHODS: A retrospective study was performed in a medical center of all patients with invasive pneumococcal infections based on positive microbiological findings, confirmed by appropriate clinical and laboratory findings. MICs of penicillin and ceftriaxone were determined and interpreted by NCCLS methodology. RESULTS: Fifty-three episodes of invasive S. pneumoniae infections (ISPI) among 22 children and 31 adults were identified. The disease patterns of ISPI were similar between children and adults, and the most common modes were pneumonia (70%) and primary bacteremia (23%). The rate of penicillin-nonsusceptible S. pneumoniae (PNSP) isolated from pediatric patients was higher than that in adult patients (95.5% vs. 54.8%, P < 0.001). This finding was correlated to prior antibiotic use that was more common in children (36.4%) than in adults (18.9%). The rate of penicillin-resistance among S. pneumoniae isolates (PRSP) was extremely high in this area: 45.5% from pediatric patients and 41.9% from adult patients. More adults (90.3%) with ISPI had major underlying diseases than children (4.5%). This may explain why adult patients tended to run an unfavorable outcome (mortality rate, 51.6% and 4.5% in adults and children, respectively), although most of the cases with empyema were children. None of the patients enrolled in this study received pneumococcal vaccination. CONCLUSION: We suggest that vaccines be administered for young children and the elderly with major underlying diseases to prevent ISPI.

Nonconvulsive status epilepticus presenting as a subacute progressive aphasia.

We report a 62-year-old man with non-convulsive status epilepticus (NCSE) presenting as a progressive aphasia that developed insidiously over 5 weeks. On video-EEG monitoring, aggravation of the aphasia coincided with occurrence of seizure activities arising from the left fronto-temporal area. Brain MRI was noncontributory but a fluorodeoxyglucose-PET scan revealed a hypometabolism in the left anterior temporal area. Following anticonvulsant treatment, aphasia recovered gradually over several weeks despite prompt resolution of epileptic discharges on EEG. Our patient's findings, gradual onset of isolated aphasia with gradual resolution after initiation of treatment, may differ from previously reported cases with aphasic status epilepticus because their aphasia showed abrupt onset and rapid resolution with anticonvulsant medication.

Duration of enterovirus shedding in stool.

Excretion of enterovirus (EV) may persist for months after an EV infection; the exact duration of excretion, however, is not yet known. Twelve children who were infected with EV between September 1998 and June 1999 were enrolled into this study. The patients included 4 boys and 8 girls, aged from 1 month to 5 years. Six patients were asked to join this virus isolation program, and the other 6 were followed-up regularly. Only 2 of the patients were infected with EV 71. To delineate the duration of EV shedding in each case, throat swabs for virus isolation were performed every 1 or 2 weeks for at least 1 month, and stools were analyzed for at least 2 months following the same schedule. After the infection, EV was identifiable in the throat in 4 patients for 1 to 2 weeks. Excretion of EV through stool was evidenced for up to 7 weeks in 6 patients, 8 weeks in 3, and 11 weeks in 1. In the 2 patients who failed to show up for follow-up visits from the 7th week, excretion of EV through stool was recorded for at least 7 weeks. Different serotypes of EV could be isolated from the same patient who was not experiencing febrile illness in 2 instances in a series of virus cultures. Coexistence of vaccine poliovirus and non-polio EV, both isolated from stool, was evidenced in 2 patients. Results from this study suggest that EV may not be identified from the throat 2 weeks after the infection, but its excretion through stool can persist for up to 11 weeks. This study also demonstrated that subclinical EV coinfection could occur, and that live vaccine poliovirus did not interfere with the invasion of other non-polio EV.

Comparison of enterovirus 71 and coxsackie-virus A16 clinical illnesses during the Taiwan enterovirus epidemic, 1998.

OBJECTIVES: To compare enterovirus 71 (EV 71) with coxsackievirus A16 (Cox A16) clinical illness in patients at Chang Gung Children's Hospital during Taiwan's enterovirus epidemic of 1998. METHODS: With the use of the immunofluorescence assay and neutralization test, 177 cases of EV 71 and 64 cases of Cox A16 illness were confirmed from April to September, 1998. The clinical signs and symptoms, complications and case fatality rates were compared. RESULTS: Three-fourths of the cases were younger than 3 years of age, and the ratio of males to females was 1.3 in the EV 71 group and 1.2 in the Cox A16 group. In the EV 71 group 120 (68%) cases were uncomplicated, including 94 cases of hand, foot and mouth disease and 15 cases of herpangina, and 57 (32%) cases had complications, including 13 (7.3%) cases of aseptic meningitis, 18 (10%) cases of encephalitis, 4 (2.3%) cases of polio-like syndrome, 8 (4.5%) cases of encephalomyelitis and 12 (6.8%) cases of fatal pulmonary edema. Fourteen (7.9%) patients died, including 12 cases of pulmonary edema and 2 cases of encephalitis; seven (4%) patients had sequelae. By contrast, 60 (94%) of the 64 cases of Cox A16 infection were uncomplicated and only 4 (6.3%) cases were complicated by aseptic meningitis; no fatalities or sequelae were observed. By multivariate analysis vomiting (P = 0.01) and fever higher than 39 degrees C plus lasting longer than 3 days (P = 0.02) were significantly more frequent in the EV 71 group. CONCLUSION: EV 71 illness is more severe with significantly greater frequency of serious complications and fatality than is illness caused by Cox A16.