Search for Antideuterons of Cosmic Origin Using the BESS-Polar II Magnetic-Rigidity Spectrometer.

We searched for antideuterons (d[over ¯]'s) in the 4.7×10^{9} cosmic-ray events observed during the BESS-Polar II flight at solar minimum in 2007-2008 but found no candidates. The resulting 95% C.L. upper limit on the d[over ¯] flux is 6.7×10^{-5} (m^{2} s sr GeV/n)^{-1} in an energy range from 0.163 to 1.100 GeV/n. The result has improved by more than a factor of 14 from the upper limit of BESS97, which had a potential comparable to that of BESS-Polar II in the search for cosmic-origin d[over ¯]'s and was conducted during the former solar minimum. The upper limit of d[over ¯] flux from BESS-Polar II is the first result achieving the sensitivity to constrain the latest theoretical predictions.

Infantile outcome at 3 years of age among monochorionic twins with Type-II or -III selective fetal growth restriction with isolated oligohydramnios who underwent fetoscopic laser photocoagulation.

OBJECTIVE: This study aimed to examine infantile outcomes at 3 years of age with selective fetal growth restriction (sFGR) Types II and III with isolated oligohydramnios who underwent fetoscopic laser photocoagulation (FLP). METHODS: This multicenter prospective cohort study included monochorionic diamniotic twins who underwent FLP for sFGR between 16 and 25 weeks of gestation. The indication for performing FLP was in cases of sFGR Type II or III with oligohydramnios, where the maximal vertical pocket was ≤2 cm among twins with FGR. This was done in the absence of a typical twin-twin transfusion syndrome diagnosis. The primary outcome was the intact survival (IS) rate of infants at the corrected age of 40 weeks and 3 years. IS at the corrected age of 40 weeks was defined as survival without grade III or IV intraventricular hemorrhage or cystic periventricular leukomalacia, and IS at 3 years of age was defined as survival without neurodevelopmental morbidity, including cerebral palsy, neurodevelopmental impairment with a total developmental quotient of ≤70, bilateral deafness, or bilateral blindness. RESULTS: Among 45 patients with sFGR, 30 (66.7%) were classified as having Type II and 15 (33.3%) as Type III sFGR. The prevalence of IS at the corrected age of 40 weeks was 51.1% (n=23) in FGR twins and 95.5% (n=42) in larger twins. The prevalence of IS at 3 years of age was 46.7% (n=21) in FGR twins and 86.4% (n=38) in larger twins. Among the 24 FGR twins who were not diagnosed with IS at 3 years of age, 91.7% (22 of 24 cases) suffered fetal or infantile demise other than miscarriage and neurodevelopmental impairment. All larger twins who were not diagnosed with IS at 3 years of age (n=6, 13.6%) had neurological morbidity, in addition to one case of miscarriage. CONCLUSIONS: FGR twins and larger twins, when subjected to FLP due to sFGR coupled with umbilical artery Doppler abnormalities and isolated oligohydramnios, exhibit low rates of neurological morbidity and low mortality, respectively. Therefore, FLP for Type II or III sFGR with oligohydramnios may be a feasible and preferable management option. This article is protected by copyright. All rights reserved.

Inhibition of choroidal fibrovascular membrane formation by new class of RNA interference therapeutic agent targeting periostin.

Age-related macular degeneration (AMD) is a vision-threatening disease characterized by choroidal fibrovascular membrane (FVM) formation, choroidal neovascularization (CNV) and choroidal fibrosis. No safe and effective therapeutic method has been developed for the choroidal fibrosis, although anti-vascular endothelial growth factor therapy can partially shrink the CNV. We recently reported that periostin (POSTN), which is produced by retinal pigment epithelial cells, has an important role in the formation of preretinal FVMs, but its role in choroidal FVMs has not been determined. In this study, we used Postn knockout mice to investigate the role played by POSTN in choroidal FVM formation. In addition, we used a new class of RNA interference (RNAi) agent (NK0144) that targets POSTN and determined its effect on choroidal FVM development. Genetic ablation of Postn had an inhibitory effect not only on CNV formation but also on choroidal fibrosis in a mouse CNV model. NK0144 also had a greater inhibitory effect on both the CNV and choroidal fibrosis than control RNAi with no apparent adverse effects. These findings suggest a causal relationship between POSTN and choroidal FVM formation, and also a potential therapeutic role of intravitreal NK0144 for AMD.

Measurement of the cosmic-ray antiproton spectrum at solar minimum with a long-duration balloon flight over antarctica.

The energy spectrum of cosmic-ray antiprotons (p's) from 0.17 to 3.5 GeV has been measured using 7886 p's detected by BESS-Polar II during a long-duration flight over Antarctica near solar minimum in December 2007 and January 2008. This shows good consistency with secondary p calculations. Cosmologically primary p's have been investigated by comparing measured and calculated p spectra. BESS-Polar II data show no evidence of primary p's from the evaporation of primordial black holes.

Search for antihelium with the BESS-Polar spectrometer.

In two long-duration balloon flights over Antarctica, the Balloon-borne Experiment with a Superconducting Spectrometer (BESS) collaboration has searched for antihelium in the cosmic radiation with the highest sensitivity reported. BESS-Polar I flew in 2004, observing for 8.5 days. BESS-Polar II flew in 2007-2008, observing for 24.5 days. No antihelium candidate was found in BESS-Polar I data among 8.4×10(6) |Z|=2 nuclei from 1.0 to 20 GV or in BESS-Polar II data among 4.0×10(7) |Z|=2 nuclei from 1.0 to 14 GV. Assuming antihelium to have the same spectral shape as helium, a 95% confidence upper limit to the possible abundance of antihelium relative to helium of 6.9×10(-8)} was determined combining all BESS data, including the two BESS-Polar flights. With no assumed antihelium spectrum and a weighted average of the lowest antihelium efficiencies for each flight, an upper limit of 1.0×10(-7) from 1.6 to 14 GV was determined for the combined BESS-Polar data. Under both antihelium spectral assumptions, these are the lowest limits obtained to date.

Feasibility of duodenal balloon-assisted direct cholangioscopy with an ultrathin upper endoscope.

BACKGROUND AND STUDY AIMS: We have previously developed duodenal balloon-assisted direct cholangioscopy (DBA-DC) with an ultrathin endoscope (UTE). Here, we further evaluated the feasibility, safety, and diagnostic and therapeutic usefulness of DBA-DC using UTE. PATIENTS AND METHODS: 40 consecutive patients with biliary diseases were enrolled in a prospective observational feasibility study. We assessed the success rate, procedure time, durability of the UTE, and usefulness in diagnosis and therapy. We also evaluated safety, including cardiovascular alterations and biliary injury as complications of the procedure. RESULTS: DBA-DC was performed successfully in 37/40 patients (92.5%). The mean time to reach either biliary bifurcation or stricture was 11.8 ± 6.3 minutes. The procedure revealed 26 biliary stones, 5 cholangiocarcinomas, and 3 benign biliary strictures. Therapeutic procedures were performed in 16 patients (10 biliary lithotomies, 3 holmium-YAG laser lithotripsies, and 3 intraductal stent placements). No significant clinical complications related to DBA-DC were observed. Changes in cardiovascular responses and biliary biochemical parameters were minimal, except for leukocytosis in 8 patients. CONCLUSIONS: DBA-DC appears to be sufficiently feasible and may be useful as an alternative technique in cases that elude successful diagnosis and/or therapy with conventional endoscopic retrograde cholangiopancreatography (ERCP).

Prospective randomised comparative study of visual foam sclerotherapy alone or in combination with ultrasound-guided foam sclerotherapy for treatment of superficial venous insufficiency: preliminary report.

OBJECTIVE: The aim of the study is to compare ultrasound-guided foam sclerotherapy (UGFS: injection of foam sclerosant under ultrasound guidance) of the great saphenous vein (GSV) combined with visual foam sclerotherapy (VFS: injection of foam sclerosant under visual control) for varicose tributary veins and VFS alone in the treatment of GSV reflux. DESIGN AND METHODS: A total of 133 limbs in 97 patients with GSV reflux were randomised to receive either VFS alone or VFS combined with UGFS. In both groups, 1% polidocanol foam was used. Assessments included duplex ultrasonography, evaluation of Venous Clinical Severity Scores (VCSS) and CEAP (clinical, etiologic, anatomic, and pathophysiologic) scores. Ultrasonographic inspection of the foam in the GSV was carried out during 5 min before compression was applied. The primary 'end' point of the study was obliteration of the GSV at 6 months. RESULTS: A total of 51 limbs in 48 patients were treated with UGFS + VFS and the remaining 52 limbs in 49 patients were treated with VFS alone. There were no significant inter-group differences in patient age, male: female ratio, height, weight, body mass index, CEAP clinical scores or VCSS. The GSV diameter was 6.0 ± 1.7 mm (median ± interquartile range) in the UGFS + VFS group and 5.7 ± 1.6 mm in the VFS group (p = 0.419). The mean injected volume of foam for varicose tributary veins was 4 ± 2 ml in the UGFS + VFS group and 6 ± 2 ml in the VFS group, a significantly higher amount of foam being used in the latter (p < 0.001). However, the mean total amount of foam was greater in limbs treated with UFGS + VFS than in those treated with VFS alone (p = 0.017). Ultrasonographic inspection revealed complete vasospasm of the GSV in 37 (72.5%) limbs in the UGFS + VFS group and 29 (55.8%) in the VFS group during sclerotherapy (p = 0.097). At 6-month follow-up, complete occlusion was found in 23 limbs (45.1%) treated with UGFS + VFS and in 22 limbs (42.3%) treated with VFS. The difference between the two groups was not significant (p = 0.775). Reflux was absent in 30 limbs (58.8%) treated with UGFS + VFS and in 37 (71.2%) treated with VFS (p = 0.190). There was no inter-group difference in post-treatment VCSS (p = 0.223). CONCLUSIONS: These results show that UGFS + VFS and VFS are equally effective for the treatment of GSV reflux, despite the lower volume of foam used for VFS alone.

Comparative risk of common peroneal nerve injury in far anteromedial portal drilling and transtibial drilling in anatomical double-bundle ACL reconstruction.

PURPOSE: The purpose of this study was to investigate the risk of common peroneal nerve injury in FM drilling as compared to transtibial drilling in anatomical double-bundle ACL reconstruction. METHODS: Ten cadaveric knees without ligament injury or significant arthritis were used for this study. Knees were secured at 90° and 120° of flexion. In transtibial drilling groups, a guide pin was drilled through either the anteromedial bundle (AMB) or posterolateral bundle (PLB) tibial insertion site to either the AMB or PLB femoral insertion site (tibial insertion site-femoral insertion site: AM-AM, PL-PL, PL-AM and AM-PL). In FM drilling groups (FM-AM and FM-PL),the pin was drilled at the AMB or PLB femoral insertion site through the FM. We measured the shortest distance between the point at which the pin ran through the lateral cortex of the femur and the ipsilateral common peroneal nerve at a knee flexion of 90° and 120°. RESULTS: At a knee flexion of 90°, the shortest mean distance to the common peroneal nerve was 15.3 mm in the FM-PL group, 13.4 mm in the FM-AM group, 27.9 mm in the PL-PL group, 30.8 mm in the AM-AM group, 37.8 mm in the PL-AM group and 29.5 mm in the AM-PL group. At a knee of flexion 120°, the mean distance was 17.3 mm in the FM-PL group, 18.1 mm in the FM-AM group, 32.2 mm in the PL-PL group, 36.6 mm in the AM-AM group, 38.0 mm in the PL-AM group and 35.2 mm in the AM-PL group. Significant differences were observed between 90° and 120° of knee flexion in the FM-AM, PL-PL, AM-AM and AM-PL groups (P < 0.05). Significant differences were observed at flex 90° between the FM-AM group and AM-AM group, and between the FM-AM group and PL-AM group. Significant differences were observed at flex 120° between the FM-AM group and AM-AM group, between the FM-AM group and PL-AM group and between the FM-PL group and AM-PL group. CONCLUSION: The distance to the peroneal nerve in FM drilling was significantly longer at 120° than at 90° of knee flexion. Therefore, the risk of peroneal injury using FM drilling should decrease at a higher angle of knee flexion.

Temporal Profiles of Symptom Scores After Palliative Radiotherapy for Bleeding Gastric Cancer With Adjustment for the Palliative Prognostic Index: An Exploratory Analysis of a Multicentre Prospective Observational Study (JROSG 17-3).

AIMS: Although palliative radiotherapy for gastric cancer may improve some symptoms, it may also have a negative impact due to its toxicity. We investigated whether symptoms improved after radiotherapy with adjustment for the Palliative Prognostic Index (PPI) considering that patients with limited survival tend to experience deterioration of symptoms. MATERIALS AND METHODS: This study was an exploratory analysis of the Japanese Radiation Oncology Study Group study (JROSG 17-3). We assessed six symptom scores (nausea, anorexia, fatigue, shortness of breath, pain at the irradiated area and distress) at registration and 2, 4 and 8 weeks thereafter. We tested whether symptoms linearly improved after adjusting for the baseline PPI. Shared parameter models were used to adjust for potential bias in missing data. RESULTS: The present study analysed all 55 patients enrolled in JROSG 17-3. With time from registration as the only explanatory variable in the model, a significant linear decrease was observed in shortness of breath, pain and distress (slopes, -0.26, -0.22 and -0.19, respectively). Given that the interaction terms (i.e. PPI × time) were not significantly associated with symptom scores in any of the six symptoms, only PPI was included as the main effect in the final multivariable models. After adjusting for the PPI, shortness of breath, pain and distress significantly improved (slope, -0.25, -0.19 and -0.17; P < 0.001, 0.002 and 0.047, respectively). An improvement in fatigue and distress was observed only in patients treated with a biologically effective dose ≤14.4 Gy. CONCLUSION: Shortness of breath, pain and distress improved after radiotherapy. Moreover, a higher PPI was significantly associated with higher symptom scores at all time points, including baseline. In contrast, PPI did not seem to influence the improvement of these symptoms. Regardless of the expected survival, patients receiving radiotherapy for gastric cancer can expect an improvement in shortness of breath, pain and distress over 8 weeks. Multiple-fraction radiotherapy might hamper the improvement in fatigue and distress by its toxicity or treatment burden.

Factors predicting development of post-thrombotic syndrome in patients with a first episode of deep vein thrombosis: preliminary report.

OBJECTIVE: To investigate the indicative parameters reflecting the progression of post-thrombotic syndrome (PTS) in patients with a first episode of deep vein thrombosis (DVT). DESIGN AND METHODS: The patients' initial risk factors were assessed at presentation. Venous occlusion, and reflux and reflux parameters were evaluated at 6 months using venous duplex scanning. Near-infrared spectroscopy (NIRS) was also used to measure calf muscle deoxygenated haemoglobin levels at 6 months. Clinical manifestations were categorised using the clinical, etiologic, anatomic and pathophysiologic (CEAP) classification for chronic venous insufficiency (CVI), and the patients were divided into those having no PTS (C(0-3S),E(s),A(s,d,p),P(r,o)) and those having PTS (C(4-6S),E(s),A(s,d,p),P(r,o)). RESULTS: Of the 121 patients evaluated, 25 (21%) developed PTS with a mean follow-up period of 66 months. At initial presentation, ilio-femoral DVT (odds ratio (OR) 3.4, 95% confidence interval (CI) 1.4-8.6) was associated with development of PTS. At 6 months, venous occlusion combined with reflux (OR 4.4, 95% CI 2.9-20.7), peak reflux velocity >29.7 cm s(-1) (OR 13.7, 95% CI 4.1-45.7) and mean reflux velocity >8.6 cm s(-1) (OR 4.4, 95% CI 1.5-12.9) in the popliteal vein detected by duplex scanning were strong predictors of PTS. NIRS-derived retention index >3.5 was the strongest predictor of PTS at 6 months (OR 67.4, 95% CI 14.3-318.1). CONCLUSIONS: Ilio-femoral DVT is associated with the development of PTS at initial presentation. By contrast, occlusion and reflux, high reflux velocity in the popliteal vein and increased NIRS-derived retention index are important time-course predictors of PTS progression.

Unsedated transnasal ultrathin esophagogastroduodenoscopy may provide better diagnostic performance in gastroesophageal reflux disease.

Transnasal ultrathin esophagogastroduodenoscopy (N-EGD) with less gagging reflexes under non-sedation is likely suitable for the diagnosis of gastroesophageal reflux disease (GERD), however, N-EGD might have drawbacks, including its low image resolution. Limited information is available regarding the diagnosability of N-EGD for GERD. We compared the utility and gagging reflexes of three different endoscopies, including N-EGD, ultrathin transoral EGD (UTO-EGD) and conventional oral EGD (CO-EGD), in the diagnosis of GERD. We performed screening endoscopy in 1580 patients (N-EGD n=727, UTO-EGD n=599, CO-EGD n=254) and compared the frequency distributions of the severity of reflux esophagitis, hiatus hernia, and Barrett's epithelium to estimate the diagnostic performance of each endoscopy. We also analyzed patients' tolerability of endoscopy by the subjective evaluation of gagging reflexes. In the diagnosis of reflux esophagitis and Barrett's epithelium, there was no significant difference in the frequency distributions of the severity of the diseases among three EGDs. However, the incidence of Barrett's epithelium was higher than that in the previous nationwide survey of GERD in Japan. The evaluated size of hiatus hernia was smaller in N-EGD than in two other peroral endoscopies. The size of hiatus hernia correlated significantly with severity of gagging reflexes that was also lowest when diagnosed with N-EGD. N-EGD had an equivalent performance in the diagnosis of reflux esophagitis and Barrett's epithelium compared with CO-EGD. Enlargement of hiatus hernia induced by gagging reflexes was minimal in N-EGD, resulting in its better performance in the diagnosis of Barrett's epithelium.

Advanced chronic venous insufficiency is associated with increased calf muscle deoxygenation.

OBJECTIVE: To determine the temporal relationship between changes in calf muscle deoxygenated haemoglobin (HHb) measured by near-infrared spectroscopy (NIRS) during light-intensity exercise and clinical stages of chronic venous insufficiency (CVI). DESIGN AND METHODS: Calf muscle HHb level was obtained in 168 limbs of 158 patients with various clinical stages of CVI. Clinical manifestations were categorised according to the CEAP classification (CEAP, clinical, etiological, anatomical and pathophysiological), and the patients were divided into two groups: early CVI (C(0-3),E(p)(,s),A(s)(,d,p),P(r)(,o)) and advanced CVI (C(4-6),E(p)(,s), A(s)(,d,p),P(r)(,o)). Calf venous blood-filling index (FI-HHb) was calculated on standing, then the calf venous ejection index (EI-HHb) was obtained after one tiptoe movement and the venous retention index (RI-HHb) after 10 tiptoe movements. RESULTS: A total of 116 limbs had early, and 52 had advanced CVI. FI and RI were significantly increased in patients with advanced CVI compared with those with early CVI (P = 0.003, 0.0001, respectively). Similarly, RI was significantly greater in patients who had superficial, combined with deep and/or perforator, insufficiency than in patients with superficial insufficiency alone (P = 0.002). RI showed the strongest correlation with duplex-derived peak reflux velocity in the popliteal vein (r = 0.78, P < 0.0001). Combination of an optimal cut-off point of 0.2 for FI and 2.9 for RI improved the ability to discriminate early from advanced CVI, with a sensitivity of 94% and a specificity of 86%. CONCLUSIONS: These results suggest that FI and RI, as measured by NIRS, may be promising parameters for discriminating early CVI from advanced CVI.

Cytokeratins 8 and 19 in the mouse placental development.

To investigate the expression and biological roles of cytokeratin 19 (K19) in development and in adult tissues, we inactivated the mouse K19 gene (Krt1-19) by inserting a bacterial beta-galactosidase gene (lacZ) by homologous recombination in embryonic stem cells, and established germ line mutant mice. Both heterozygous and homozygous mutant mice were viable, fertile, and appeared normal. By 7.5-8.0 days post coitum (dpc), heterozygous mutant embryos expressed lacZ in the notochordal plate and hindgut diverticulum, reflecting the fact that the notochord and the gut endoderm are derived from the axial mesoderm-originated cells. In the adult mutant, lacZ was expressed mainly in epithelial tissues. To investigate the possible functional cooperation and synergy between K19 and K8, we then constructed compound homozygous mutants, whose embryos died approximately 10 dpc. The lethality resulted from defects in the placenta where both K19 and K8 are normally expressed. As early as 9. 5 dpc, the compound mutant placenta had an excessive number of giant trophoblasts, but lacked proper labyrinthine trophoblast or spongiotrophoblast development, which apparently caused flooding of the maternal blood into the embryonic placenta. These results indicate that K19 and K8 cooperate in ensuring the normal development of placental tissues.

Great saphenous vein sparing surgery by angioscopic valvuloplasty combined with axial transposition of a competent tributary vein--5-year follow-up.

OBJECTIVE: To evaluate the efficacy and haemodynamic effects of great saphenous vein (GSV) sparing surgery--valvuloplasty combined with axial transposition of a competent tributary vein (A-VACT). MATERIALS AND METHODS: Eighty-five limbs in 74 patients with isolated GSV incompetence were selected for GSV sparing surgery. After angiographic valvuloplasty, the competent tributary vein was exposed and cut 1.5 cm distal to its insertion point on the GSV. The transected vein was anastomosed end-to-side to the GSV, which was ligated between the tributary insertion site and the anastomosis. Venous valve competence were screened by serial postoperative duplex examination, and venous haemodynamic changes were analyzed using venous filling index (VFI) measured by air plethysmograph pre- and postoperatively. The follow-up period was 5-years. RESULTS: Sixty-seven patients were included in whom 76 limbs were treated. There was a statistically significant reduction in the vein diameter at the SFJ after 5-years (0.83 S.D. 0.29 cm to 0.46 S.D. 0.12 cm, p=0.0002, Wilcoxon). Similarly, significant reduction was found in the GSV at the 5-year follow-up point (0.63 S.D. 0.19 cm to 0.39 S.D. 0.11 cm, p<0.0001, Wilcoxon). On the other hand, there was significant increase in the diameter of the competent tributary vein postoperatively (0.22 S.D. 0.13 cm to 0.31 S.D. 0.12 cm, p<0.0001, Wilcoxon). Duplex scanning demonstrated reflux at the SFJ in 12 limbs (16%). Similarly, in the GSV, venous reflux was found in 13 limbs (17%). Reflux in the transposed tributary vein was found in 20 limbs (26%). But only 7 limbs (9%) had minor varicose veins' recurrence. VFI remained normal during the follow-up examination. The preoperative VFI confirmed the presence of venous reflux, but there were significant improvement in the VFI values at all postoperative examinations. CONCLUSIONS: A-VACT procedure improves venous function, resolves varicose veins at 5-years follow-up as well as preserving the GSV for future grafting.

Presence of lower limb deep vein thrombosis and prognosis in patients with symptomatic pulmonary embolism: preliminary report.

OBJECTIVES: To investigate the presence of lower limb deep vein thrombosis (DVT) and prognosis in patients with symptomatic pulmonary embolism (PE). MATERIALS AND METHODS: A total of 203 consecutive referral patients with PE were included. The distribution of DVT was evaluated with compression ultrasound (CUS), and all patients were then followed for 12 months for investigation of recurrence of venous thromboembolism (VTE) and fatal events as adverse outcome. RESULTS: The mean age of the patients was 62.8 years, and 78 (38.4%) were males. DVT was found in 118 (58.1%) patients. Of these patients, 61 (30.0%) had proximal DVT. Multivariate analysis demonstrated that active cancer, inadequate anticoagulation, leg symptoms, male gender, presence of DVT, presence of proximal DVT, and previous DVT were independent risk factors for adverse outcome. A clinical risk score ranging from 0 to 10 points was generated on the basis of multivariate regression coefficients. Receiver operating characteristic curve analysis showed that an appropriate cut-off point for discriminating between the presence and the absence of an adverse event was 4. Using this category, 166 (81.8%) patients were classified as low risk and 37 (18.2%) as high risk for adverse outcome. The adverse event rates were 6.0% for the low-risk group and 59.5% for the high-risk group. CONCLUSIONS: This study has confirmed the clinical significance of surveillance CUS in patients with a first episode of PE. Furthermore, a simple risk score on the basis of available variables can identify patients at risk of an adverse outcome in patients with PE.

Multiple small-dose injections can reduce the passage of sclerosant foam into deep veins during foam sclerotherapy for varicose veins.

OBJECTIVE: To compare the proportion of foam sclerosant that enters deep veins between multiple injections of <0.5 ml foam per injection and a few injections of >0.5 ml foam per injection. DESIGN & METHODS: One hundred and seven patients with superficial venous incompetence were randomised to receive either multiple injections of <0.5 ml 1% polidocanol (POL) -foam (multiple injections) or a few injections of >0.5 ml 1% POL-foam per injection (few injections) for the treatment of varicose tributaries. All patients then received ultrasound-guided foam sclerotherapy for refluxing great saphenous vein (GSV) using 3% POL-foam. Only a single session was allowed per patient in order to standardise treatment. Qualitative ultrasonographic inspection of the foam was carried out during a 5-min period before compression was applied. Post-sclerotherapy surveillance was done at day 3, 2 weeks, 1 month, 3 months, and 6 months. RESULTS: Fifty-six limbs in 53 patients were treated with multiple injections and the remaining 56 limbs in 54 patients were treated with a few injections. There were no significant differences in age or male:female ratio between the groups. The mean volume of 1% POL-foam was 2.2 S.D. 0.6 ml (range: 0.7-4.0 ml) in the multiple injections group and 2.5 S.D. 0.6 ml (range: 1.0-4.0 ml) in the few injections group (p=0.003). The mean volume of 3% POL was 1.5 ml (range: 0.7-3.0 ml) and 1.4 ml (range: 0.7-3.0 ml), respectively (p=0.137). Ultrasonographic inspection immediately after sclerotherapy demonstrated that foam was distributed significantly more commonly in the deep veins of patients treated with a few injections (p=0.0003). Two (4%) of the patients treated with a few injections developed migraine during the procedure, but recovered quickly with no further complications. There was no significant difference in the success rate between the groups at 6 months (p=0.257). CONCLUSIONS: These findings suggest that multiple small-dose injections can reduce the amount of foam sclerosant and the risk of foam sclerosant entering the deep veins in patients with superficial venous insufficiency.

Silicone-induced foreign-body reaction after first metatarsophalangeal joint arthroplasty for Jaccoud's arthropathy.

We report a case of Jaccoud's arthropathy with forefoot plantar callosity. The lesser toe metatarsal heads were resected and Swanson's double-stemmed flexible-hinge implant arthroplasty of the first metatarsophalangeal joint was performed. An osteolytic defect had formed around the implant after 2 years. Surgical revision comprised implant removal and synovectomy. Histology revealed a foreign-body reaction with birefringent material in multinucleated giant cells. Because the capsuloligamentous system is fragile in Jaccoud's arthropathy, we recommend resection arthroplasty or arthrodesis of the first MP joint as an initial operative approach.

High peak reflux velocity in the proximal deep veins is a strong predictor of advanced post-thrombotic sequelae.

BACKGROUND: The presence of reflux in the femoral vein (FV) and popliteal vein (POPV) after acute deep vein thrombosis (DVT) is considered to contribute to the development of advanced post-thrombotic syndrome (PTS). However, a quantification of reflux has yet to be determined. The purpose of study was to determine the indicative parameters reflecting the progression of PTS. METHODS: Venous abnormalities were evaluated in 131 limbs out of 130 patients who completed a six-year follow-up after an acute DVT. Clinical manifestations were categorized according to the clinical, etiologic, anatomic, and pathophysiologic (CEAP) classification, and the patients were divided into two groups at a six-year follow-up point: group I, C(0-3)E(s),A(s,d,p),P(r,o), early chronic venous insufficiency (CVI); group II, C(4-6)E(s),A(s,d,p),P(r,o), advanced CVI. Venous segments were examined whether they were occluded or recanalized. The reflux parameters assessed were the diameter (cm), the reflux time (RT; s), the peak reflux velocity (PRV; cm s(-1)), and total refluxed volume, and these parameters were assessed especially in the FV and POPV at the two-year (early phase) and subsequent six-year (late phase) follow-up points after DVT. RESULTS: There were 98 limbs in group I and 33 in group II. The frequency of venous reflux was significantly higher in group II (<0.0001). In contrast, the proportion of occlusion did not differ between the groups (P = 0.138). The proportions of FV and POPV incompetence were significantly higher in group II (P < 0.0001 and P < 0.0001, respectively). In these veins, the RT did not improve the discrimination power between the two groups. In contrast, the PRV had significant discrimination power in these veins at both the two- and six-year follow-up points. In the superficial venous system, there were no significant differences in any of the determined parameters between the groups. In group II, 19 patients (58%), who had early symptoms of CVI at the two-year follow-up point, subsequently developed advanced symptoms of PTS. After calculating a suitable cutoff point using receiver operating characteristic curves analysis at the two-year follow-up point, multivariable analysis showed that a PRV of >25.4 cm s(-1) in the POPV was the strongest independent predictor of advanced CVI [odds ratio (OR) 60.32; 95% confidence interval (95CI) 43.1-1238.97, P < 0.0001]. Similarly, in the FV, a PRV of >24.5 cm s(-1) was found to be a strong predictor of advanced CVI (OR 25.77, 95CI 10.56-331.12, P < 0.0001). CONCLUSIONS: These findings suggest that the presence of a high PRV in the proximal deep veins is an independent predictor of advanced symptoms of PTS.

The utility of quantitative calf muscle near-infrared spectroscopy in the follow-up of acute deep vein thrombosis.

BACKGROUND: To investigate patterns of venous insufficiency and changes in calf muscle deoxygenated hemoglobin (HHb) levels after an acute deep vein thrombosis (DVT). METHODS: A total of 78 limbs with an acute DVT involving 156 anatomic segments were evaluated with duplex scanning and near-infrared spectroscopy (NIRS) at 1, 3, 6 and 12 months. Venous segments were examined whether they were occluded, partially recanalized, and totally recanalized, and the development of venous reflux was noted. The NIRS was used to measure calf muscle HHb levels. Calf venous blood filling index (HHbFI) was calculated on standing, then the calf venous ejection index (HHbEI), and the venous retention index (HHbRI) were obtained after exercise. RESULTS: The segments investigated were the common femoral vein (CFV; 38 segments), femoral vein (FV; 37), popliteal vein (POPV; 44), and calf veins (CV; 37). At 1 year, thrombi had fully resolved in 67% of the segments, 27% remained partially recanalized, 6% were occluded. The venous occlusion was predominant in the FV (24%) at 1 year. On the contrary, rapid recanalization was obtained in CV than proximal veins at each examination (P < 0.01). Venous reflux was predominant in POPV (55%), followed by FV (19%), and no reflux was found in CV. At 1 year, the HHbFI in POPV reflux patients was significantly higher than those with resolution (0.19 +/- 0.14, 0.11 +/- 0.05 microm s, P = 0.009, respectively). Similarly, there was a significant difference in the HHbRI between the two groups (3.08 +/- 1.91, 1.42 +/- 1.56, P = 0.002, respectively). In patients with FV occlusion, the value of HHbRI was significantly higher than those with complete resolution (2.59 +/- 1.50, 1.42 +/- 1.56, P = 0.011, respectively). CONCLUSIONS: The lower extremity venous segments show different proportions of occlusion, partial recanalization, and total recanalization. The CV shows more rapid recanalization than proximal veins. The NIRS-derived HHbFI and HHbRI could be promising parameters as the overall venous function in the follow-up of acute DVT. These findings might be very helpful for physician in detecting patients who require much longer follow-up studies.

An archetypical extradiol-cleaving catecholic dioxygenase: the crystal structure of catechol 2,3-dioxygenase (metapyrocatechase) from Ppseudomonas putida mt-2.

BACKGROUND: Catechol dioxygenases catalyze the ring cleavage of catechol and its derivatives in either an intradiol or extradiol manner. These enzymes have a key role in the degradation of aromatic molecules in the environment by soil bacteria. Catechol 2, 3-dioxygenase catalyzes the incorporation of dioxygen into catechol and the extradiol ring cleavage to form 2-hydroxymuconate semialdehyde. Catechol 2,3-dioxygenase (metapyrocatechase, MPC) from Pseudomonas putida mt-2 was the first extradiol dioxygenase to be obtained in a pure form and has been studied extensively. The lack of an MPC structure has hampered the understanding of the general mechanism of extradiol dioxygenases. RESULTS: The three-dimensional structure of MPC has been determined at 2.8 A resolution by the multiple isomorphous replacement method. The enzyme is a homotetramer with each subunit folded into two similar domains. The structure of the MPC subunit resembles that of 2,3-dihydroxybiphenyl 1,2-dioxygenase, although there is low amino acid sequence identity between these enzymes. The active-site structure reveals a distorted tetrahedral Fe(II) site with three endogenous ligands (His153, His214 and Glu265), and an additional molecule that is most probably acetone. CONCLUSIONS: The present structure of MPC, combined with those of two 2,3-dihydroxybiphenyl 1,2-dioxygenases, reveals a conserved core region of the active site comprising three Fe(II) ligands (His153, His214 and Glu265), one tyrosine (Tyr255) and two histidine (His199 and His246) residues. The results suggest that extradiol dioxygenases employ a common mechanism to recognize the catechol ring moiety of various substrates and to activate dioxygen. One of the conserved histidine residues (His199) seems to have important roles in the catalytic cycle.