Prolonged Observation Period Research Articles

Thermal ablation for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism.

Many studies have been conducted on splenic thermal ablation for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism. In this article, we review the evolution and current status of radiofrequency and microwave ablation in the treatment of spleen diseases. All publications from 1990 to 2011 on radiofrequency and microwave ablation for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism were retrieved by searching PubMed. Thermal ablation in the spleen for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism can preserve part of the spleen and maintain splenic immunologic function. Thermal ablation for assisting hemostasis in partial splenectomy minimizes blood loss during operation. Thermal ablation for spleen trauma reduces the number of splenectomy and the amount of blood transfusion. Thermal ablation for splenic metastasis is minimally invasive and can be done under the guidance of an ultrasound, which helps shorten the recovery time. Thermal ablation for hypersplenism increases platelet (PLT) and white blood cell (WBC) counts and improves liver function. It also helps to maintain splenic immunologic function and even improves splenic immunologic function in the short-term. In conclusion, thermal ablative approaches are promising for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism. In order to improve therapeutic effects, directions for future studies may include standardized therapeutic indications, prolonged observation periods and enlarged sample sizes.

Effects of Pre- and Postconditioning on Arrhythmogenesis in the In Vivo Rat Model

The antiarrhythmic potential of postconditioning in in vivo models remains poorly defined. We compared the effects of pre- and postconditioning on ventricular arrhythmogenesis against controls with and without reperfusion. Wistar rats (n = 40, 269 ± 3 g) subjected to ischemia (30 minutes)--reperfusion (24 hours) were assigned to the following groups: (1) preconditioning (2 cycles), (2) postconditioning (6 cycles), or (3) no intervention and were compared with (4) nonreperfused infarcts and (5) sham-operated animals. Infarct size was measured, and arrhythmogenesis was evaluated with continuous telemetric electrocardiographic recording, heart rate variability indices, and monophasic action potentials (MAPs). During a 24-hour observation period, no differences in mortality were observed. Reperfusion decreased infarct size and ameliorated sympathetic activation during the late reperfusion phase. Preconditioning decreased infarct size by a further 35% (P = .0017), but only a marginal decrease (by 18%, P = .075) was noted after postconditioning. Preconditioning decreased arrhythmias during ischemia and early reperfusion, whereas postconditioning almost abolished them during the entire reperfusion period. No differences were noted in MAPs or in the magnitude of sympathetic activation between the 2 interventions. Compared to postconditioning, preconditioning affords more powerful cytoprotection, but both interventions exert antiarrhythmic actions. In the latter, these are mainly evident during the ischemic phase and continue during early reperfusion. Postconditioning markedly decreases reperfusion arrhythmias during a prolonged observation period. The mechanisms underlying the antiarrhythmic effects of pre- and postconditioning are likely different but remain elusive.

Parathyroid hormone [1-34] improves articular cartilage surface architecture and integration and subchondral bone reconstitution in osteochondral defects in vivo

The 1-34 amino acid segment of the parathyroid hormone (PTH [1-34]) mediates anabolic effects in chondrocytes and osteocytes. The aim of this study was to investigate whether systemic application of PTH [1-34] improves the repair of non-osteoarthritic, focal osteochondral defects invivo. Standardized cylindrical osteochondral defects were bilaterally created in the femoral trochlea of rabbits (n=8). Daily subcutaneous injections of 10μg PTH [1-34]/kg were given to the treatment group (n=4) for 6 weeks, controls (n=4) received saline. Articular cartilage repair was evaluated by macroscopic, biochemical, histological and immunohistochemical analyses. Reconstitution of the subchondral bone was assessed by micro-computed tomography. Effects of PTH [1-34] on synovial membrane, apoptosis, and expression of the PTH receptor (PTH1R) were determined. Systemic PTH [1-34] increased PTH1R expression on both, chondrocytes and osteocytes within the repair tissue. PTH [1-34] ameliorated the macro- and microscopic aspect of the cartilaginous repair tissue. It also enhanced the thickness of the subchondral bone plate and the microarchitecture of the subarticular spongiosa within the defects. No significant correlations were established between these coexistent processes. Apoptotic levels, synovial membrane, biochemical composition of the repair tissue, and type-I/II collagen immunoreactivity remained unaffected. PTH [1-34] emerges as a promising agent in the treatment of focal osteochondral defects as its systemic administration simultaneously stimulates articular cartilage and subchondral bone repair. Importantly, both time-dependent mechanisms of repair did not correlate significantly at this early time point and need to be followed over prolonged observation periods.

Dynamics of Tumor Hypoxia in Response to Patupilone and Ionizing Radiation

Tumor hypoxia is one of the most important parameters that determines treatment sensitivity and is mainly due to insufficient tumor angiogenesis. However, the local oxygen concentration in a tumor can also be shifted in response to different treatment modalities such as cytotoxic agents or ionizing radiation. Thus, combined treatment modalities including microtubule stabilizing agents could create an additional challenge for an effective treatment response due to treatment-induced shifts in tumor oxygenation. Tumor hypoxia was probed over a prolonged observation period in response to treatment with different cytotoxic agents, using a non-invasive bioluminescent ODD-Luc reporter system, in which part of the oxygen-dependent degradation (ODD) domain of HIF-1α is fused to luciferase. As demonstrated in vitro, this system not only detects hypoxia at an ambient oxygen concentration of 1% O2, but also discriminates low oxygen concentrations in the range from 0.2 to 1% O2. Treatment of A549 lung adenocarcinoma-derived tumor xenografts with the microtubule stabilizing agent patupilone resulted in a prolonged increase in tumor hypoxia, which could be used as marker for its antitumoral treatment response, while irradiation did not induce detectable changes in tumor hypoxia. Furthermore, despite patupilone-induced hypoxia, the potency of ionizing radiation (IR) was not reduced as part of a concomitant or adjuvant combined treatment modality.

Delayed reproductive dysfunction in female rats induced by early life exposure to low-dose diethylstilbestrol

A one-lifespan test was carried out to establish a test protocol for endocrine-disrupting chemicals (EDCs). Diethylstilbestrol was administered by oral gavage to neonatal rats at doses of 0.05, 0.5 and 5μg/kg/day for 5 days after birth. Abnormal estrous cycles were observed throughout the study in all females from the 5μg/kg group, and in 40% from the 0.5μg/kg group from 24 weeks of age. The conception rate of 12-week-old females in the 5μg/kg group was 0%, and that of the 23-week-old females in the 0.5μg/kg group was 33.3%. No effect of DES was observed at the first parturition in any group, except for the 5μg/kg group. However, litter size was significantly reduced in the 0.5μg/kg group at the second parturition. These results indicated that a prolonged period of observation of reproductive function is necessary to determine EDCs reliably.

Gross Nitrification and Denitrification in Alpine Grassland Ecosystems on the Tibetan Plateau

Nitrification and denitrification are key microbiological processes in the soil nitrogen cycle and are the main biological sources of N2O emissions from soils. In this work, we measured gross nitrification and denitrification rates of northern Tibet alpine grassland ecosystems during the growing season and evaluated the influence of soil environmental factors. The results showed that the soil inorganic nitrogen concentration and gross nitrification and denitrification rates of both alpine meadow and alpine steppe varied obviously across the season. During the growing season mean values of gross nitrification and denitrification rates of the alpine meadow site were 3.0 and 2.3 times greater than those of the alpine steppe site, respectively. Both gross nitrification and denitrification rates were not significantly correlated with the determined soil characteristics which include soil microbial biomass, inorganic nitrogen, and soil temperature, except that gross nitrification seemed associated with the microsite where soil moisture was higher. Our results demonstrate that soil moisture can explain partly the higher soil nitrogen (N) transformation rates in alpine meadow sites, but soil N transformation microorganisms and enzyme activities studies covering prolonged observation periods are still needed to clarify the key soil environmental factors that control gross nitrification and denitrification processes in alpine grassland ecosystems.

INDOLENT NONPROGRESSIVE MULTIFOCAL CHOROIDAL LESIONS

We present a case series of four patients with unilateral, nonprogressive, yellow or white choroidal lesions of unknown etiology. Four healthy patients were referred to an academic medical retina practice for unusual fundus findings in one eye only. Both eyes of all four patients underwent clinical examination and retinal imaging, including fluorescein angiography, indocyanine green imaging, and optical coherence tomography. The outcome of this series was based on the clinical course of these patients and the features of the retinal images. The differential diagnosis based on the clinical appearances for these unknown cases includes birdshot chorioretinopathy, lymphoma or reactive lymphoid hyperplasia, metastases, orbital and intraocular pseudotumor, and bacterial or fungal infection. Extensive workups for these clinical entities including HLA-A29, angiotensin-converting enzyme level and computed tomography of the chest, liver function testing, magnetic resonance imaging of the brain, and orbital ultrasound have remained negative. Clinical and imaging characteristics for the four patients include absence of intraocular inflammation, late staining of lesions on fluorescein angiography, and hypofluorescence of lesions on indocyanine green. Lesions were not visible in the retina or retinal pigment epithelium using time domain optical coherence tomography. However, enhanced depth imaging spectral-domain optical coherence tomography imaging available for one patient suggests that these lesions are localized to the choroid; further interpretation of this advanced imaging technique will likely prove useful in the future. The patients' clinical course has remained nonprogressive with no changes over a prolonged period of observation. These cases could represent atypical manifestations of known retinal disease diagnoses or variations of a new chorioretinal disease process.

Genetic Response to Lenalidomide in the Circulating Progenitor Cell Compartment of MDS Cohort. Preliminary Results of the Multicenter German LE-MON-5 Study

Abstract 1721 Introduction:LE-MON-5 is a multicenter German phase-II study to verify the safety of monotherapy with lenalidomide (LEN) in MDS patients (pts) with IPSS low or Int-1 and isolated del(5q). We report our cytogenetic results after a monitoring period of sixteen months since start of the trial. Methods:For sequential and frequent survey of LEN-treated pts we applied FISH on enriched CD34+ stem cells from peripheral blood (CD34+ pb) every 2–3 months using a panel of 8 to 13 probes. Karyotyping and FISH on bone marrow aspirates was performed at initial screening and every six months. The median number of analyzed metaphases was 25 (4–30) and FISH analyzing was based on 200 interphase nuclei. Results:We have already screened 94 pts and could confirm isolated del(5q) in 76 (81%). Due to our cytogenetic results demonstrating additional changes in 18/94 (19%) pts, these were registered as screening failures and thus excluded from the study. Until now cytogenetic follow-up data for 40 pts is available. After a median follow-up of 9 months (2–16 months) we have observed a significant impact of LEN on the reduction of the clone size (p < 0.05) by FISH-monitoring. Based on cytogenetic remission, we have separated the cohort into three groups: Fast responders (14/40 (35%) pts) showed a very rapid cytogenetic response to therapy with >50% reduction of 5q- clone size within two months. In the second group, the slow responders, we observed >50% reduction of clone size in 9/40 (22.5%) after > two months. However, two pts showed an increase of 5q- clone after 12 and 13 months respectively after initial response in the sense of a relapse. In the third group, the non responders, (11/34 (27.5%)) we could not observe any cytogenetic response during the as yet limited observation period. In six cases (15%) we detected a reduction of the 5q- clone during follow-up, but the emergence of additional aberrations were also observed such as: 1. trisomy 8 in 6.7% of metaphases after 8 months and is reduced to 3.6% after 12 months, 2. trisomy 4 in 6.7% of metaphases after 6 months and is disappeared after 12 months, followed by emergence of trisomy 8 in 8% of interphase cells, 3. finally, two cases showed loss of Y-chromosome after 4 months in 6% and 19% of CD34+ pb cells, respectively. In CD34+ pb cells of another case, trisomy 8 was detectable after two months in 3.5% of cells. All these new secondary abnormalities occurred in cells with normal chromosomes 5 and were slightly above or below our laboratory thresholds (3 times standard variation). In only one case, a new abnormality emerged in the 5q- clone: In this case additional del(20q) occurred after 2 months in 46% of CD34+ pb cells. In this case no reduction of 5q- cells after 4 months of treatment was observed. However, FISH analysis after 6 months of treatment showed a 14% reduction for both aberrations. To date we could not identify any pts who acquired complex anomalies while treated with LEN. Conclusion:FISH analysis of CD34+ pb cells allows a reliable frequent and relevant genetic monitoring of treatment response to LEN. Our results confirm the positive and rapid effects of LEN on clones with del(5q): Thus, already after 2 months, we could observe up to 90% reduction in the 5q- clone size in 35% of pts. In general, remission rates increased with duration of therapy. We suspect that trisomy 4, 8 and Y-loss are fluctuant “mini clones” without any clinical relevance. Inclusion of additional pts and prolonged observation period will help us to better evaluate the clinical response to LEN. Disclosures:Off Label Use: lenalidomide for MDS del(5q) provided by Celgene for this clinical study. Germing:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Braulke:Celgene: Honoraria, Research Funding. Schanz:Celgene: Honoraria, Research Funding. Giagounidis:Celgene: Honoraria. Götze:Celgene: Honoraria. Haase:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

Long-Term Follow-Up Analysis of HD9601 Trial Comparing ABVD Versus Stanford V Versus MOPP/EBV/CAD in Patients With Newly Diagnosed Advanced-Stage Hodgkin's Lymphoma: A Study From the Intergruppo Italiano Linfomi

The Intergruppo Italiano Linfomi HD9601 trial compared doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) versus doxorubicin, vinblastine, mechloretamine, vincristine, bleomycin, etoposide, and prednisone (Stanford V [StV]) versus the combination of mechlorethamine, vincristine, procarbazine, prednisone (MOPP) with epidoxorubicin, bleomycin, vinblastine (EBV), lomustine, doxorubicin, and vindesine (CAD) (MOPP/EBV/CAD [MEC]) for the initial treatment of advanced-stage Hodgkin's lymphoma to select which regimen would best support a reduced radiotherapy program (limited to two or fewer sites of either previous bulky or partially remitting disease). Superiority of ABVD and MEC to StV was demonstrated. We report analysis of long-term outcome and toxicity. Patients with stage IIB, III, or IV were randomly assigned among six cycles of ABVD, three cycles of StV, and six cycles of MEC; radiotherapy was administered in 76, 71, and 50 patients in the three arms, respectively. Currently, the median follow-up is 86 months; in the prolonged observation period, eight additional failures, including two relapses, both in the StV arm, and six additional deaths in complete response were recorded. The 10-year overall survival rates were 87%, 80%, and 78% for ABVD, MEC, and StV, respectively (P = .4). The 10-year failure-free survival was 75%, 74%, and 49% in the ABVD, MEC, and StV arms, respectively (P < .001). The 10-year disease-free survival of patients treated or not with radiotherapy (RT) showed no difference for ABVD or MEC (85% v 80% and 93% v 68%), and a statistically significant difference for StV (76% v 33%; P = .004). No significant long-term toxicity was recorded. The long-term analysis confirmed ABVD and MEC superiority to StV. The use of RT after StV was established as mandatory. ABVD is still to be considered as the standard treatment with a good balance between efficacy and toxicity.

Recurrent Respiratory Depression Associated with Fentanyl Transdermal Patch Gel Reservoir Ingestion

BackgroundOpioid abuse is common in the United States and is currently on the rise. Fentanyl transdermal patches (FTPs) have been on the market since 1991, and have recently become a popular source of opioids for abusers. There are currently two distinct FTP designs available on the market today; a gel reservoir system and a matrix construct. The gel reservoirs of FTPs contain massive amounts of fentanyl and are easily extractable for abuse. Ingesting the gel reservoir of an FTP is potentially lethal. Case SeriesIn this case series, 4 patients ingested the gel reservoir of an FTP and experienced severe and recurrent respiratory depression necessitating continuous naloxone infusions. All patients responded adequately to initial prehospital doses of naloxone (0.8–2 mg intravenous) but developed recurrent respiratory depression within 2 h of presentation to the hospital. ConclusionThe gel reservoir of an FTP contains massive amounts of fentanyl. Ingestion of the gel may cause severe and recurrent respiratory depression necessitating repeated naloxone boluses, continuous naloxone infusion, and a prolonged observation period.

First Record of Aplomado Falcon (Falco femoralis) for the West Indies

Abstract I report the first sighting of Aplomado Falcon (Falco femoralis) for Puerto Rico and all of the West Indies. I observed a single individual at Laguna Cartagena National Wildlife Refuge (southwestern Puerto Rico) on 15 January 2008; the individual stayed until 25 January 2008. Photographs establishing the bird's identity were obtained during prolonged periods of observation by several observers.

Reflexivity in midwifery research: The insider/outsider debate

Objective to explore the challenges of conducting an observational study of postnatal interactions, between midwives and women, when the researcher was a midwife observing in familiar midwifery settings. Background participant observation conducted by researchers who are themselves midwives raises questions regarding the influence of ‘identity’ and ‘insider’ knowledge on the conduct of such projects. The insider/outsider status of researchers has been explored in other disciplines, yet this is an area which is underdeveloped in the midwifery literature where few attempts have been made to subject this issue to sustained analysis. Design a qualitative study (investigating the provision of breast-feeding support in the first week after birth) provided the opportunity for reflexive exploration of the tensions faced by midwife researchers. Setting two maternity units in New South Wales, Australia. Participants participants included 40 midwives and 78 breast-feeding women. Findings possessing ‘insider’ midwifery knowledge was advantageous in the ‘getting in’ and ‘fitting in’ phases of this research study however unanticipated role ambiguity, and moral and ethical challenges, arose as a result of this ‘insider’ knowledge and status. Prolonged periods of observation challenged the midwife researcher's preconceived ideas and early decisions about the advantages and disadvantages of being an ‘insider’ or an ‘outsider’ in the research setting. Key conclusions reflexive analysis of insider/outsider experiences revealed the middle ground which participant observers tend to navigate. Whilst professional insider knowledge and status offered many advantages, especially at the first study setting, some of the inherent embodied, and socially constructed features of the ‘midwife’ observer role, were unanticipated. Cultural competence, in these observational study settings, translated into role ambiguity, and at times, culturally entrenched role expectations. Implications for practice midwifery observation of clinical practice, for research, or practice development purposes, requires a degree of juggling of insider knowledge to facilitate observation and analysis. Prior to conducting observations midwives should consider how best to occupy the middle ground between insider and outsider. Within the middle ground the midwife can draw on those aspects of ‘self’ required to negotiate respectful relationships with colleagues, whilst also ensuring the maintenance of an analytical degree of distancing.

The Interrelationships among albumin, nutrient intake, and inflammation in elderly recuperative care patients.

To examine the interrelationships among low serum albumin, nutritional depletion, and ongoing inflammation in older patients recovering from illness. A prospective cohort study. A transitional care unit (TCU) within a Department of Veterans Affairs hospital nursing home care unit. 275 older veterans (mean age=78.9 ± 7.5y, 99% male) admitted for recuperative care and rehabilitation. At admission and discharge (median LOS 24d, IQR 16 to 44d), each subject completed a comprehensive standardized evaluation including a nutritional assessment and measurement of serum albumin, C-reactive protein (CRP), interleukin-6 (IL-6) and its soluble receptor, and tumor necrosis factor-alpha (TNF-α) and its soluble receptors (sTNF-RI and II). Complete nutrient intake assessments (calorie counts) were performed daily. Both the discharge albumin and the change in albumin (discharge minus admission) were strongly and inversely correlated with various indicators of inflammation, particularly CRP and IL-6. Change in CRP was the strongest correlate of change in albumin (R2 = 0.21, P<.001) and discharge IL-6 the strongest correlate of discharge albumin (R2 = 0.21, P<.001). Nutrient intake also correlated with albumin and its change, but entered the multivariable models after inflammatory indicators and explained a smaller portion of the variance. Although there were significant interactions between time and both nutrient intake and inflammation, the relative importance of inflammation as a potential determinant of the serum albumin concentration appeared to remain unchanged with longer periods of observation. Among elderly patients admitted to a TCU, inflammation appears to be a more powerful determinant of albumin and its change during the hospitalization than is nutrient intake. Further study is needed to prove causality and to determine whether the relative importance of inflammation on the albumin concentration diminishes with more prolonged periods of observation.

Further assessment of Mirazid as antischistosomal drug in experimental schistosomiasis hematobium

Conflicting reports are found in the literature about the efficacy of Mirazid® (MZ), which is a special formulation of myrrh obtained from the stem of Commiphora molmol (Nees), Engl. tree (Burseraceae), as an antischistosomal drug. This initiated the present study to further assess this drug in experimental schistosomiasis hematobium. The drug was administered orally to hamsters infected with Schistosoma hematobium () using 500 mg/kg body weight for six successive days on an empty stomach. The drug effect was examined after three periods: 4, 8 and 12 weeks post-treatment. Emphasis was given to certain parameters such as change in worm load, number of ova/mg tissue, oogram pattern and number of ova/g stool, and tegumental changes in the worms by electron microscopy after prolonged observation periods. The results showed very slight 3.4% worm reduction by MZ after the longest evaluation period (12 weeks), versus very high reduction (100%) by the reference drug praziquantel (PZQ). In comparison with the untreated control no change was found in the number of ova/mg tissue in MZ-treated hamsters regardless of the date of observation (4-12 weeks), versus significantly high reduction (99.6%) observed in the case of PZQ treatment. However, a significant decrease (22%) in the ratio of immature and increase in dead ova in tissues of MZ-treated hamsters was obvious at 12 weeks post treatment. In MZ-treated animals, a slight reduction (18.3%) in the number of stool eggs versus absence of eggs in PZQ-treated animals 12 weeks after treatment. Scanning electron microscopic examination of S. hematobium worms revealed intact tubercles, spines and sensory bulbs and no effect of the ventral side after MZ treatment. Meanwhile, PZQ treatment revealed extensive disruption of the tegument worm. Therefore, this experimental study gives extra support to previously reported negative evaluation about the effectiveness of this drug in the treatment of schistosomiasis against many other published positive results. This controversy about the efficacy of MZ may be attributed to inconsistency of its material which is obtained from natural origin.

202. Transgene Expression over a Prolonged Observation Period after bFGF Gene Therapy To Promote Healing of Injured Flexor Tendons

202. Transgene Expression over a Prolonged Observation Period after bFGF Gene Therapy To Promote Healing of Injured Flexor Tendons

Lack of Bone Neoplasms and Persistence of Bone Efficacy in Cynomolgus Macaques After Long-Term Treatment With Teriparatide [rhPTH(1-34)

In rats, teriparatide [rhPTH(1-34)] causes marked increases in bone mass and osteosarcoma. In primates, teriparatide causes lesser increases in bone mass, and osteosarcomas have not been reported. Previous studies in primates were not designed to detect bone tumors and did not include a prolonged post-treatment observation period to determine whether tumors would arise after cessation of treatment. Ovariectomized (OVX), skeletally mature, cynomolgus monkeys (n = 30 per group) were given teriparatide for 18 mo at either 0 or 5 microg/kg/d subcutaneously. After 18 mo of treatment, subgroups of six monkeys from both groups were killed and evaluated, whereas all remaining monkeys entered a 3-yr observation period in which they did not receive teriparatide. Surveillance for bone tumors was accomplished with plain film radiographs, visual examination of the skeleton at necropsy, and histologic evaluation of multiple skeletal sites. Quantitative assessments of bone mass, architecture, and strength were also performed. After the 18-mo treatment period, vertebral BMD, BMC, and strength (ultimate load) were increased by 29%, 36%, and 52%, respectively, compared with OVX controls. Proximal femur BMD, BMC, and strength were also increased by 15%, 28% and 33%, respectively. After 3 yr without treatment, no differences in bone mass or strength at the vertebra were observed relative to OVX controls; however, the femoral neck showed significant persistence in stiffness (20%), BMC (14%), and trabecular BV/TV (53%), indicating a retention of teriparatide efficacy at the hip. Radiographs and histology did not identify any bone proliferative lesions or microscopic lesions of osteosarcoma at the end of the treatment or observation period. These data indicate that teriparatide did not induce bone proliferative lesions over a 4.5-yr interval of observation, including 18 mo of treatment and 3 yr of follow-up observation. Bone analyses confirmed that teriparatide caused increases in bone mass and strength, consistent with previous studies. During the withdrawal phase, beneficial effects of teriparatide treatment on the vertebra were lost; however, some of the beneficial effects on the proximal femur persisted for 3 yr after cessation of treatment. Although the lack of bone tumors in this study provides some additional reassurance regarding the safety of teriparatide for the primate skeleton, the small group size and other limitations of this, or any other animal study, limit the ability to draw definitive conclusions regarding the risk of bone tumor developments in patients.

Isoflavonoid Composition of a Callus Culture of the Relict Tree Maackia amurensis Rupr. et Maxim

Isoflavonoids, an interesting and restricted group of secondary metabolites of legumes, exhibit estrogenic, antiangiogenic, and anticancer activities and are now popular as dietary supplements. Plant cell cultures that possess an increased ability to synthesize these metabolites were examined. During the investigation, cell cultures of the Far Eastern relict tree Maackia amurensis (Leguminosae) were established. A selection of seed-derived cell aggregates yielded the callus line designated A-18. This culture produces 20 isoflavonoids, namely, the isoflavones genistein, daidzein, formononetin, calycosin, derrone, and pseudobaptigenin and their glycosylated conjugates genistin, 6''-O-malonylgenistin, ononin, 6''-O-malonylononin, daidzin, 3'-methoxydaidzin, 4'-O-beta-D-glucopyranosyldaidzin, 4'-O-beta-D-glucopyranosylgenistin, and 7-O-beta-D-glucopyranosylcalycosin; the pterocarpans maackiain and medicarpin and their glycosylated conjugates 6'-O-malonyl-3-O-beta-D-glucopyranosylmaackiain and 6'-O-malonyl-3-O-beta-D-glucopyranosylmedicarpin; and the new pterocarpan glucoside 6'-O-malonyl-3-O-beta-D-glucopyranosyl-6,6a-dehydromaackiain. These isoflavonoids, possessing a hepatoprotective activity, were stably produced by the A-18 calli for prolonged periods of observation.

Incidence and time of intraoperative vascular complications in head and neck microsurgery

Vascular occlusion is still the main reason for flap loss and occurs mostly within the first hours after performing anastomoses. Many surgeons still prefer to perform reconstruction and close the defect before starting to anastomose. The aim of this investigation was to find out if detection of early vascular occlusion is facilitated with a prolonged observation period. Between January 2000 and August of 2006, 350 consecutive free flap transfers for reconstruction in maxillofacial surgery were analyzed. In all flaps vascular anastomoses were performed prior to definite flap insertion. The flaps were controlled continuously during soft tissue or bony reconstruction until final wound closure at the neck. Complete operation time, ischemia time of the flap, and time from reperfusion to wound closure (direct pedicle observation time) were registered for each flap. In 350 flaps (138 radial forearm, 94 fibular, 53 ALT, 23 DCIA, 26 soleus perforator, 9 lateral arm, 5 lat. dorsi, and 2 scapular), operation time in average was 8.5 h, ischemia time varied between 78 and 139 min (average 104 min), and direct pedicle observation time of the flaps was 144 min in average (93-192 min). Four arteries and 2 veins showed immediate failure within 5 min after clamp removal, 10 arteries and 6 veins developed thromboses during the direct pedicle observation time. Out of these 16 vascular complications, 15 developed later than 15 min, 7 of them later than 30 min, and 2 of them later than 45 min. The overall complication rate including secondary revision of the pedicle was 16.8%, and an overall flap survival rate resulted in 95.4%. We conclude that microvascular anastomoses should be controlled for at least 45 min before definite wound closure. By performing anastomoses first and flap insertion second, this can be easily warranted.

Accuracy of DaTSCAN (123I‐ioflupane) SPECT in diagnosis of patients with clinically uncertain parkinsonism: 2‐Year follow‐up of an open‐label study

We previously reported on the role of dopamine transporter (DAT) SPECT in the workup of patients with clinically uncertain parkinsonian syndromes (CUPS). The findings of that study supported the use of SPECT imaging with DaTSCAN ((123)I-Ioflupane) for accurate diagnosis in this population. We report here the 2-year follow-up of the CUPS study, which aimed to validate the results of DaTSCAN imaging and to ascertain whether a second scan could minimize any residual diagnostic uncertainty among those with an inconclusive diagnosis. Eighty-five of 118 patients (72%) were available at follow-up. In 8 of 85 patients the neurologist was unable to provide a definite diagnosis (named as inconclusive). At follow-up, clinical diagnosis agreed with initial DaTSCAN SPECT results in 69 of 77 patients (90%) in whom a specific diagnosis was established. A second SPECT scan was performed if clinical diagnosis at follow-up differed to that suggested by the initial scan (n = 8) or was inconclusive (n = 8). Among 8 patients whose clinical diagnosis differed to DaTSCAN images, a second scan was performed in 6 (2 refused) and the results supported the final clinical diagnosis in 4. Follow-up DaTSCAN SPECT helped to establish a diagnosis in 7 of 8 patients (87.5%) with a previously inconclusive diagnosis. DaTSCAN imaging shows a high rate of agreement with clinical diagnosis after 2-years follow-up. A second scan at 2 years follow-up can reduce remaining diagnostic uncertainty that is present even after a prolonged period of observation.

Seasonal dynamic of gross nitrification and N2O emission at two tropical rainforest sites in Queensland, Australia

Combined measurements of nitrification activity and N2O emissions were performed in a lowland and a montane tropical rainforest ecosystem in NE-Australia over a 18 months period from October 2001 until May 2003. At both sites gross nitrification rates, measured by the BaPS technique, showed a strong seasonal pattern with significantly higher rates of gross nitrification during wet season conditions. Nitrification rates at the montane site (1.48 ± 0.24–18.75 ± 2.38 mg N kg−1 day−1) were found to be significantly higher than at the lowland site (1.65 ± 0.21–4.54 ± 0.27 mg N kg−1 day−1). The relationship between soil moisture and gross nitrification rates could be described best by O’Neill functions having a soil moisture optimum of nitrification at app. 65% WFPS. At the lowland site, for which continuous measurements of N2O emissions were available, nitrification was positively correlated with N2O emission. Nitrification contributed significantly to N2O formation during dry season (app.85%) but less (app. 30%) during wet season conditions. In average 0.19‰ of the N metabolized by nitrification was released as N2O. The N2O fraction loss for nitrification was positively correlated with changes in soil moisture and varied slightly between 0.15 and 0.22‰. Our results demonstrate that combined N2O emission and microbial N turnover studies covering prolonged observation periods are needed to clarify and quantify the role of the microbial processes nitrification and denitrification for annual N2O emissions from soils of terrestrial ecosystems.