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Background: Reducing involuntary psychiatric admissions is a global concern. In Norway, the rate of involuntary admissions was 199 per 100,000 people 16 years and older in 2020. Individuals' paths towards involuntary psychiatric admissions usually unfold when they live in the community and referrals to such admissions are often initiated by primary health care professionals. Interventions at the primary health care level can therefore have the potential to prevent such admissions. Interventions developed specifically for this care level are, however, lacking. To enhance the quality and development of services in a way that meets stakeholders' needs and facilitates implementation to practice, involving both persons with lived experience and service providers in developing such interventions is requested., Aim: To develop a comprehensive intervention for primary mental health care aiming to prevent involuntary admissions of adults., Methods: This study had an action research approach with a participatory research design. Dialogue conferences with multiple stakeholders in five Norwegian municipalities, inductive thematic analysis of data material from the conferences, and a series of feedback meetings were conducted., Results: The co-creation process resulted in the development of the ReCoN (Reducing Coercion in Norway) intervention. This is a comprehensive intervention that includes six strategy areas: [1] Management, [2] Involving Persons with Lived Experience and Family Carers, [3] Competence Development, [4] Collaboration across Primary and Specialist Care Levels, [5] Collaboration within the Primary Care Level, and [6] Tailoring Individual Services. Each strategy area has two to four action areas with specified measures that constitute the practical actions or tasks that are believed to collectively impact the need for involuntary admissions., Conclusions: The ReCoN intervention has the potential for application to both national and international mental health services. The co-creation process with the full range of stakeholders ensures face validity, acceptability, and relevance. The effectiveness of the ReCoN intervention is currently being tested in a cluster randomised controlled trial. Given positive effects, the ReCoN intervention may impact individuals with a severe mental illness at risk of involuntary admissions, as more people may experience empowerment and autonomy instead of coercion in their recovery process., (© 2022. The Author(s).)

Objective: Whereas the correlation between diffuse slowing of EEG activity and neurodegenerative diseases such as Alzheimer's disease is well established, intermittent slowing over the temporal regions, which is a frequent finding in the elderly, does not have a specific clinical correlate. In this study, we compared quantitative EEG parameters between patients with temporal slowing with no signs of neurological disease and controls to evaluate cortical function in the temporal lobes and other cerebral regions. We also compared the width of the temporal lobes on magnetic resonance imaging (MRI)., Methods: Mean dominant frequency and relative power in delta, theta, alpha, and beta frequency bands were examined in 20 patients older than 60 years with intermittent temporal slowing and 20 age-matched controls without significant lesions on MRI or medical conditions known to affect the EEG. Furthermore, the correlation between the frequency of temporal slowing and the mean dominant frequency and the width of the medial temporal lobes on MRI were examined., Results: Mean dominant frequency and the relative power in the beta frequency band was lower in patients with temporal slowing than in controls in all of the cortical regions examined. No significant correlation was found between the frequency of slowing and the mean dominant frequency. There was no significant difference in the width of the medial temporal lobes., Conclusions: Intermittent temporal slowing was correlated with diffusely reduced mean dominant frequency and a shift in relative power to lower frequency bands., Significance: The results suggest that subclinical diffuse cerebral pathology may be present in subjects with intermittent temporal slowing, but prospective studies including tests of cognitive function, cerebral perfusion, metabolic status, and advanced neuroimaging should be conducted.

Warning systems with the ability to predict floods several days in advance have the potential to benefit tens of millions of people. Accordingly, large-scale streamflow prediction systems such as the Advanced Hydrologic Prediction Service or the Global Flood Awareness System are limited to coarse resolutions. This article presents a method for routing global runoff ensemble forecasts and global historical runoff generated by the European Centre for Medium-Range Weather Forecasts model using the Routing Application for Parallel computatIon of Discharge to produce high spatial resolution 15-day stream forecasts, approximate recurrence intervals, and warning points at locations where streamflow is predicted to exceed the recurrence interval thresholds. The processing method involves distributing the computations using computer clusters to facilitate processing of large watersheds with high-density stream networks. In addition, the Streamflow Prediction Tool web application was developed for visualizing analyzed results at both the regional level and at the reach level of high-density stream networks. The application formed part of the base hydrologic forecasting service available to the National Flood Interoperability Experiment and can potentially transform the nation's forecast ability by incorporating ensemble predictions at the nearly 2.7 million reaches of the National Hydrography Plus Version 2 Dataset into the national forecasting system.

Aims: Acute acalculous cholecystitis can be treated with percutaneous cholecystostomy in critically ill patients unfit for surgery. However, the evidence on the outcome is sparse. We conducted a retrospective analysis of acute acalculous cholecystitis patients treated with percutaneous cholecystostomy during a 10-year study period., Methods: An observational study of 56 consecutive patients treated with percutaneous cholecystostomy for acute acalculous cholecystitis was conducted in the period from 1 June 2002 to 31 May 2012. All data were obtained by review of medical records., Results: A total of 56 consecutive patients were treated with percutaneous cholecystostomy for acute acalculous cholecystitis. Six patients (10.7%) died within 30 days after the procedure. Percutaneous cholecystostomy could serve as a definitive treatment option in 45 patients (80.4%), whereas 1 patient (1.8%) required cholecystectomy due to recurrence of cholecystitis. Four patients (7.1%) were treated with percutaneous cholecystostomy as a bridging procedure to subsequent elective laparoscopic cholecystectomy within a median of 8.8 months (range: 7.7-33.4 months). There was no significant difference in the risk of cholecystitis recurrence between patients with (6/37) and without (2/3) contrast passage to the duodenum on cholangiography (p = 0.096)., Conclusion: Percutaneous cholecystostomy is successful as a definitive treatment option in the majority of patients with acute acalculous cholecystitis. It is associated with a low rate of mortality and subsequent cholecystectomy., (© The Finnish Surgical Society 2015.)

Background: Patients with cutaneous melanoma metastases have experienced excellent responses to intralesional interleukin (IL)-2. This has led to its recent inclusion into the US National Comprehensive Cancer Network guidelines for management of cutaneous melanoma metastases. Despite this, intralesional IL-2 has not been highlighted in the US literature nor have US physicians adopted it., Objective: We sought to evaluate the effectiveness of intralesional IL-2 combined with topical imiquimod and retinoid for treatment of cutaneous metastatic melanoma., Methods: A retrospective case series of 11 patients with cutaneous metastatic melanoma were treated with intralesional IL-2 combined with topical imiquimod and retinoid., Results: A 100% complete local response rate with long-term follow-up (average of 24 months) was seen in all 11 patients treated with this proposed regimen. Biopsy specimens of treated sites confirmed absence of malignant cells. The most common treatment-related adverse event was rigors., Limitations: Small number of patients, retrospective review of charts, and lack of a comparison group were limitations., Conclusion: Intralesional IL-2 administered concomitantly with topical imiquimod and a retinoid cream is a promising therapeutic option for managing cutaneous melanoma metastases. The regimen was well tolerated and should be considered as a reasonable alternative to surgical excision., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Percutaneous cholecystostomy (PC) can be used to treat patients with acute calculous cholecystitis (ACC) who are considered to be unfit for surgery. However, this procedure has been insufficiently investigated. This paper presents the results of a 10-year experience with this treatment modality., Methods: A retrospective observational study of all consecutive patients treated with PC for ACC in the period from 1 May 2002 to 30 April 2012 was conducted. All data were collected from patients' medical records., Results: A total of 278 patients were treated with PC for ACC. Of these, 13 (4.7%) died within 30 days, 28 (10.1%) underwent early laparoscopic cholecystectomy and three (1.1%) patients were lost from follow-up. Of the remaining 234 patients, 55 (23.5%) were readmitted for the recurrence of cholecystitis. In 128 (54.7%) patients, PC was the definitive treatment (median follow-up time: 5 years), whereas 51 (21.8%) patients were treated with elective laparoscopic cholecystectomy. The frequency of recurrence of cholecystitis in patients with contrast passage to the duodenum on cholangiography was lower than that in patients without contrast passage (21.1% versus 36.7%; P = 0.037)., Conclusions: The present study, which is the largest ever conducted in this treatment area, supports the hypothesis that PC is an effective treatment modality for critically ill patients with ACC unfit for surgery and results in a low rate of 30-day mortality., (© 2014 International Hepato-Pancreato-Biliary Association.)

Background: Despite effective local therapy with surgery and radiotherapy (RT), ~50 % of patients with high-grade soft tissue sarcoma (STS) will relapse and die of disease. Since experimental data suggest a significant synergistic effect when antiangiogenic targeted therapies such as sorafenib are combined with RT, we chose to evaluate preoperative combined modality sorafenib and conformal RT in a phase I/II trial among patients with extremity STS amenable to treatment with curative intent., Methods: For the phase I trial, eight patients with intermediate- or high-grade STS >5 cm in maximal dimension or low-grade STS >8 cm in maximal dimension received concomitant sorafenib (dose escalation cohort 1:200 twice daily, cohort 2:200/400 daily) and preoperative RT (50 Gy in 25 fractions). Sorafenib was continued during the entire period of RT as tolerated. Surgical resection was completed 4-6 weeks following completion of neoadjuvant sorafenib/RT. Three sorafenib dose levels were planned. Primary endpoints of the phase I trial were maximal tolerated dose and dose-limiting toxicity (DLT)., Results: Eight patients were enrolled in the phase I (five females, median age 44 years, two high-grade pleomorphic, two myxoid/round cell liposarcoma, four other). Median tumor size was 16 cm (range 8-29), and all tumors were located in the lower extremity. Two of five patients treated at dose level 2 developed DLT consisting of grade 3 rash not tolerating drug reintroduction. Other grade 3 side effects included anemia, perirectal abscess, and supraventricular tachycardia. Radiation toxicity (grade 1 or 2 dermatitis; N = 8) and post-surgical complications (three grade 3 wound complications) were comparable to historical controls and other series of preoperative RT monotherapy. Complete pathologic reponse (≥95 % tumor necrosis) was observed in three patients (38 %)., Conclusion: Neoadjuvant sorafenib in combination with RT is tolerable and appears to demonstrate activity in locally advanced extremity STS. Further study to determine efficacy at dose level 1 is warranted. (ClinicalTrials.gov identifier NCT00805727).

Purpose: Everolimus, an oral inhibitor of mammalian target of rapamycin, can augment the efficacy of HER inhibitors in preclinical studies. This study was conducted to determine the safety and pharmacokinetics (PK) of the combination of lapatinib, a Her1 and 2 inhibitor, and everolimus and to describe its anti-tumor activity in the Phase I setting., Methods: In Part I, dose escalation to define the maximum tolerated dose (MTD) was performed. In Part II, PK of both drugs were analyzed to assess drug-drug interaction., Results: Twenty-three evaluable patients with advanced cancers were treated on six different dose levels in Part I of the study. The dose-limiting toxicities were diarrhea, rash, mucositis, and fatigue. The MTD of the combination was 1,250 mg of lapatinib and 5 mg of everolimus once daily. In Part II of the study, 54 patients were treated with the combination at the MTD. The mean everolimus time to maximum concentration was increased by 44 %, and mean clearance was decreased by 25 % when co-administered with lapatinib, though these differences were not statistically significant. There was no significant influence on the PK of lapatinib by everolimus. Two patients achieved a partial response [thymic cancer (45+ months) and breast cancer (unconfirmed PR; 7 months)]; 11 patients attained stable disease of at least 4 months., Conclusions: Lapatinib and everolimus are well tolerated at doses of 1,250 and 5 mg po daily, respectively. Stable disease ≥4 months/PR was achieved in 13 of 78 patients (17 %).

Importance: Although prospective randomized data are available to guide the multidisciplinary management of soft tissue sarcoma (STS) of the extremities, controversy exists regarding adjuvant chemotherapy and radiation therapy., Objective: To determine if clinical specialty introduces bias in recommendations for multimodality treatment of STS., Design: Electronic survey., Setting: Database of active members of the American Society of Clinical Oncology, the Society of Surgical Oncology, and the Connective Tissue Oncology Society., Participants: Members of specialty oncology societies with an active interest in STS., Exposure: Physician specialty., Main Outcomes and Measures: Survey responses regarding the multidisciplinary management of STS were scored on a 5-point Likert scale and analyzed using analysis of variance., Results: The questionnaire was completed by 320 of 490 potential respondents (65%), including medical (18%), radiation (8%), orthopedic (22%), and surgical oncologists (45%). Respondents concurred on the use of radiation therapy for margins positive for tumor, for high-grade tumors, for improvement in local control, for tumors larger than 10 cm, and for tumors in close proximity to a neurovascular bundle. Respondents diverged on the use of radiation therapy for tumors 5 to 10 cm in size, for low-grade tumors, for radiation-associated STS, and for survival benefit. Only radiation oncologists felt that radiation therapy was underutilized as a treatment modality (mean [SEM] Likert scale score, 2.44 [0.12]; P < .001). There was agreement on the use of chemotherapy for synovial sarcoma, for high-grade tumors, for tumors larger than 10 cm, for patients younger than 50 years of age, and for survival benefit. Medical oncologists were more likely to recommend chemotherapy for margins positive for tumor (mean [SEM] score, 3.12 [0.12]; P = .03) and for improvement in local control (mean [SEM] score, 2.91 [0.12] P = .08). Surgical oncologists placed the least emphasis on chemotherapy in the overall treatment plan (mean [SEM] score, 2.60 [0.07]; P = .001)., Conclusions and Relevance: Specialty bias exists in adjuvant treatment recommendations for STS. This highlights the importance of multidisciplinary STS tumor boards and interdisciplinary care to facilitate consensus decision making for individual patients.

Background and Purpose: The potential adverse effects of static stretching on athletic performance are well documented, but still appears to be controversial, especially as they relates to sprinting. The prevalence of this practice is demonstrated by the number of competitive and recreational athletes who regularly engage in stretching immediately prior to sprinting with the mindset of optimizing their performance. The purpose of this study was to examine the effects of acute static, dynamic, and ballistic stretching, and no stretching of the iliopsoas muscle on 40-yard sprint times in 18-37 year-old non-competitive, recreational runners., Methods: Twenty-five healthy recreational runners (16 male and 9 female) between the ages of 24 and 35 (Mean = 26.76 yrs., SD = 2.42 yrs.) completed this study. A repeated measures design was used, which consisted of running a 40-yard sprint trial immediately following each of 4 different stretching conditions aimed at the iliopsoas muscle and lasting 1 minute each. The 4 conditions were completed in a randomized order within a 2-week time period, allowing 48-72 hours between each condition. Prior to each 40-yard sprint trial, a 5-minute walking warm-up was performed at 3.5 mph on a treadmill. The subject then ran a baseline 40-yard sprint. After a 10-minute self-paced walk, each subject performed one of the 4 stretching conditions (ballistic, dynamic, static, and no stretch) and then immediately ran a timed 40-yard sprint., Results: There was a significant interaction between stretching conditions and their effects on sprint times, F(3,72) = 9.422, p<.0005. To break down this interaction, simple main effects were performed with 2 repeated measures ANOVAs and 4 paired t-tests using a Bonferroni corrected alpha (α = .0083). There were no significant differences between the 4 pre-condition times, p = 0.103 (Greenhouse-Geisser) or the post-condition times, p = 0.029. In the no stretch condition, subjects improved significantly from pre- to post- sprint times (p<0.0005). There were no statistically significant differences in pre- and post-stretch condition sprint times among the static (p = 0.804), ballistic (p = 0.217), and dynamic (p = 0.022) stretching conditions., Conclusions: Sprint performance may show greatest improvement without stretching and through the use of a walking generalized warmup on a treadmill. These findings have clinically meaningful implications for runners who include iliopsoas muscle stretching as a component of the warm-up., Level of Evidence: Level 2.

Background: Genetic abnormalities in cell cycle control are common in malignant melanoma. UCN-01 (7-hydroxystaurosporine) is an investigational agent that exhibits antitumor activity by perturbing the cancer cell cycle. A patient with advanced melanoma experienced a partial response in a phase I trial of single agent UCN-01. We sought to determine the activity of UCN-01 against refractory metastatic melanoma in a phase II study. Patients and methods Patients with advanced melanoma received UCN-01 at 90 mg/m(2) over 3 h on cycle 1, reduced to 45 mg/m(2) over 3 h for subsequent cycles, every 21 days. Primary endpoint was tumor response. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). A two-stage (17 + 16), single arm phase II design was employed. A true response rate of ≥ 20% (i.e., at least one responder in the first stage, or at least four responders overall) was to be considered promising for further development of UCN-01 in this setting. Results Seventeen patients were accrued in the first stage. One patient was inevaluable for response. Four (24%) patients had stable disease, and 12 (71%) had disease progression. As there were no responders in the first stage, the study was closed to further accrual. Median PFS was 1.3 months (95% CI, 1.2-3.0) while median OS was 7.3 months (95% CI, 3.4-18.4). One-year and two year OS rates were 41% and 12%, respectively. A median of two cycles were delivered (range, 1-18). Grade 3 treatment-related toxicities include hyperglycemia (N = 2), fatigue (N = 1), and diarrhea (N = 1). One patient experienced grade 4 creatinine elevation and grade 4 anemia possibly due to UCN-01. No dose modification was required as these patients had disease progression. Conclusion Although well tolerated, UCN-01 as a single agent did not have sufficient clinical activity to warrant further study in refractory melanoma.

Wear and damage of ultrahigh molecular weight polyethylene (UHMWPE) tibial inserts used in total knee arthroplasty are accelerated by oxidation. Radiation crosslinking reduces wear but produces residual free radicals adversely affecting stability. One alternative to stabilize radiation-crosslinked UHMWPE is to infuse the material with vitamin E (vit E). We investigated the properties of 100-kGy e-beam-irradiated UHMWPE that was subsequently doped with vitamin E in comparison with conventional UHMWPE. Both polymers were sterilized with gamma irradiation in vacuum packaging. Vitamin E-doped UHMWPE showed lower wear before and after aging (2.4 ± 0.5 and 2.5 ± 0.8 mg/million cycle, respectively, vs 26.9 ± 3.5 and 40.8 ± 3.0 mg/million cycle for conventional UHMWPE). Conventional UHMWPE showed oxidation after accelerated aging, and its mechanical properties were adversely affected, whereas vit E-doped UHMWPE showed no oxidation or changes in its mechanical properties. Vitamin E stabilization of radiation-crosslinked UHMWPE resulted in low wear and high oxidation resistance; it is an alternative load-bearing material for total knee applications., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Sevoflurane post-conditioning (SePost) has been found to alleviate ischemic myocardial reperfusion injury through the activation of prosurvival kinases. Lowered myocardial oxygen demand from reduced cardiac work may also contribute to cardioprotection, and is much less well-studied. Our aim was to examine the simultaneous effects of SePost on cardiac work (here, rate-pressure product, RPP) and myocardial infarct size in a porcine model., Methods: Anesthetized 25 kg pigs were randomly allocated to two groups and underwent 45 min regional coronary artery balloon occlusion and subsequent 2 h reperfusion. SePost (n = 10) was given as sevoflurane 1.5-3% end-tidal concentration during reperfusion while controls (n = 12) were untreated. Aortic blood pressure was measured directly, while mixed-venous oxygen saturation and cardiac output were measured in the pulmonary artery. Cardiac work was determined as RPP. Post-mortem, histologic myocardial infarct size (IS), and area at risk were determined in transverse heart slices after tetrazolium stain., Results: Myocardial infarct size was reduced from (control) 55.0 (mean) ± 13.6% (standard deviation) to 32.5 ± 13.4% in group SePost (P = 0.0009). During reperfusion, SePost resulted in lower heart rate (P = 0.0003), cardiac output (P = 0.0123), mixed-venous oxygen saturation (P = 0.0103), blood pressure, and RPP (P < 0.0001). RPP was highly correlated to IS (P = 0.0055)., Conclusion: SePost (1.5-3%) reduced infarct size after regional myocardial ischemia in vivo and reduced cardiac work was significantly correlated to myocardial salvage., (© 2011 The Authors Acta Anaesthesiologica Scandinavica © 2011 The Acta Anaesthesiologica Scandinavica Foundation.)

Small rural hospitals in the United States have had challenging issues developing sustainable oncology programs. This is a report on the development of a successful rural oncology program. In 2006, the Tahoe Forest Health System in Truckee, CA, a remote mountain resort town, started a cancer program that was focused on addressing patient and family fears that are common to all cancer patients but more frightening in the rural setting. Four years later, it is a thriving program with significant community support, a creative academic affiliation, and a central focus of the future of the hospital. The Tahoe Forest Cancer Center developed a sustainable model for high quality cancer care that overcomes geographic, cultural and financial barriers. This structure may serve as a model for national rural health care.

Wear and delamination of conventional ultrahigh-molecular-weight polyethylene (UHMWPE) components used in total knee arthroplasty can compromise long-term performance. Radiation cross-linking and melt-annealing reduced wear and increased delamination resistance of UHMWPE. An alternative material is the alpha-tocopherol-stabilized irradiated UHMWPE (alphaTPE), with improved mechanical and fatigue properties vs irradiated and melted UHMWPE. We studied the wear and delamination resistance of alphaTPE and conventional UHMWPE (direct compression molded GUR 1050 and Himont 1900) under reciprocating unidirectional motion. Wear resistance was improved, and no delamination was observed in alphaTPE. Accelerated aging did not alter the wear and delamination behavior of alphaTPE. The GUR 1050 UHMWPE showed delamination and pitting when subjected to unidirectional reciprocating motion after accelerated aging. Himont 1900 UHMWPE showed no delamination when subjected to unidirectional reciprocating motion after accelerated aging. alpha-Tocopherol-stabilized irradiated UHMWPE is advanced for use in total knee arthroplasty due to its high resistance to wear, delamination, and oxidation., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: It has been shown that speckle tracking ultrasound (STU) is capable of measuring peak strain accurately in vitro over a range of compression rates and amplitudes. The aim of this study was to investigate the influence of different angles of insonation with a range of scanner settings., Methods: A tissue-mimicking phantom was cyclically deformed to imitate the beating heart. With different combinations of scanner settings, strain was measured by STU using sonomicrometry as reference., Results: Over a majority of parameter combinations, speckle tracking measured strain accurately. However, a combination of large echocardiographic image displacements, low frame rates, and small sector depths resulted in increased difference between STU and sonomicrometry. The angle of insonation and gain setting did not affect STU., Conclusion: Despite the limitations exhibited by image displacement, frame rate, and sector depth, STU remains a promising technique for angle-independent assessment of strain.

Background: Recent studies have demonstrated that inhalation anaesthetics, like sevoflurane, confer cardioprotection both experimentally and clinically. However, coexisting cardiac disease might diminish anaesthetic cardioprotection and could partly explain why the clinical results of cardioprotection with anaesthetics remain controversial--in contrast to solid experimental evidence. Concomitant left ventricular hypertrophy is found in some cardiac surgery patients and could change cardioprotection efficacy. Hypertrophy could potentially render the heart less susceptible to sevoflurane cardioprotection and more susceptible to ischaemic injury. We investigated whether hypertrophy blocks sevoflurane cardioprotection, and whether tolerance to ischaemia is altered by left ventricular hypertrophy, in an established experimental animal model of ischaemia-reperfusion., Methods: Anaesthetized juvenile pigs (n=7-12/group) were subjected to 45 min distal coronary artery balloon occlusion, followed by 120 min of reperfusion. Controls were given pentobarbital, while sevoflurane cardioprotection was achieved by 3.2% inhalation throughout the experiment. Chronic banding of the ascending aorta resulted in left ventricular hypertrophy development in two further groups and these animals underwent identical ischaemia-reperfusion protocols, with or without sevoflurane cardioprotection. Myocardial infarct sizes were compared post-mortem., Results: The mean myocardial infarct size (% of area-at-risk) was reduced from mean 55.0 (13.6%) (+/-SD) in controls to 17.5 (13.2%) by sevoflurane (P=0.001). Sevoflurane reduced the infarct size in hypertrophied hearts to 14.6 (10.4%) (P=0.001); however, in hypertrophic controls, infarcts were reduced to 34.2 (10.2%) (P=0.001)., Conclusion: Sevoflurane abrogated ischaemic injury to similar levels in both normal and left ventricular hypertrophied hearts.

For oral glucose tolerance test (OGTT) in mice, multiple blood samples need to be taken within a few hours from conscious mice. Today, a number of essential parameters may be analysed on very small amounts of plasma, thus reducing the number of animals to be used. It is, however, crucial to obtain high-quality plasma or serum in order to avoid increased data variation and thereby increased group sizes. The aim of this study was to find the most valid and reproducible method for withdrawal of blood samples when performing OGTT. Four methods, i.e. amputation of the tail tip, lateral tail incision, puncture of the tail tip and periorbital puncture, were selected for testing at 21 degrees C and 30 degrees C after a pilot study. For each method, four blood samples were drawn from C57BL/6 mice at 30 min intervals. The presence of clots was registered, haemolysis was monitored spectrophotometrically at 430 nm, and it was noted whether it was possible to achieve 30-50 microL blood. Furthermore, a small amount of extra blood was sampled before and after the four samplings for testing of whether the sampling induced a blood glucose change over the 90 min test period. All methods resulted in acceptable amounts of plasma. Clots were observed in a sparse number of samples with no significant differences between the methods. Periorbital puncture did not lead to any haemolysed samples at all, and lateral tail incision resulted in only a few haemolysed samples, while puncture or amputation of the tail tip induced haemolysis in a significant number of samples. All methods, except for puncture of the tail tip, influenced blood glucose. Periorbital puncture resulted in a dramatic increase in blood glucose of up to 3.5 mmol/L indicating that it is stressful. Although lateral tail incision also had some impact on blood glucose, it seems to be the method of choice for OGTT, as it is likely to produce a clot-free non-haemolysed sample, while periorbital sampling, although producing a high quality of sample, induces such a dramatic change in blood glucose that it should not be applied for OGTT in mice.

Our hypothesis was that cross-linked, ultrahigh-molecular weight polyethylene (UHMWPE) stabilized with vitamin E (alpha-tocopherol) would be wear-resistant and fatigue-resistant. Acetabular liners were radiation cross-linked, doped with vitamin E, and gamma-sterilized. Hip simulator wear rate of vitamin E-stabilized UHMWPE was approximately 1 and 6 mg/million-cycles in clean serum and in serum with third-body particles, respectively, a 4-fold to 10-fold decrease from that of conventional UHMWPE. The ultimate strength, yield strength, elongation at break, and fatigue resistance of vitamin E-stabilized UHMWPE were significantly higher than that of 100 kGy-irradiated and melted UHMWPE, and were unaffected by accelerated aging. Rim impingement testing with 3.7-mm-thick acetabular liners up to 2 million-cycles showed no significant damage of the cross-linked liners compared with conventional, gamma-sterilized in inert UHMWPE, vitamin E-stabilized liners. The data indicate good in vitro wear properties and improved mechanical and fatigue properties for vitamin E-stabilized, cross-linked UHMWPE.

Irradiation decreases the wear of ultra-high molecular weight polyethylene (UHMWPE) but generates residual free radicals, precursors to long-term oxidation. Melting or annealing is used in quenching free radicals. We hypothesized that irradiated and once-annealed UHMWPE would oxidize while irradiated and melted UHMWPE would not, and that the oxidation in the former would increase wear. Acetabular liners were real-time aged by immersion in an aqueous environment that closely mimicked the temperature and oxygen concentration of synovial fluid. After 95 weeks of real-time aging, once-annealed components were oxidized; the melted components were not. The wear rate of the real-time aged irradiated and once-annealed components was higher than the literature reported values of other contemporary highly cross-linked UHMWPEs. Single annealing after irradiation used with terminal gamma sterilization may adversely affect the long-term oxidative stability of UHMWPE components.

Standard therapy for AIDS associated NHL (AANHL) is toxic and often ineffective. Radioimmunotherapy (RIT) is an appealing alternative to chemotherapy because of the radiosensitivity of NHL and the ability of the Lym-1 monoclonal antibody to target therapeutic irradiation to NHL while relatively sparing normal tissue. A Phase I/II study of 90Y-2IT-BAD-Lym-1 was designed specifically for RIT of AANHL. The first patient has been treated with 15 mCi (7.5 mCi/m2) of 90Y-2IT-BAD-Lym-1, after an imaging dose of 111In-2IT-BAD-Lym-1. Before RIT, AANHL in the maxillary sinus extended into the oral cavity and axillary adenopathy was present. Imaging showed excellent accumulation of 111In-2IT-BAD-Lym-1 in the tumors. Substantial shrinkage of the oral lymphoma was observed 18 hours after the therapy dose of 90Y-2IT-BAD-Lym-1 and axillary adenopathy had disappeared by one week after RIT. Transient Grade IV myelosuppression was the only notable toxicity. Further RIT cycles were precluded by development of an antibody response (HAMA) against Lym-1. This novel preliminary study has shown that Lym-1 can target AANHL and produce significant tumor regression thereby providing encouragement to proceed with additional patients.