To investigate student clinical placement concerns and opinions, during the initial COVID-19 pandemic outbreak and to inform educational institution support planning.
Between mid-June to mid-July ...2020, educational institutions from 12 countries were invited to participate in an online survey designed to gain student radiographer opinion from a wide geographical spread and countries with varying levels of COVID-19 cases.
1277 respondents participated, of these 592 had completed clinical placements during January to June 2020. Accommodation and cohabiting risks were identified as challenging, as was isolation from family, travel to clinical placements, and to a lesser extent childcare. Students stated they had been affected by the feeling of isolation and concerns about the virus whilst on placement. Overall 35.4% of all respondents were ‘Not at all worried’ about being a radiographer, however, 64.6% expressed varying levels of concern and individual domestic or health situations significantly impacted responses (p ≤ 0.05). Year 4 students and recent graduates were significantly more likely to be ‘Not worried at all’ compared to Year 2 and 3 students (p ≤ 0.05). The need for improved communication regarding clinical placements scheduling was identified as almost 50% of students on clinical placements between January to June 2020 identified the completion of assessments as challenging. Furthermore, only 66% of respondents with COVID-19 imaging experience stated being confident with personal protective equipment (PPE) use.
Student radiographers identified key challenges which require consideration to ensure appropriate measures are in place to support their ongoing needs. Importantly PPE training is required before placement regardless of prior COVID-19 imaging experience.
As the next academic year commences, the study findings identify important matters to be considered by education institutions with responsibility for Radiography training and as students commence clinical placements during the on-going global COVID-19 pandemic.
Summary
This study describes a radiographic survey of the anatomical development of the distal extremity of the manus in the donkey from 0 to 2 years of age. The right distal limb of 10 donkey foals, ...born in the spring of 2012, underwent radiographs every month for the first 6 months of age and every 3 months during the following 18 months. Latero‐medial radiographs with and without barium marker at the coronary band and dorso‐palmar radiographs with both front feet in weight bearing were obtained. The distal physis of the third metacarpal bone and the proximal physis of the proximal phalanx (phalanx proximalis) were closed at the mean age of 18.6 months. The distal physis of the proximal phalanx appeared as a clear radiolucent line at 2 weeks of age and was still subtly visible in some donkeys at 24 months. The proximal physis of the middle phalanx (phalanx media) was closed at the mean age of 16.7 months. The distal physis of this phalanx was visible at birth, but closed at 4 days. The distal phalanx (phalanx distalis) was triangular at birth. At the age of 20–21 months, the palmar processes (processus palmares) were both developed. The navicular bone (os sesamoideum distalis) was developed at the mean age of 9 months. The proximal sesamoid bones (ossa sesamoidea proximalia) were seen in continuously development during the 24 months. It seems that the physes in the distal extremity of the manus in the donkey close at an older age than the physes in the horse.
Summary This study describes a radiographic survey of the anatomical development of the distal extremity of the manus in the donkey from 0 to 2 years of age. The right distal limb of 10 donkey foals, ...born in the spring of 2012, underwent radiographs every month for the first 6 months of age and every 3 months during the following 18 months. Latero-medial radiographs with and without barium marker at the coronary band and dorso-palmar radiographs with both front feet in weight bearing were obtained. The distal physis of the third metacarpal bone and the proximal physis of the proximal phalanx (phalanx proximalis) were closed at the mean age of 18.6 months. The distal physis of the proximal phalanx appeared as a clear radiolucent line at 2 weeks of age and was still subtly visible in some donkeys at 24 months. The proximal physis of the middle phalanx (phalanx media) was closed at the mean age of 16.7 months. The distal physis of this phalanx was visible at birth, but closed at 4 days. The distal phalanx (phalanx distalis) was triangular at birth. At the age of 20-21 months, the palmar processes (processus palmares) were both developed. The navicular bone (os sesamoideum distalis) was developed at the mean age of 9 months. The proximal sesamoid bones (ossa sesamoidea proximalia) were seen in continuously development during the 24 months. It seems that the physes in the distal extremity of the manus in the donkey close at an older age than the physes in the horse.
University "spin-off" companies are high technology ventures that originate from research work in a university, resulting in the generation of intellectual property and, usually, the subsequent ...involvement of key researchers. The analysis distinguishes between 14 new technology-based firms that are university "spin-off" companies and 14 community companies that had no connection with a university. The analysis described in this paper is based on a specially developed assessment methodology that comprises a structured decision-making model. This technology assessment methodology is based on the identification of key criteria for analysis. The study identified the most significant variable for university "spin-off" companies being that of protecting competitive advantage. This result can be attributed to the need for universities to protect their intellectual property, which is to be rewarded with an equity stake in the company. Two other significant variables were identified as the level of product innovation (compared to competitors) and market criteria (including the potential customer base). PUBLICATION ABSTRACT
Ketoconazole inhibits testosterone biosynthesis in men, but the exact site of its action on the androgen pathway remains to be established. To examine this question, we measured several steroids in ...the androgen and glucocorticoid pathways in normal men before and after receiving either a single dose of 200 mg ketoconazole or placebo in a cross-over randomized trial. Total and free plasma testosterone fell to levels 60% below basal within 4-8 h (P less than 0.02 in all) and then returned to control concentrations by 24 h after drug administration. The transient alterations of plasma testosterone correlated well with ketoconazole blood levels, which peaked at 2 h and fell exponentially thereafter. A compensatory increase in plasma LH at 24 h in the drug but not placebo group was consistent with the decrease in plasma testosterone. The levels of plasma androstenedione paralleled those of testosterone in the ketoconazole-treated subjects. In marked contrast, plasma 17 alpha-hydroxyprogesterone increased at 4-8 h (all P less than 0.02) before returning to basal values at 24 h. This rise in precursor with fall in product steroid implicated an effect of ketoconazole on the C17-20 lyase enzyme. This conclusion was supported by the highly significant increase in the ratio of plasma 17 alpha-hydroxyprogesterone to androstenedione observed between 2 and 24 h after drug administration. The effect of ketoconazole at this dose level appeared relatively specific, since no decrements in plasma cortisol or 11-desoxycortisol were found. During chronic administration of 200 mg ketoconazole daily, decrements of plasma testosterone 2-4 h after drug administration were minimal and documented only by paired comparisons within subjects but not by unpaired tests between normal men and men receiving drug. The lack of major effects on testosterone levels long term at this dosage probably explain why few androgen-related side effects with this drug were previously reported. Ketoconazole, therefore, represents another compound with relatively selective effects on a cytochrome P-450-mediated steroid hydroxylation step, namely that involved with C17-20 lyase.
Aromatization of androgens into estrogens may explain some of the skeletal action of androgens. We examined the effect of the aromatase inhibitor Vorozole (VOR) on skeletal growth and mineral ...accumulation in growing 6-week-old male Wistar rats. Rats were either Sham-operated (Sham) or Orchidectomized (Orch) and treated with or without the aromatase inhibitor VOR. One Sham-operated group was killed at Baseline (Base); the four other groups (Sham, Sham + VOR, Orch, Orch + VOR) were killed 18 weeks after surgery. As expected, all groups gained body weight, but body weight gain was significantly (-25%) lower in Orch, Orch + VOR, and Sham + VOR. Both bone formation, as assessed by serum osteocalcin, and bone resorption, as assessed by urinary (deoxy)pyridinoline, decreased significantly in all groups compared with Base. Orchidectomy resulted in a relative increase of biochemical markers of bone formation and resorption compared with Sham. Treatment with VOR, however, resulted only in a very moderate increase of (deoxy)pyridinoline compared with Sham. As expected, femoral length increased compared with Base, but orchidectomy reduced the relative growth of the femur whereas VOR did not influence femoral length. Ex vivo, densitometric and geometric properties of the femora were evaluated by peripheral computerized quantitative tomography (pQCT) and dual-energy x-ray absorptiometry (DXA). The lumbar vertebrae were measured by DXA. At the end of the experimental period, volumetric trabecular bone mineral density (vTBMD) measured at the distal end of the femur was significantly lower not only in both Orch groups but also in Sham + VOR. The decrease of cancellous bone density in Sham + VOR was lower than in the orchidectomized animals. A relative decrease of femoral inner and outer diameters compared with Sham and Base was observed in both Orch groups and in Sham + VOR, suggesting that both orchidectomy and VOR-treatment inhibited periosteal bone formation and endosteal bone resorption. Only orchidectomy, however, resulted in a decrease of cortical thickness. Bone area, mineral content, and density of both femora and lumbar vertebrae, measured by DXA, were decreased to a similar extent by VOR and Orch (bone mineral content of the femur was 467 +/- 18 mg in Orch and 461 +/- 10 mg in Sham +/- VOR vs. 521 +/- 11 mg in Sham; P < 0.001). In conclusion, treatment with the aromatase inhibitor VOR impairs body weight gain and skeletal modeling and decreases bone mineral density. Aromatase inhibition had similar final effects on bone mass and size as castration, but with less marked effects on bone turnover.
Background Defining the complication rate of endoscopy performed across an entire city will capture usual as opposed to referral center data. Objective Our purpose was to evaluate the current ...practice of colonoscopy and complications associated with lower GI endoscopy in usual clinical practice. Design All admissions within 30 days of an outpatient lower GI endoscopy at any of the 6 adult-care Winnipeg hospitals were identified. This includes endoscopy for both complex and routine patients. A chart audit of all cases with potential complications was performed. Results A total of 24,509 outpatient lower GI endoscopies for adults were performed at the 6 hospitals over the 2 study years (April 1, 2004, to March 31, 2006). There were 303 admissions with potential complications. The colonoscopy completion rate was 65% (72% for gastroenterologists vs 59% for general surgeons, P < .005). Quality of bowel preparation and nature of polyps were often not documented. The overall rate of complications was 2.9/1000 procedures; the perforation rate after polypectomy was 1.8/1000; and the postpolypectomy bleeding rate was 6.4/1000. Most (67%) complications were recognized after discharge for the index procedure. The complication rate was highest for the endoscopists performing fewer than 200 procedures per year (5.4/1000 vs 2.7/1000 for the rest, P = .02, relative risk 2 95% CI, 1.1-3.7). Limitations Chart audit was limited to cases requiring admission within 30 days of the index procedure. Conclusions The overall complication rate after lower GI endoscopy in usual clinical practice in Winnipeg is comparable to that previously reported. A higher complication rate after endoscopy by low-volume endoscopists needs to be further evaluated. The reporting of endoscopy must be standardized to enhance outcomes interpretation.
The pharmacokinetics of a novel antipsychotic agent, risperidone, and the prolactin response were studied in 12 dextromethorphan‐phenotyped healthy men after administration of 1 mg risperidone ...intravenously, intramuscularly, and orally. The formation of the equipotent major metabolite, 9‐hydroxyrisperidone, exhibited CYP2D6‐related polymorphism. The plasma area under the concentration—time curve from time zero to infinity ratio of 9‐hydroxyrisperidone to risperidone averaged 3 (intravenous and intramuscular) and 6 (oral administration) in the extensive metabolizers and 0.2 in the poor metabolizers. Risperidone half‐life was about 3 hours in extensive metabolizers and 22 hours in poor metabolizers. Risperidone absolute oral bioavailability was 66%. The pharmacokinetics of the active moiety (risperidone plus 9‐hydroxyrisperidone) varied little among subjects (mean terminal half‐life, 20 ± 21/2 hours; absolute oral and intramuscular bioavailability, 100%). The prolactin response correlated best with the plasma active moiety, which showed little hysteresis. It is concluded that risperidone metabolic polymorphism on increased plasma prolactin is minimal and that the active moiety is clinically relevant.
Clinical Pharmacology and Therapeutics (1993) 54, 257–268; doi:10.1038/clpt.1993.146
P450-dependent enzymes as targets for prostate cancer therapy De Coster, R.; Wouters, W.; Bruynseels, J.
Journal of steroid biochemistry and molecular biology,
1996, 1996-Jan, 1996-1-00, Letnik:
56, Številka:
1
Journal Article, Conference Proceeding
Recenzirano
Metastatic prostate adenocarcinoma is a leading cause of cancer-related deaths among men. First line treatment is primarily aimed at blocking the synthesis and action of androgens. As primary ...endocrine treatment, androgen deprivation is usually achieved by orchidectomy or LHRH analogues, frequently combined with androgen receptor antagonists in order to block the residual adrenal androgens. However, nearly all the patients will eventually relapse. Available or potential second line therapies include, among others, alternative endocrine manipulations and chemotherapy.
Cytochrome
P450-dependent enzymes are involved in the synthesis and/or degradation of many endogenous compounds, such as steroids and retinoic acid. Some of these enzymes represent suitable targets for the treatment of prostate cancer.
In first line therapy, inhibitors of the
P450-dependent 17,20-lyase may achieve a maximal androgen ablation with a single drug treatment. Ketoconazole at high dose blocks both testicular and adrenal androgen biosynthesis but its side-effects, mainly gastric discomfort, limit its widespread use. A series of newly synthesized, more selective, steroidal 17,20-lyase inhibitors related to 17-(3-pyridyl)androsta-5,16-dien-3β-ol, may open new perspectives in this field.
In prostate cancer patients who relapse after surgical or medical castration, therapies aiming at suppressing the remaining adrenal androgen biosynthesis (ketoconazole) or producing a medical adrenalectomy (aminoglutethimide + hydrocortisone) have been used, but are becoming obsolete with the generalization of maximal androgen blockade in first line treatment. The role of inhibition of aromatase in prostate cancer therapy, which was postulated for aminoglutethimide, could not be confirmed by the use of more selective aromatase inhibitors, such as formestane.
An alternative approach is represented by liarozole fumarate (LIA), a compound that blocks the
P450-dependent catabolism of retinoic acid (RA).
In vitro, it enhances the antiproliferative and differentiation effects of RA in cell lines that express RA metabolism, such as F9 teratocarcinoma and MCF-7 breast carcinoma cells.
In vivo, monotherapy with LIA increases RA plasma levels and, to a greater extent, endogenous tissue RA levels leading to retinoid-mimetic effects. In the rat Dunning prostate cancer models, it inhibits the growth of androgen-independent as well as androgen-dependent carcinomas relapsing after castration. Concurrently, changes in the pattern of cytokeratins characteristic of increased differentiation were observed. Early clinical trials show that LIA, in second or third line therapy in metastatic prostate cancer, induces PSA responses in about 30% of unselected patients. In some patients regression of soft tissue metastasis has been observed. In a subgroup of patients, an important relief of metastatic bone pain was also noted.
A nonsteroidal aromatase inhibitor vorozole (VOR) was administered to aged (12 months old) male Wistar rats and its effect was compared with the effect of androgen deficiency. The rats were either ...sham-operated (SHAM) or orchidectomized (ORCH) and treated with or without VOR. Thus, four experimental groups were created (SHAM, ORCH, SHAM + VOR, ORCH + VOR). The follow-up period was 4 months. At the end of the experimental period, bone mineral density (BMD) of the first four lumbar vertebrae and right femur was measured ex vivo with dual-energy X-ray absorptiometry, bone formation was evaluated by serum osteocalcin, and bone resorption by urinary excretion of (deoxy)pyridinoline. Orchidectomy increased bone resorption 2- to 3-fold whereas bone formation was only slightly increased. Treatment of intact male rats with VOR also increased bone resorption (+30% increase) whereas bone formation was not increased in this SHAM + VOR group. Their BMD was 7% lower in the femur (P < 0.01) and 6% lower in the lumbar vertebrae (P < 0.01) compared with the SHAM group that had not received VOR. Moreover, this decrease of bone mineral density was not significantly different from the expected decrease of bone density observed in the ORCH groups (6-10%). This was also reflected by a decrease of calcium content of the first four lumbar vertebrae of 15% (P < 0.001) in the SHAM + VOR group and 9-14% (P < 0.05) in the ORCH groups compared with the SHAM group, respectively. These data therefore suggest that inhibition of aromatization of androgens into estrogens increases bone resorption and bone loss similar to that observed after complete removal of androgens. Aromatization of androgens into estrogens may therefore, at least partly, explain the effects of androgens on skeletal maintenance.
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