Developing an Educational Framework for Urological Nursing: Using a World Café approach to gain an emerging international understanding of issues,challenges and responses

A series of three World Café events centred on the topic of developing an Educational Framework for Urological Nursing [EFUN] were held by the British Association of Urological Nurses [BAUN], the European Association of Urology Nurses [EAUN] and the Australian and New Zealand Urological Nursing Society [ANZUNS] between 2017 and 2019. About 376 urology nurses participated in these “conversations that matter” and generated 1047 individual response items that were grouped into themes to assist the three associations to take the creation of an EFUN to the next level. Areas explored centred on four aspects: what any agreed educational framework for urology nursing should contain; the academic level at which education should be provided; who should be recruited as collaborators on writing an educational framework and, lastly, just how any emergent framework should be used. Analysis of the conversational data indicate that there exists within the urological nursing community a collective wisdom regarding their educational needs and how these needs should be met.     

Mildly decreased preoperative bilirubin levels are associated with infections after shoulder and knee arthroplasty

Increasing numbers of arthroplasties are also accompanied by postoperative infections. The main purpose was to evaluate preoperative serum bilirubin levels between patients with and without infections after shoulder and knee arthroplasties. For this retrospective case-control single-center study, a total of 108 patients were extracted from a prospectively collected database. Eighteen patients with infections after shoulder (n = 8) and knee (n = 10) arthroplasty were matched by age, gender, and implant type in a 1:5-scenario to 90 patients (40 shoulders and 50 knees) without postoperative infection. Demographic data, preoperative blood parameters, and postoperative infection-related outcomes were evaluated. Total bilirubin was the only preoperative parameter significantly different between the infection (8.21 ± 3.25 μmol/L or 0.48 ± 0.19 mg/dL) and noninfection (10.78 ± 4.62 μmol/L or 0.63 ± 0.27 mg/dL; P = .014) group, while C-reactive protein and other liver parameters were similar between the groups. Significantly more controls (92.1%) had preoperative bilirubin levels above 8.72 μmol/L or 0.51 mg/dL than cases (7.9%; P = .007). The 5-year infection survival-rate was 65.6% for patients with preoperative bilirubin levels < 8.72 μmol/L or < 0.51 mg/dL and 91.2% with ≥ 8.72 μmol/L or ≥ 0.51 mg/dL. Mildly decreased preoperative bilirubin levels with a cutoff at 8.72 μmol/L or 0.51 mg/dL were significantly associated to patients with infections after shoulder and knee arthroplasty. There were no differences in other blood parameters or comorbidities between patients with infections and their matched-controls.     

Novel phenotype of mouse spermatozoa following deletion of nine β-defensin genes

β-defensin peptides are a large family of antimicrobial peptides. Although they kill microbes in vitro and interact with immune cells, the precise role of these genes in vivo remains uncertain. Despite their inducible presence at mucosal surfaces, their main site of expression is the epididymis. Recent evidence suggests that a major function of these peptides is in sperm maturation. In addition to previous work suggesting this, work at the MRC Human Genetics Unit, Edinburgh, has shown that homozygous deletion of a cluster of nine β-defensin genes in the mouse results in profound male sterility. The spermatozoa derived from the mutants had reduced motility and increased fragility. Epididymal spermatozoa isolated from the cauda region of the homozygous mutants demonstrated precocious capacitation and increased spontaneous acrosome reactions compared with those from wild-types. Despite this, these mutant spermatozoa had reduced ability to bind to the zona pellucida of oocytes. Ultrastructural examination revealed a disintegration of the microtubule structure of mutant-derived spermatozoa isolated from the epididymal cauda region, but not from the caput. Consistent with premature acrosome reaction and hyperactivation, spermatozoa from mutant animals had significantly increased intracellular calcium content. This work demonstrates that in vivo β-defensins are essential for successful sperm maturation, and that their disruption alters intracellular calcium levels, which most likely leads to premature activation and spontaneous acrosome reactions that result in hyperactivation and loss of microtubule structure of the axoneme. Determining which of the nine genes are responsible for the phenotype and the relevance to human sperm function is important for future work on male infertility.     

Sonographic features of benign thyroid nodules: interobserver reliability and overlap with malignancy.

OBJECTIVE: To prospectively determine the sonographic findings of nodular hyperplasia of the thyroid, to compare these with reported findings associated with malignancy, and to assess interobserver reliability. METHODS: Seventy thyroid nodules were scanned, and then biopsies of the nodules were performed under sonographic guidance with fine-needle cytologic analysis; in all cases images were reviewed by 2 experienced radiologists without knowledge of clinical outcome. Findings reported associated with malignancy were specifically assessed. Interobserver agreement between the expert and secondary readers for each finding was calculated by the kappa or weighted kappa statistic and the Fisher exact test of independence. RESULTS: There were 68 benign and 2 malignant nodules in a population of 63 female and 7 male patients. The mean benign nodule size was 2.9 cm; 60% were solid; 54% were hypoechoic; 59% were microlobulated or macrolobulated; 47% had central vascularity; 24% contained calcifications; and 82% were elliptical in shape. There was very good interobserver reliability for the presence of calcium (kappa = 0.91) and good agreement for the presence and location of vascularity (kappa = 0.75) and the amount of cystic components (kappa = 0.62; all P < .01). CONCLUSIONS: Sixty-nine percent of benign nodules had at least 1 finding reported previously as associated with malignancy. The interobserver reliability of the sonographic findings was good to very good for 3 of the 5 findings assessed.     

Thermodynamic stability of wild-type and mutant p53 core domain

Some 50% of human cancers are associated with mutations in the core domain of the tumor suppressor p53. Many mutations are thought just to destabilize the protein. To assess this and the possibility of rescue, we have set up a system to analyze the stability of the core domain and its mutants. The use of differential scanning calorimetry or spectroscopy to measure its melting temperature leads to irreversible denaturation and aggregation and so is useful as only a qualitative guide to stability. There are excellent two-state denaturation curves on the addition of urea that may be analyzed quantitatively. One Zn²⁺ ion remains tightly bound in the holo-form of p53 throughout the denaturation curve. The stability of wild type is 6.0 kcal (1 kcal = 4.18 kJ)/mol at 25°C and 9.8 kcal/mol at 10°C. The oncogenic mutants R175H, C242S, R248Q, R249S, and R273H are destabilized by 3.0, 2.9, 1.9, 1.9, and 0.4 kcal/mol, respectively. Under certain denaturing conditions, the wild-type domain forms an aggregate that is relatively highly fluorescent at 340 nm on excitation at 280 nm. The destabilized mutants give this fluorescence under milder denaturation conditions.     

Transplacental IgG Subclass Concentrations in Pregnancies at Risk of Haemolytic Disease of the Newborn

The relationship of haemolytic disease of the newborn (HDN) to the transplacental passage of the four IgG subclasses was assessed at varous gestational ages by comparing the maternal and fetal IgG subclass concentrations in 34 pregnancies at risk of HDN with those in 30 pregnancies not at risk. Higher maternal and fetal IgG1 levels were attained in pregnancies at risk of HDN than in pregnancies not at risk. In contrast, a slight decrease in maternal IgG2 and IgG4 levels occurred in pregnancies at risk of HDN, as compared with a slight rise in maternal IgG2 and IgG4 levels in pregnancies not at risk of HDN. Changes in fetal IgG2 and 4 concentrations in either type of pregnancy were very similar, showing only slight increases between the 19th and 34th week of gestation. A slight decrease in maternal IgG3 occurred in both types of pregnancy. In contrast, higher and fairly steady levels of fetal IgG3 were observed in fetuses not at risk of HDN throughout gestation, when compared with those in 'at risk' pregnancies. However, the statistical reliability of these results is not clear since only small numbers of samples were tested and because wide variations in IgG concentrations were observed. The IgG subclass concentrations in 50 paired maternal and cord blood samples were also measured and revealed that IgG1 levels were substantially higher in cord rather than maternal blood; cord and maternal IgG2, 3 and 4 levels, on the other hand, were fairly similar.     

Insights into Mechanisms of Cisplatin Resistance and Potential for Its Clinical Reversal

Cisplatin in combination with other cytotoxic agents is the backbone for a potential cure of testicular germ cell neoplasms and is a critical factor in the substantial activity observed in the treatment of small cell lung cancer, bladder cancer, and ovarian germ cell tumors. Resistance to cisplatin at the onset of treatment or at relapse limits its curative potential, however. Laboratory studies using both cells selected for cisplatin resistance by exposure to sublethal concentrations and biopsy specimens from patients' tumors provide insights for the potential mechanisms of resistance. The mechanisms identified in vitro include a complex and wide array of related and unrelated pathways such as alterations in cellular drug transport, enhanced DNA repair dependent and independent of signal transduction pathways, and enhanced intracellular detoxification such as glutathione and metallothionein systems. Studies of these mechanisms have identified a number of agents with known potential for administration to humans and that reverse cisplatin resistance in vitro; for example, reversal of cellular accumulation defects by dipyridamole; inhibition of DNA repair by hydroxyurea, pentoxifylline, and novobiocin; inhibition of the glutathione system by ethacrynic acid and buthionine sulfoximine; and inhibition of signal transduction pathways by cyclosporine, tamoxifen, and calcium channel-blocking agents. Current phase I clinical trials are focusing on the most effective doses and schedules to administer these agents in combination with cisplatin. Initial uncontrolled trials in limited numbers of patients suggest that the addition of modulators of cisplatin has the potential to reverse resistance in patients previously failing therapy. Another promising avenue for circumventing cisplatin resistance is the development of noncross-resistant platinum analogs.     

Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies

Summary Cytosine arabinsodie (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m² as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9–12 and 21–24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m²×2 doses of ara-C and 50 mg/m² of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.Supported in part by grants from the National Cancer Institute (CA-12197 and CA-09422) and the American Cancer Society CF-85-182     

Striatal D(2) receptor occupancy in bipolar patients treated with olanzapine.

We explored the relationship between striatal dopamine-2 (D(2)) receptor occupancy and extra-pyramidal symptoms (EPS) in bipolar patients receiving olanzapine. Seventeen patients with a DSM-IV diagnosis of bipolar disorder were treated with 5-45 mg/day olanzapine for at least 14 days. After that period, D(2) receptor occupancy was determined using Iodobenzamide (IBZM) and SPECT. EPS were assessed by the Simpson-Angus Scale (SAS) and Barnes-Akathisia Scale (BAS). We found a dose-dependent increase in occupancy: 5 mg led to 28-50%, 10 mg to 40-68%, 15 mg to 69%, 20 mg to 57-66%, 30 mg to 66% and 45 mg to 80% D(2) receptor occupancy; and a significant correlation between plasma levels and occupancy (R(2)=.55, P=.001). Similar to schizophrenic patients, bipolar patients did not exhibit EPS at D(2) occupancy levels of 28 to 80%. Although we did not find an increased vulnerability for acute EPS in bipolar patients receiving olanzapine at clinical relevant doses, this needs to be replicated with larger sample sizes.