The impact of a structured clinical training course on interns' self-reported confidence with core clinical urology skills.

BACKGROUND: Undergraduate training in core urology skills is lacking in many Irish training programmes. AIMS: Our aim was to assess newly qualified doctors' experience and confidence with core urological competencies. METHODS: A questionnaire survey covering exposure to urology and confidence with core clinical skills was circulated to all candidates. The group then attended a skills course covering male/female catheterisation, insertion of three-way catheters, bladder irrigation and management of long-term suprapubic catheters. The groups were re-surveyed following the course. RESULTS: Forty-five interns completed the pre-course questionnaire (group 1) and 27 interns completed the post-course questionnaire (group 2). 24/45 (53%) had no experience of catheter insertion on a patient during their undergraduate training. 26/45 (58%) were unsupervised during their first catheter insertion. 12/45 (27%) had inserted a female catheter. 18/45 (40%) had inserted a three-way catheter. 12/45 (27%) had changed a suprapubic catheter. 40/45 (89%) in group 1 reported 'good' or 'excellent' confidence with male urinary catheterisation, compared to 25/27 (92.5%) in group 2. 18/45 (40%) in group 1 reported 'none' or 'poor' confidence with female catheterisation, compared to 7/27 (26%) in group 2. 22/45 (49%) in group 1 reported 'none' or 'poor' confidence with insertion of three-way catheters, compared to 2/27 (7%) in group 2. 32/45 (71%) in group 1 reported 'none' or 'poor' confidence in changing long-term suprapubic catheters, falling to 3/27 (11%) in group 2. CONCLUSION: This study raises concerns about newly qualified doctors' practical experience in urology. We suggest that this course improves knowledge and confidence with practical urology skills and should be incorporated into intern induction.

Avoidable iatrogenic complications of male urethral catheterisation and inadequate intern training: a 4-year follow-up post implementation of an intern training programme.

OBJECTIVE: To assess the impact of a structured training programme in urethral catheterisation (UC) targeted at newly qualified junior doctors on rates of iatrogenic catheter morbidity within a tertiary care referral centre. SUBJECTS AND METHODS: Male UC-related morbidities were retrospectively identified from our computerised inpatient urology consultation system over a 1-year period from July 2010 to June 2011. Relevant medical records were also reviewed. Results were compared with an initial study performed between July 2006 and June 2007, prior the introduction of a structured training programme in our institution. An anonymous questionnaire was used for the subjective assessment of interns about confidence in catheterising post introduction of the programme. RESULTS: Of 725 urological consultations, 29 (4%) were related to complications arising from male UC during the 1 year period. This reflected a statistically significant decrease when compared to our 2007 figures, 51/864 (6%) (p < 0.05). Again, the most common indication for UC was monitoring urinary output for acute medical illness (19/29, 66%). The most common complication was urethral trauma (16/29, 55%). Of the 29 cases of UC-related morbidity, 18 (62%) resulted from interns performing UC, a decrease of 12% from our original paper. A drop of 27% was seen in the rates of UC related morbidity attributable to interns during the first 6 months of internship (July-December). Overall, 70% (vs 40% original study) of interns felt that their practical training was adequate since introduction of the programme (p < 0.01) with 53% considering theoretical training adequate (vs 16% original study (p < 0.01). When asked were they confident in performing UC, 63% said they were compared to 35% before introduction of the programme (p < 0.05). CONCLUSIONS: UC-related iatrogenic morbidity is not uncommon even in a tertiary-care teaching hospital. Implementation of a structured training programme in UC prior to the commencement of intern year has been shown to result in a significant decrease in the amount of iatrogenic UC related morbidity.

Autotransplantation of a single functioning kidney following rupture of renal artery aneurysm.

Renal artery aneurysms (RAA) are the second most common visceral artery aneurysm. In cases of rupture they pose a significant and emergent surgical challenge. Extracorporeal arterial reconstruction and autotransplantation is often necessary in certain complex cases that are not amenable to aneurysm repair in vivo. We report a case of a 35 year old female with a RAA in a solitary functioning kidney, requiring ex vivo reconstruction and autotransplantation to the iliac vessels.

A rare case of recurrent urachal adenocarcinoma of the bladder.

Urachal carcinoma is a rare, aggressive malignancy accounting for less than 1% of bladder neoplasms. These tumours are usually adenocarcinomas and occur at the dome or anterior wall of the bladder. They often escape early clinical detection, growing for prolonged periods prior to diagnosis, resulting in local invasion and systemic spread before therapeutic intervention is initiated. We present the case of a recurrent urachal carcinoma in a young female.

A review of inpatient urology consultations in an Irish tertiary referral centre.

INTRODUCTION: Our institution is a 680-bed tertiary referral centre with broad medical and surgical subspecialty services. We retrospectively audited the pattern of inpatient consultations from all specialities within our institution to the urology department over a 1-year period. METHODS: All consultations to the urology service were identified from our computerised inpatient consultation system from July 2010 to June 2011. Follow up data on investigations, interventions and subsequent outpatient appointments were also identified by review of individual patient discharge letters. RESULTS: Seven hundred and twenty five inpatient consultations were received over the period. The male to female ratio was 7:3. Mean age of patients was 66 (15-96) years. Seventy three percent of referrals were from medical sub-specialities, most commonly nephrology (17%), gastroenterology (11%) and respiratory medicine (9%). The remainder were from general surgery (16%) and other surgical sub specialities (11%). Interns (66%) and senior house officers (SHO) (28%) communicated the majority of consults. Male lower urinary tract/benign prostate related issues resulted in 25% of all consultations. Less than half of consults (47%) resulted in interventions initiated by urology, most commonly of which were catheter insertions (48%) and endoscopic procedures (35%). Only 43% of consultations were followed up in the outpatients setting. CONCLUSIONS: Inpatient consultations constitute a significant workload for urology services. The majority of these referrals did not require any urological intervention and could have been seen routinely in the outpatient setting. Providing structured referral guidelines and achieving better communication with referring teams may help to optimise this service.

Tetramethylpiperidine-substituted phenazines inhibit the proliferation of intrinsically multidrug resistant carcinoma cell lines.

The effects of nine new tetramethylpiperidine (TMP)-substituted phenazines on the growth of a human esophageal cancer cell line (WHCO3), two human hepatocellular carcinoma cell lines (PLC and HepG2) and three human colon cancer cell lines (CaCo2, COLO 320DM and HT29) were compared to those of clofazimine, B669 and five standard chemotherapeutic agents. The three most active TMP-substituted phenazines against these cell lines were B3962, B4126 and B4125 with mean IC50 values for all the cancer cell lines tested of 0.36, 0.47 and 0.48 microg/ml respectively. B3962 and B4126, but not B4125 were also the most active against a semi-continuous human fibroblast culture (MRC5). The compound with the highest tumor specificity relative to the fibroblast culture, was B4125. Importantly, there was minimal variation in sensitivity of the different cell lines, including a multidrug resistant cell line (COLO 320DM) expressing high levels of P-glycoprotein, to the TMP-substituted phenazines. This was not the case with the standard chemotherapeutic agents. The efficacy of compounds such as B4125 against a broad spectrum of multidrug resistant cancer cell lines, together with their relatively high tumor specificity, suggests that these agents may be useful in the treatment of intrinsically resistant cancers such as colon and liver cancer.

Transferring dying nursing home residents to the hospital: DON perspectives on the nurse's role in transfer decisions.

This qualitative study elicits factors that influence decision-making by nurses about transferring a dying resident from the nursing home to the hospital. Focus groups with directors of nursing (DONs) from long-term care facilities revealed those decisions are influenced by knowledge (or lack thereof) of resident or family preferences, nurse interactions with physicians, nursing home technological and personnel resources, and nurse concerns about institutional liability. DONs can improve transfer decisions by communicating with all parties, clarifying nursing home processes for end-of-life care, and scheduling early and thorough conversations with residents and families about end-of-life care. DONs can implement improvements through staff education on communication issues, rigorous evaluation and performance outcome measures related to patient transfer, and conveyance to staff of the institution's mission and the nursing service's values.

The history of obstetrics in Northern Ireland 1921-1992.

In 1921 there was little provision for the care of the pregnant woman in Northern Ireland where there were only two hospitals staffed by specialist obstetricians. The mortality statistics reflected this, the province having the highest maternal mortality and the second highest infant mortality rates in the United Kingdom. There was little progress until the establishment of the National Health Service in 1948. Within a short time, excellent hospital specialist and domiciliary midwifery services were developed. Scientific advances, mainly during the 1970's, led to further expansion of the specialist service and the disappearance of the general practitioner service. These advances have again been reflected in the statistics. The maternal mortality is now zero and the perinatal mortality 8 per 1,000 births.

Tetramethylpiperidine-substitution increases the antitumor activity of the riminophenazines for an acquired multidrug-resistant cell line.

The multidrug resistance (MDR)-neutralizing and cytotoxic properties of five tetramethylpiperidine (TMP)-substituted phenazines were compared with those of their corresponding isopropyl-substituted analogues using a P-glycoprotein (P-gp)-expressing small cell lung cancer cell line (H69/LX4). All of the TMP-substituted phenazines tested outperformed their isopropyl analogues with respect to both cytotoxic and chemosensitizing properties, indicating the importance of TMP-substitution when designing novel riminophenazines with increased activity against MDR cancer cell lines. Of the TMP-substituted phenazines tested, B4112, chlorinated at position 3 of the phenyl- and anilino-rings, had the most potent anti-cancer activity in vitro, making this agent a potential candidate for evaluation in experimental and clinical oncology.

Clofazimine and B4121 sensitize an intrinsically resistant human colon cancer cell line to P-glycoprotein substrates.

The potential of B4121 to sensitize three intrinsically resistant human colon cancer cell lines (CaCo2, ATCC HTB 37; COLO 32 DM, ATCC CCL 220; HT-29, ATCC HTB 38) to vinblastine, doxorubicin, daunorubicin, paclitaxel, taxotere and cisplatin at a non-toxic, therapeutically relevant concentration of 0.25 microg/ml was compared with that of clofazimine at a similar concentration. The cell line expressing high levels of P-glycoprotein (P-gp), COLO 320 DM, was susceptible to chemosensitization by the experimental agents for the P-gp substrates (paclitaxel, taxotere, daunorubicin, vinblastine and doxorubicin) but not for cisplatin. CaCo2 cells expressed lower levels of P-gp and were only marginally susceptible to sensitization by any one of these drugs, except in the case of sensitization by B4121 for doxorubicin and taxotere, whereas the HT-29, a P-gp negative cell line, was unaffected. The riminophenazines, especially B4121, might prove useful as combination treatment in circumventing P-gp mediated resistance of colon cancers.

In vitro investigation of the antimicrobial activities of novel tetramethylpiperidine-substituted phenazines against Mycobacterium tuberculosis.

The intra- and extracellular activities of 5 novel tetramethylpiperidine (TMP)-substituted phenazines against Mycobacterium tuberculosis H37Rv (ATCC 27294) were determined and compared with those of clofazimine and rifampicin. Two of these agents, together with clofazimine, were also tested for their activities against drug-resistant strains of M. tuberculosis. Three of the TMP-substituted phenazine compounds were significantly more active than clofazimine against M. tuberculosis, including multidrug-resistant clinical strains of this microbial pathogen, demonstrating a lack of cross-resistance between the riminophenazines and standard anti-tuberculous drugs. Using M. tuberculosis-infected monocyte-derived macrophages, all of the TMP-substituted phenazines were found to possess intracellular activity which was superior to that of both clofazimine and rifampicin. In this model of intracellular bioactivity, the experimental compounds inhibited bacterial growth at concentrations which were approximately 10-fold lower than the corresponding minimal inhibitory concentration values obtained using conventional in vitro sensitivity testing procedures. These results demonstrate that the novel TMP phenazines are active against multidrug-resistant M. tuberculosis strains, and particularly effective intracellularly.

Antimycobacterial activities of riminophenazines.

Riminophenazines were specifically developed as drugs active against Mycobacterium tuberculosis but extensive research over several decades has shown that these compounds are also active against many other mycobacterial infections, particularly those caused by Mycobacterium leprae and the Mycobacterium avium complex (MAC). Clofazimine, the lead compound in this series, is included in the regimens that are approved by the WHO for the treatment of leprosy and has contributed significantly to the control of that disease, particularly that caused by dapsone-resistant bacteria. Despite early problems, clofazimine has shown clinical efficacy in tuberculosis, in particular that caused by multiple drug resistant strains. Clofazimine does not induce resistance and also inhibits emergence of resistance to isoniazid in M. tuberculosis. The efficacy of clofazimine against MAC is more varied and the availability of better drugs has limited its use. Newer riminophenazines, such as B746 and B4157, not only showed increased anti-mycobacterial activity but also produced less skin pigmentation, which is the main drawback of this group of compounds. The most important virtues of riminophenazines, such as intracellular accumulation in mononuclear phagocytic cells, anti-inflammatory activity, a low incidence of drug resistance and slow metabolic elimination, make them attractive candidates for the treatment of mycobacterial infections. It is essential, however, to investigate the newer analogues clinically, while continuing the pursuit of alternate candidates that demonstrate higher anti-mycobacterial activity and lower rates of skin pigmentation.

Midwifery in the Belfast City Hospital.

The process of improving midwifery services for poor women in Belfast was a slow one. Traditional midwives were gradually supplanted by midwives who were trained and controlled by the medical profession, but it was many years before the problems of puerperal infection were brought under control in the new institutions.

Novel tetramethylpiperidine-substituted phenazines are potent inhibitors of P-glycoprotein activity in a multidrug resistant cancer cell line.

The multidrug resistance (MDR)-neutralizing and cytotoxic properties of 16 novel tetramethylpiperidine (TMP)-substituted phenazines were compared with those of clofazimine and B669 using a P-glycoprotein (P-gp)-expressing undifferentiated, human leukemia cell line (K562/MMB). Unchlorinated TMP-substituted phenazine molecules were more cytotoxic than their chlorinated counterparts, while the halogenated molecules, especially those with chlorine atoms at position 3 on the aniline and phenyl rings, were less cytotoxic but more effective as chemosensitizing, P-gp-neutralizing agents. One of the TMP-substituted phenazines, B4121, increased the sensitivity of K562/MMB cells to vinblastine by 100-fold. TMP-substituted phenazines are a novel class of pharmacologic anti-cancer agents with both direct cytotoxic, as well as MDR-neutralizing anti-tumor properties.

Determination of serum and tissue levels of phenazines including clofazimine.

A rapid and sensitive HPLC method is described for the analysis of synthetic phenazines, including clofazimine, from a variety of biological samples. Phenazines were extracted from serum, tissue and fat using a mixture of dichloromethane and sodium hydroxide. The drugs were then quantified on a reversed-phase C18 column using a mobile phase consisting of 594 ml of water, 400 ml of tetrahydrofuran, 6 ml of concentrated acetic acid and 0.471 g of hexanesulfonic acid. In this mobile phase, each phenazine tested had its own retention time. This allowed one phenazine to be used as an internal standard for the analysis of other phenazines. The method was validated for clofazimine [3-(4-chloroanilino)-10-(4-chlorophenyl)-2,10-dihydro-2-(isopro pylimino) phenazine] and B4090 [7-chloro-3-(4-chloranilino)-10-(4-chlorophenyl)-2, 10-dihydro-2-(2,2,6,6-tetramethylpiperid-4-ylimino)phenazine ] (VI) and shown to be accurate and precise across a broad concentration range from 0.01 to 50 micrograms/g (microgram/ml). Extraction was 100% for each agent across this range. This system was used to measure clofazimine and VI levels following their administration to rats. The pharmacokinetic profile of VI was different to that of clofazimine, with high tissue concentrations but lower fat levels.

Antituberculosis activities of clofazimine and its new analogs B4154 and B4157.

In our efforts to develop new drugs for the treatment of tuberculosis, especially that caused by multidrug-resistant strains, we investigated clofazimine (CFM) and two of its analogs, B4154 and B4157, for their antituberculosis activities. Twenty M. tuberculosis strains were tested, including 16 drug-resistant strains (strains resistant to one or more antituberculosis drugs), for their susceptibilities to these three agents. All of the strains were found to be susceptible to B4154 and B4157, and one strain showed moderate resistance to CFM. The MICs of B4154, B4157, and CFM at which 90% of strains were inhibited were 0.25, 0.12, and < or = 1.0 microgram/ml, respectively. The intracellular activities of CFM and B4157 were superior to that of B4154. The chemotherapeutic activities of the three compounds were evaluated in C57BL/6 mice. At a dose of 20 mg/kg of body weight, the activity of CFM was slightly superior to that of B4157; however, both compounds prevented mortality and caused a significant reduction in the numbers of CFU in the lungs and spleens. The animals treated with B4157 showed less pigmentation than animals treated with CFM. The chemotherapeutic activity of CFM was comparable to those of rifampin and isoniazid. Complete susceptibility of multidrug-resistant strains to CFM and B4157 and the therapeutic efficacies of these compounds against mouse tuberculosis make these drugs attractive agents for the treatment of drug-resistant tuberculosis.

Chemotherapeutic activity of clofazimine and its analogues against Mycobacterium tuberculosis. In vitro, intracellular, and in vivo studies.

Clofazimine (CFM), a riminophenazine drug, is primarily used in therapy for leprosy and Mycobacterium avium infections. With an objective of identifying drugs active against Mycobacterium tuberculosis, including those with multi-drug resistance, we investigated CFM and nine of its chemical analogues. Among these, B746 and B4101 had better activity than CFM against six drug-susceptible and nine single/multiple drug-resistant M. tuberculosis strains. B746 also showed slightly better activity than CFM against intracellular M. tuberculosis in J774A.1 macrophages and was comparable to CFM in its in vivo activity against experimental tuberculosis in C57BL/6 mice. Interestingly, it caused less pigmentation in internal organs.

Autocrine mitogen IgEGF cooperates with c-myc or with the Hcs locus during hepatocarcinogenesis in transgenic mice.

Hepatocarcinogenesis is deterministic in transgenic mice expressing in the liver gene construct Alb-DS4 that encodes autocrine growth factor IgEGF (D Stern et al. (1987), Science 235: 321-324), causing their death within 7.1 months. Hepatic expression of construct AAT-myc encoding murine c-myc causes liver cancer in 44% of the mice at 14.8 months. Cooperation of these genes was evident in CD2F1 transgenics bearing Alb-DS4 plus AAT-myc, in which accelerated hepatocellular carcinoma (HCC) formation caused death of all mice within 4.4 months. Alb-DS4 also cooperates with the Hcs locus, which in C3H/HeJ mice mediates high susceptibility to spontaneous hepatocarcinogenesis, causing accelerated formation of HCC to which mice succumbed at 5.1 months. Thus, genes that predispose to HCC formation cooperate in transgenic mice and their interaction is a key to understand mechanisms that cause liver cancer.