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.

Saccharomyces cerevisiae elongation factor 2 is phosphorylated by an endogenous kinase.

Mammalian cells contain a Ca2+/calmodulin-dependent protein kinase that specifically phosphorylates and inactivates elongation factor 2 (EF-2) in response to hormones and other agents which increase intracellular Ca2+ concentrations. Therefore, it has been proposed that the rate of translation in mammals is regulated by EF-2 phosphorylation. In the present study, EF-2 purified from the yeast Saccharomyces cerevisiae is shown to be a substrate for the mammalian EF-2 kinase. Furthermore, evidence was obtained using two-dimensional gel electrophoresis and peptide mapping which suggests that yeast EF-2 is a substrate for an endogenous kinase which phosphorylates the same site as the mammalian EF-2 kinase. Based on these findings, we propose that in yeast as in higher eukaryotes, the protein synthesis elongation cycle is regulated by phosphorylation of EF-2.

Purification and assay of cell-invasive form of calmodulin-sensitive adenylyl cyclase from Bordetella pertussis.

An invasive form of the CaM-sensitive adenylyl cyclase from Bordetella pertussis can be isolated from bacterial culture supernatants. This isolation is achieved through the use of QAE-Sephadex anion-exchange chromatography. It has been demonstrated that the addition of exogenous Ca2+ to the anion-exchange gradient buffers will affect elution from the column and will thereby affect the isolation of invasive adenylyl cyclase. This is probably due to a Ca2(+)-dependent interaction of the catalytic subunit with another component in the culture supernatant. Two peaks of adenylyl cyclase activity are obtained. The Pk1 adenylyl cyclase preparation is able to cause significant increases in intracellular cAMP levels in animal cells. This increase occurs rapidly and in a dose-dependent manner in both N1E-115 mouse neuroblastoma cells and human erythrocytes. The Pk2 adenylyl cyclase has catalytic activity but is not cell invasive. This material can serve, therefore, as a control to ensure that the cAMP which is measured is, indeed, intracellular. A second control is to add exogenous CaM to the Pk1 adenylyl cyclase preparation. The 45-kDa catalytic subunit-CaM complex is not cell invasive. Although the mechanism for membrane translocation of the adenylyl cyclase is unknown, there is evidence that the adenylyl cyclase enters animal cells by a mechanism distinct from receptor-mediated endocytosis. Calmodulin-sensitive adenylyl cyclase activity can be removed from preparations of the adenylyl cyclase that have been subjected to SDS-polyacrylamide gel electrophoresis. This property of the enzyme has enabled purification of the catalytic subunit to apparent homogeneity. The purified catalytic subunit from culture supernatants has a predicted molecular weight of 45,000. This polypeptide interacts directly with Ca2+ and this interaction may be important for its invasion into animal cells. Finally, the technique for purifying the catalytic subunit by SDS-polyacrylamide gel electrophoresis may prove useful in studying the interaction of the adenylyl cyclase with other components produced by the bacteria, as well as the interaction of the enzyme with eukaryotic target cells.

Artificial bladder replacement: a new design concept [see comment].

An effectively functioning artificial bladder would be useful after cystectomy because of the ease of insertion and the availability to all patients. In this report, we describe a new design concept based on negative pressure drainage of the kidneys and active voiding, and we present the results of testing this device. Although previous prosthetic bladders have had difficulties with renal failure from hydronephrosis, infection from retention of urine, and encrustation of the luminal surface, the current artificial complete bladder system addresses these problems.

Renal transplantation in patients with spina bifida.

OBJECTIVES: Renal transplantation in patients with spina bifida is not commonly performed, although these patients have a high incidence of end-stage renal disease. METHODS: Between February 1989 and December 1991, we performed 5 cadaveric renal transplants in 4 patients with spina bifida. There were 3 male patients and 1 female patient with a mean age of 22.5 years (range, 10 to 36 years). All patients had lumbar myelomeningoceles repaired shortly after birth. Three patients were wheelchair-bound due to their neurologic deficit. Prior to renal transplantation, management of neuropathic bladder dysfunction consisted of ileal conduit (1 patient), "clam" cystoplasty with clean intermittent self-catheterization (CISC; 1 patient), and CISC alone (2 patients). RESULTS: In this series, 1 patient died of fungal septicemia 6 weeks postoperatively. One patient underwent transplantation again following primary nonfunction of his original allograft. Serum creatinine levels were 56, 91, and 120 mmol/L, respectively, after 18 months' follow-up. CONCLUSIONS: This article demonstrates the feasibility of cadaveric renal transplantation in selected patients with end-stage renal failure and spina bifida. We currently recommend that these patients not be excluded from gaining the benefits of renal transplantation.

Primary lymphoma of the bladder: a report of three cases.

BACKGROUND: Primary lymphoma of the bladder is rare and its management is an evolving field. AIMS: To highlight primary lymphoma of the bladder as a possible diagnosis in cases of bladder neoplasm and to illustrate the currently favoured management options. METHODS: Three cases of primary bladder lymphoma are reported and management is reviewed. RESULTS: Each of the three cases was managed differently with each management approach yielding a favourable outcome. CONCLUSION: Chemotherapy combined, if necessary, with surgery or radiation therapy, should be the standard of care, depending on the full histological diagnosis.

Manifestations of Von Hippel Lindau syndrome: a retrospective national review.

INTRODUCTION: Von Hippel Lindau (VHL) disease is a syndrome that is defined by variety of tumours such as cerebellar haemangioblastomas, renal cell carcinomas, phaeochromocytomas, pancreatic adenomas and ear, nose and throat (ENT) adenomas. This disease is often genetic and inherited in an autosomal dominant fashion, and can present in childhood, adolescence or adult life. This study describes the presentation, natural history and manifestations of patients attending our institutions with this condition. We aim to highlight the importance of screening in diagnosing the manifestations of VHL. METHODS: A retrospective review was performed on all patients diagnosed with VHL and coded as such by the national Hospital Inpatient Enquiry Scheme at Beaumont Hospital Dublin and Cork University Hospital. This was performed over a 20 years period between 1989 and 2009. Age, sex, mode of presentation, presence or absence of end stage kidney disease and genotype were documented. Presence or absence of the characteristic tumours of VHL was also recorded, as were the initial presenting features of these tumours. RESULTS: Thirty-six patients were diagnosed with VHL. These patients ranged from 18 to 78 years old. Three patients were members of the Irish travelling community. The most frequent mode of presentation was altered neurological signs (40%), with a significant proportion presenting with haematuria (23%). Patients diagnosed prior to 1995 were more likely to have presented with significant complications of VHL, while those diagnosed after this time were more likely to have been diagnosed via screening. Genetic testing was performed on 17 patients; those who did not have genetic testing performed were more likely to have been diagnosed prior to the era of genetic testing. Thirty-one patients had received screening for complications of VHL including renal cell carcinomas, central nervous system (CNS) haemangioblastomas and phaeochromocytomas. The patients who did not receive any screening presented with neurological symptoms. CONCLUSION: Beaumont Hospital Dublin and Cork University Hospital are tertiary referral centres for nephrology, urology and neurosurgery and deals with a significant proportion of patients diagnosed with VHL in Ireland. This study highlights the significant burden of this illness and emphasizes the importance of screening for these renal/CNS and ENT complications. This study also highlights the importance of family screening in diagnosing this condition.

Synchronous sigmoid and caecal cancers together with a primary renal cell carcinoma.

BACKGROUND: Multiple primary neoplasms, a common clinical entity, can be classified as synchronous or metachronous. Renal cell carcinoma, in particular, is associated with a high rate of multiple primary neoplasms. METHODS: We report a case of a 67-year-old Caucasian woman, who was admitted with history of bleeding per rectum. We conducted a literature review of metachronous and synchronous multiple primary neoplasms. RESULTS: Colonoscopy revealed a 3 cm tumour in the caecum and a small sigmoid tubulovillous polyp. Staging computed tomography showed a non-enhancing mass in the upper pole of the right kidney. Following a radical nephrectomy/right hemicolectomy, microscopy demonstrated a renal cell carcinoma. Follow-up colonoscopy visualised a mucosal irregularity at the site of the previous sigmoid polyp, with biopsies confirming invasive adenocarcinoma. Patient underwent a total colectomy with an ileo-rectal anastamosis. CONCLUSION: Multiple primary neoplasms are a well-recognised clinical entity. This report emphasises the need for a comprehensive evidence-based work-up in all cancer cases, especially when dealing with renal cell carcinoma, to look for coexisting metachronous/synchronous primary neoplasms.

An unusual case of cancer of the urachal remnant following repair of bladder exstrophy.

INTRODUCTION: We report the first case of cancer of the urachal remnant following repair of bladder exstrophy, in a renal transplant recipient. METHOD: A retrospective review of this clinical case and the associated literature were performed. CONCLUSION: This unusual case highlights two very rare entities. Bladder exstrophy has an incidence of 1 in 50,000 newborns, whereas urachal cancer accounts for less than 1% of all bladder tumours.

Evidence that the adenylate cyclase secreted from Bordetella pertussis does not enter animal cells by receptor-mediated endocytosis.

Bordetella pertussis, the pathogen responsible for whooping cough, produces a calmodulin-sensitive adenylate cyclase. Several investigators have shown that the partially purified adenylate cyclase is capable of entering animal cells and elevating intracellular cAMP levels (Confer and Eaton: Science 217:948-950, 1982; Shattuck and Storm: Biochemistry 24:6323-6328, 1985). However, the mechanism for entry of the catalytic subunit of this adenylate cyclase into animal cells is unknown. It has been reported that the B. pertussis adenylate cyclase extracted from bacterial cells with urea does not enter animal cells by receptor-mediated endocytosis. There is, in addition to the cell associated form of the B. pertussis adenylate cyclase, a cell-invasive form of the enzyme secreted into the bacterial culture media. The properties of the cell-associated and secreted enzymes are significantly different (Masure and Storm: Biochemistry 28:438-442, 1989). In this study, we report evidence that the secreted form of the B. pertussis adenylate cyclase enters animal cells by a mechanism distinct from receptor-mediated endocytosis.

A model of human small intestinal absorptive cells. 1. Transport barrier.

The Caco-2 cell culture model of human small intestinal absorptive cells was used to investigate transepithelial transport. Transport of permeability markers such as mannitol demonstrated that Caco-2 monolayers became less permeable with increasing age in culture. Cells were routinely used for transport studies between day 18 and day 32. A transport index was determined for each compound by calculating the ratio of transport of the molecules under investigation to transport of an internal standard such as the permeability marker mannitol. Comparison of transport rates at 4 and 37 degrees C was a simple approach for differentiating primary transport mechanisms (passive paracellular, passive transcellular, or transporter-mediated) but must be coupled with additional experimental manipulations for definitive determination of transport pathways. Compounds predicted to undergo predominantly paracellular transport (mannitol, FITC, PEG-900, and PEG-4000), transporter-mediated transcellular transport (glucose, biotin, spermidine, or alanine), or lipophilic transcellular transport (alprenolol, propranolol, clonidine, or diazepam) showed differential effects of temperature on rates of transport as well as the transport index.

A screening procedure for the intracellular expression of native proteins by Saccharomyces cerevisiae: discrimination of diphtheria toxin-resistant mutants.

A general method is described for screening Saccharomyces cerevisiae colonies for the intracellular expression of native proteins. Colonies are replicated onto nitrocellulose membranes and yeast cell walls are removed enzymatically. The resulting spheroplasts are rapidly lysed by placing chromatography paper soaked in hypotonic buffer on the membranes. Intracellular proteins released by spheroplast lysis are bound in situ to the nitrocellulose under non-denaturing conditions and potentially can be examined using enzymatic or immunologic methods. For example, in the present study colonies were screened for the presence of elongation factor 2 (EF-2) that can be [32P]ADP-ribosylated by diphtheria toxin and [32P]NAD+. Recognition by the toxin requires the presence in EF-2 of the unique post-translationally modified histidine derivative, diphthamide. The procedure described here reliably discriminates between wild-type yeast colonies and mutant colonies that do not synthesize diphthamide. In addition to facilitating the study of diphthamide biosynthesis in yeast, the more general application of this procedure will enable the screening of colonies with assays that require native proteins.

Use of the artificial urinary sphincter in the management of severe incontinence in females.

AS 792 and AS 800 sphincters were implanted in 31 female patients with incontinence due to various causes including neurologic dysfunction, recurrent stress incontinence, spinal cord trauma and pelvic trauma. Continued continence has been achieved in 21 of these patients. Erosions required removal of the device in the ten other patients. The AS 800 model has significant modifications that allow activation and deactivation without additional operative procedures. Satisfactory continence can be achieved in properly selected patients. The integrity of the vesicovaginal surgical plane is the key to success. Patients with multiple operations are the most difficult to manage and delayed activation is mandatory. Intermittent catheterization can be safely done and mechanical reliability is good.

Isolation of a protein fraction from Bordetella pertussis that facilitates entry of the calmodulin-sensitive adenylate cyclase into animal cells.

Bordetella pertussis, the pathogen responsible for whooping cough, releases a soluble calmodulin-sensitive adenylate cyclase into its culture medium. Several investigators have shown that the partially purified adenylate cyclase is capable of entering animal cells and elevating intracellular cAMP levels [Confer, D. L., & Eaton, J. W. (1982) Science 217, 948-950; Shattuck, R. L., & Storm, D. R. (1985) Biochemistry 24,6323-6328]. However, the mechanism for entry of the catalytic subunit of the adenylate cyclase into animal cells is unknown. Recently, it was determined that the purified catalytic subunit of the enzyme is unable to enter animal cells [Masure, H. R., Oldenburg, D. J., Donovan, M. G., Shattuck, R. L., & Storm, D. R. (1988) J. Biol. Chem. 263, 6933-6940]. On the basis of these data and other observations, we hypothesized that the culture medium of B. pertussis contains one or more additional polypeptides which facilitate entry of the adenylate cyclase catalytic subunit into animal cells. In this study, we report that a cell-invasive preparation of B. pertussis adenylate cyclase was rendered noninvasive after passage through a wheat germ lectin-agarose column. A fraction was eluted from the wheat germ lectin-agarose column with N-acetyl-D-glucosamine. This fraction, when combined with the noninvasive adenylate cyclase, was able to restore the ability of the adenylate cyclase preparation to enter neuroblastoma cells and increase intracellular cAMP levels. Furthermore, the fraction eluted from the wheat germ lectin-agarose column was found to be trypsin and chymotrypsin sensitive, suggesting that this material was proteinaceous.(ABSTRACT TRUNCATED AT 250 WORDS)

Autologous calvarial and iliac onlay bone grafts in miniature swine.

Calvarial bone has been reported to be superior to iliac bone for onlay bone grafting due to decreased resorption. This study evaluated the physical, histologic, and radiographic characteristics of calvarial and corticocancellous iliac onlay bone grafts in nine Pitman-Moore miniature swine at 2 weeks, and at 1-, 2-, 4-, 6-, 7-, 8-, 10-, and 12-month intervals. Compared with iliac grafts, the calvarial onlay grafts had more than a twofold greater radiographic density. Statistical analysis of the mature grafts using the standard of estimated means of the bone graft volumes revealed 85% retention of the calvarial grafts compared with 34% retention of the grafted iliac bone. There was no subjective difference in the rate or degree of revascularization between the two grafted materials.

Is mechanical bowel preparation necessary in patients undergoing cystectomy and urinary diversion?

OBJECTIVE: To compare the surgical outcome in patients with or with no bowel preparation before cystectomy and ileal conduit urinary diversion, specifically assessing local and systemic complications. PATIENTS AND METHODS: All patients undergoing cystectomy and ileal conduit urinary diversion between January 1991 and December 1999 were assessed retrospectively. Twenty-two receive no bowel preparation (group 1) and were compared with 64 who had (group 2). Patients had similar demographic characteristics, stage and grade of tumour. Patients in group 2 received a standard 4-day bowel preparation and group 1 received no lavage or enemas. All patients underwent a standard iliac and obturator lymph node dissection, and cystoprostatectomy or anterior exenteration and ileal conduit urinary diversion. All patients received intraoperative metronidazole and gentamicin intravenously, and two further doses after surgery. RESULTS: Deaths after surgery were comparable in the two groups (two in group 1 and four in group 2) and the incidence of wound infection was similar (three and seven, respectively). There were no significant differences between the respective groups for fistula and anastomotic dehiscence (two and six) or sepsis (three and six). Group 2 had a higher incidence of wound dehiscence (one) than in group 1 (none). The incidence of prolonged postoperative ileus was lower in group 1 (one vs 12), as was the length of hospital stay (31.6 days vs 22.8 days). CONCLUSIONS: Bowel preparation had no advantage for the surgical outcome but it increased the length of hospital stay.

Experimental evaluation of expanded polytetrafluoroethylene for reconstruction of orbital floor defects.

OBJECTIVE: This study evaluates the efficacy of a medical grade expanded polytetrafluoroethylene (e-PTFE) sheet for reconstruction of the orbital floor. MATERIALS AND METHODS: Orbital floor defects were created in 10 domestic sheep and reconstructed with the 1-mm thick e-PTFE sheet. The surgical sites were evaluated for the development of enophthalmos and biocompatibility at 2 weeks, and at 1-, 2-, 4-, and 6-months intervals. RESULTS: The results of this indicate that the e-PTFE material has excellent handling characteristics, provides stability to correct surgically created enophthalmos, and causes essentially no foreign body reaction. CONCLUSION: Expanded polytetrafluoroethylene proved to be an excellent alloplastic material for the repair of orbital floor defects in this experimental study.