bluuebunny/crossref_metadata_2025 huggingface dataset:
The expanding role of the transplant pharmacist in the multidisciplinary practice of transplantation
Authors: Martin Jill E , Zavala Edward Y
Published: June 2004

Abstract:  Introduction:  The burgeoning clinical discipline and growth of organ transplantation has resulted in an expansion in the number of healthcare specialists to support clinical care and research. The past 10 yrs have seen a dramatic increase in the number of immunosuppressive agents and other medications used in transplantation, resulting in more complex medication regimens and greater potential for interactions, adverse effects and increased costs.

Purpose:  To determine how transplant pharmacists are being integrated into transplant clinical practice. Transplant centres were identified through UNOS Transplant Administrators Committee list serve. A survey was then distributed via e‐mail to 159 individuals representing 118 solid organ transplant centres.

Results:  Forty‐one (35%) of the 118 centres responded, with 36 evaluable surveys. Of the 36 centres, 28 (78%) had transplant pharmacist support and eight did not have a pharmacist dedicated to transplant (two of the eight were recruiting). A majority of the respondents had multi‐organ transplant responsibilities. Eighty‐six per cent of pharmacists were involved in kidney transplant, 71% in liver, 50% in pancreas, 25% in heart, and 7% in lung. Pharmacist salaries were most often funded by a department of pharmacy (74%), followed by college of pharmacy (12%), transplant centre (8%) and department of surgery (6%). Almost all of the pharmacist's clinical practice time focused on post‐transplant care (99%). The average percentage of the pharmacist's time was: 43% inpatient, 15% outpatient, 14% research, 6% other transplant related, and 22% non‐transplant related. Of the 28 pharmacists, 25 had a PharmD degree, two a BS and one had a PhD in Pharmacy. The average number of organs transplanted among the responding centres was 99 kidneys, 45 livers, 28 pancreas, 14 heart, and 26 lungs. The number of transplants did not differ between the programmes with pharmacist clinical support vs. those without designated pharmacist support.

Conclusion:  The survey indicates that many solid organ transplant centres have incorporated transplant pharmacists into the multidisciplinary transplant clinical team. Transplant pharmacists are funded most often by the hospital pharmacy. Most transplant pharmacists spend the majority of their time in clinical practice, but also play a key role in research.
Soluble interleukin 2 receptor (sIL‐2R) levels in renal transplant recipients
Authors: Mehta Rajil , Shah Gaurang , Adler William , Kittur Dilip
Published: June 2004

Abstract:  Background:  Allograft rejection is associated with T cell activation. T cell activation leads to secretion of soluble IL‐2 receptor and elevated serum soluble IL‐2 receptor (sIL‐2R) levels. However, the clinical implication of individual elevated sIL‐2 receptor levels is unclear. We followed levels of sIL‐2R pre‐ and post‐transplantation to determine if sIL‐2R levels predict rejection episodes or degree of graft function.

Materials and methods:  Serum samples of 12 patients who underwent living or cadaveric renal transplant were followed weekly with serial sIL‐2R levels. These levels were followed until the serum creatinine reached a baseline. Of the 12 patients, three patients developed delayed graft function. The remaining nine patients were followed for a period of 3 months. Sera of these nine patients in the initial 3 months post‐transplant were monitored for sIL‐2R levels. For comparison, sIL‐2R levels were also measured in 150 healthy volunteers and five dialysis patients.

Results:  Recipients undergoing severe rejection episodes had higher overall serum levels of sIL‐2R (1515 ± 496 U/mL) as compared with recipients who had stable renal transplants and no episodes of rejection (698 ± 333 U/mL) (P = 0.034). Comparison of sIL‐2R ratios (post‐transplant sIL‐2R level/pre‐transplant sIL‐2R level) revealed that ratios of 0.6 or higher were more frequently seen in patients who subsequently underwent severe rejection episodes. Dialysis patients were found to have higher sIL‐2R levels (2605 ± 1312 U/mL) compared with renal transplant patients (1047 ± 192 U/mL) (P < 0.001) and healthy volunteers (349 ± 185 U/mL) (P < 0.001).

Conclusion:  Our results suggest that individual levels of sIL‐2R are not predictive of rejection in the early post‐transplant period, but s‐IL2R ratios greater than 0.6 may be predictive of severe rejection episodes.
Cross‐species comparison of gene expression between human and porcine tissue, using single microarray platform – preliminary results
Authors: Shah Gaurang , Azizian Maria , Bruch David , Mehta Rajil , Kittur Dilip
Published: June 2004

Abstract:  Introduction:  Xenotransplantation is a potential solution for inadequate supply of donor organs. Pigs are considered the ideal donor for kidney transplantation to human recipients, therefore it is important to understand the gene regulation in the porcine organs. Oligonucleotide array technology has been utilized largely for human, mouse and rat gene expression studies only. Its use with porcine genes has not been reported. We investigated the possibility of studying gene regulation in porcine kidney with a human GeneChip microarray® platform.

Methods:  To assess the feasibility of using a single microarrray platform for comparison of expressing data across different species (human and pig), we compared the gene expression profiles of human brain, human kidney and pig kidney using the Affymetrix U‐133 A human GeneChip®, which contains probes for 22 283 genes. Kidney biopsies from pigs and humans, with normal histology, were used to obtain RNA for porcine and human samples, while a commercially available adult whole cortex total RNA sample (Clontech) was used for the human sample. We assessed the intensity ratio for housekeeping and tissue specific genes. To examine the potential for non‐specific binding to create false positive errors in our data, we compared the expression profiles in our experiments to a number of public databases.

Results:  There were approximately the same number of genes expressed at higher levels in the pig kidney as in the human kidney and human brain. The major differences in gene expression were found for genes with tissue specific patterns of expression. Eighty genes were increased in human brain vs. human and pig kidney samples. Two hundred and eighty genes were increased in human and pig kidney vs. human brain samples. Of the top 25 genes increased in pig kidney compared with human brain, we were able to cross‐reference 18 genes to the Unigene and SAGE public databases. We confirmed the expected higher levels of expression in the kidney in 18 genes. Of the top 25 genes increased in human brain vs. pig kidney, we were able to cross‐reference 20 genes to the Unigene and SAGE databases and confirm the expected higher expression levels in brain in 17 genes with three inconclusive genes.

Conclusion:  This low level of false positive findings, at this preliminary stage, supports the concept of using human GeneChip® microarray platform to compare gene expression profiles between pig and human tissues in the absence of a porcine microarray platform. Our study opens a new avenue into the analysis of porcine genes relevant to xenotransplantation.
Cutaneous Alternaria infection in renal transplant recipients: a report of two cases with an unusual mode of transmission
Authors: Kazory A. , Ducloux D. , Reboux G. , Blanc D. , Faivre B. , Chalopin J.‐M. , Piarroux R.
Published: June 2004

Abstract: We report two cases of cutaneous alternariosis in renal transplant recipients. The diagnosis was made by mycologic and histologic examination. The patients were treated with itraconazole. In one patient who had undergone surgical resection of the cutaneous lesion along with antifungal treatment, the follow‐up period was uneventful with no signs of recurrence. In the other patient, surgical excision of the lesion was not performed prior to antifungal therapy. The lesion disappeared following treatment but local recurrence was observed 1.5 years later with an unfavorable evolution despite administration of the second course of therapy. Resection of the lesion and prolongation of the treatment resulted in a satisfactory course with no signs of local recurrence over a follow‐up period of 4.5 years. Interestingly, both of the patients had a previous history of a mild traumatic event with a stretcher in our outpatient clinic where the follow‐up visits were made. A vast mycologic survey was then made in our department, which disclosed that some of the stretchers were contaminated by the fungi and could have potentially served as the reservoirs and vectors for the transmission of the fungus.
No association between serum levels of insulin‐like growth factor‐I, vascular endothelial growth factor, prolactin and clinicopathological characteristics of breast carcinoma after surgery
Authors: Sancak B. , Coskun U. , Gunel N. , Onuk E. , Cihan A. , Karamercan A. , Yildirim Y. , Ozkan S.
Published: June 2004

Abstract

Background:  Angiogenesis is essential for tumour growth and metastasis. Vascular endothelial growth factor (VEGF) has been suggested as the major angio­genic factor in breast carcinoma. Both insulin‐like growth factor‐I (IGF‐I) and prolactin are involved in the progression of breast cancer at least partly by stimulating angiogenesis.

Aim: The aim of the present study was to investigate the association between serum IGF‐I, VEGF and prolactin levels and clinicopathological characteristics of breast carcinoma.

Methods:  Serum IGF‐I, VEGF and prolactin levels were measured in breast cancer patients and controls and these levels were compared with well‐known clinicopathological characteristics of breast carcinoma, including tumour size, axillary lymph node and oestrogen/progesterone receptor status, tumour grade and disease stage.

Results:  Serum prolactin, VEGF and IGF‐I levels were found to be similar in breast cancer patients and control subjects (P > 0.05). When the patients were divided into groups according to their tumour size, axillary lymph node status, tumour grade, oestrogen/progesterone receptor status and disease stage, no significant differences in serum prolactin, VEGF and IGF‐I levels were found among the groups (P > 0.05).

Conclusions:  The present study failed to demonstrate an association between serum levels of VEGF, IGF‐I and prolactin and well‐known clinicopathological characteristics of breast carcinoma. (Intern Med J 2004; 34: 310−315)
Prospective audit of conversion from regular to lispro insulin during routine clinical care
Authors: Lunt H. , Kendall D. , Moore M. P. , Scott R. S. , Cole D. , Frampton C. M. , Cullens M.
Published: June 2004

Abstract

Background: Randomized controlled trials show that lispro insulin has the potential to improve glycaemic control. Observational, practice‐based studies provide information that is complementary to that obtained from randomized controlled trials and results of both types of studies are of relevance when advising patients of likely outcomes during routine clinical care.

Aims: This prospective audit aimed to determine whether conversion from regular (short‐acting, soluble) preprandial insulin to lispro during routine clinical care improved glycated haemoglobin.

Methods: Eligible patients were those using regular insulin before main meals and a basal neutral protamine Hagedorn (NPH) insulin. Study group patients were those who chose to convert to lispro insulin. Patients who elected not to change their regimen were used as a comparison group. Follow up was for a minimum of 1 year.

Results: Glycated haemoglobin (HbA1c) and body mass index showed no change in either the study or comparison groups. Post‐hoc analysis revealed that the patients most likely to improve their HbA1c on lispro were those with a higher baseline HbA1c. Patients using lispro reported a decreased frequency of hypoglycaemia and improved convenience of use.

Conclusions: Administration of lispro insulin was perceived by patients as convenient to use and was also associated with less hypoglycaemia when compared with the use of regular insulin. There was, however, no improvement in HbA1c. This finding may be informative when advising patients during routine clinical care of the likely metabolic outcome of changing their insulin regimen. (Intern Med J 2004; 34: 320−323)
Management of chronic hepatitis C virus infection: a new era of disease control
Authors: Teoh N. C. , Farrell G. C.
Published: June 2004

Abstract

The management of chronic viral hepatitis has changed significantly with the availability of effective antiviral agents. There is now a high probability that timely intervention can arrest development of cirrhosis, thereby preventing mortality from portal hypertension, liver failure and liver cancer. This two‐part review discusses the implications of this new era of antiviral therapy for physicians. The present review is about chronic hepatitis C virus (HCV); a similar review that considers the treatment of hepatitis B virus will be published in a later issue of theInternal Medicine Journal. Chronic HCV infection is common, but fibrotic progression of liver disease is slow and variable; many infected persons never develop cirrhosis. Case selection for antiviral therapy is crucial. The most effective therapy is a pegylated (long‐acting) interferon with ribavirin. Sustained viral response (SVR) (absent viraemia 6 months after completing treatment) can be obtained in 40−60% of individuals infected with genotype 1 and in approximately 67% with genotype 4 after 12 months of treatment. Response rates are higher (75−85%) with genotypes 2 and 3 after only 6 months of treatment. Late relapse is negligible after SVR. This viral cure reverses hepatic fibrosis, reduces the risk of liver failure and of hepato­cellular carcinoma. Combination therapy requires a supportive setting to minimize the impact of side‐effects and maximize therapeutic effectiveness. Overall management of HCV‐infected persons must also embrace measures to improve quality of life by preventing or dealing with psychosocial issues and advocating lifestyle changes to counter comorbidity from alcohol, central obesity and insulin resistance. These latter factors favour fibrotic disease progression, complications of cirrhosis (such as hepatocellular carcinoma) and development of type 2 diabetes mellitus, as well as eroding the chances of SVR with antiviral therapy. (Intern Med J 2004; 34: 324−337)
Development of a regimen for rapid initiation of perhexiline therapy in acute coronary syndromes
Authors: Philpott A. , Chandy S. , Morris R. , Horowitz J. D.
Published: June 2004

Abstract

Perhexiline is a prophylactic anti‐anginal agent that ameliorates the metabolic basis for myocardial ischaemia and is increasingly used in the management of acute coro­nary syndromes. No intravenous preparation is available and usual oral loading regimens require 2−3 days to achieve therapeutic drug levels. Two patients presenting to hospital with single‐dose over­dosage of perhexiline (6500 mg and 1000 mg, respectively) provided a basis for examining the safety of large single dosage of perhexiline and associated time‐course of drug levels. Neither patient had previously taken perhexiline. Peak plasma perhexiline concentrations occurred within 12 h of ingestion and were 2.58 and 0.50 mg/L, respectively (therapeutic range 0.15−0.60 mg/L). The first patient developed transient nausea and vomiting; the second patient had no adverse effects. Subsequently, a series of 10 patients with acute coronary syndromes received an 800‐mg loading dose. Peak concentrations occurred within 12 h postdose; the mean levels achieved were 0.40 ± 0.16 mg/L (standard error of the mean). No serious adverse effects were seen. Two patients reported transient nausea or vomiting within 24 h of the loading dose. The utility of this rapid loading regimen for incremental suppression of myocardial ischaemia remains to be assessed. (Intern Med J 2004; 34: 361−363)
Neural activation during experimental allodynia: a functional magnetic resonance imaging study
Authors: Maihöfner Christian , Schmelz Martin , Forster Clemens , Neundörfer Bernhard , Handwerker Hermann O.
Published: June 2004

Pain induced by gentle stroking, i.e. dynamic–mechanical allodynia, is one of the most distressing symptoms of neuropathic pain. The underlying neuronal pathways are still a matter of debate. Here, we investigated the cortical activations associated with dynamic‐mechanical allodynia in an experimental human pain model by functional magnetic resonance imaging (fMRI). Large and stable areas of brush‐evoked allodynia were induced in 11 healthy subjects by topical capsaicin (2.5%, 30 min) application following local heating (45 °C for 5 min), thus combining both physical and chemical sensitization. During the fMRI experiments, allodynia was rekindled by local heat application (40 °C for 5 min) immediately before the allodynia testing. Brushing the untreated forearm (control condition) led to activations of the contralateral primary somatosensory cortex (S1), contralateral parietal association cortex (PA), bilateral secondary somatosensory cortices (S2) and insula (contralateral). Brushing the allodynic skin was painful and the cortical responses were partially overlapping with those induced by the nonpainful brush stimulation. Additionally, the contralateral inferior frontal cortex (IFC) and the ipsilateral insula were activated. Direct comparison between nonpainful brushing and brush‐evoked allodynia revealed significant increases in blood oxygenation level‐dependent (BOLD) signals in contralateral S1, PA, IFC and bilateral S2/insula during allodynia. This study highlights the importance of a cortical network comprising S1, PA, S2/insula and IFC in the processing of dynamic–mechanical allodynia in the human brain. Furthermore, it demonstrates that the combined heat/capsaicin model can be used successfully in the exploration of brain processes underlying stimulus‐evoked pain.
Zoledronic acid induces apoptosis and inhibits adhesion to mineralized matrix in prostate cancer cells via inhibition of protein prenylation
Authors: Coxon Jonathan P. , Oades Grenville M. , Kirby Roger S. , Colston Kay W.
Published: June 2004

OBJECTIVE

To investigate effects of zoledronic acid on apoptosis and adhesion to mineralized matrix in prostate cancer cells, to quantify these actions, and to elucidate some of the underlying molecular mechanisms, in terms of dependence on caspase activation and involvement of protein prenylation.

MATERIALS AND METHODS

DU145 and PC‐3 prostate cancer cell lines were used; cells were treated with zoledronic acid, with or without several other reagents, to investigate its mechanism of action. Apoptosis was detected using a cell‐death detection enzyme‐linked immunosorbent assay. Adhesion was measured by seeding cells onto mineralized dentine inserts for 24 h, and counting cells after washing.

RESULTS

Apoptosis depended on time and dose; there was significant apoptosis with higher concentrations of zoledronic acid (100 µmol/L) after 24 h of exposure, and in DU145 cells with concentrations as low as 1 µmol/L after 72 h of exposure. The apoptotic effect was diminished by co‐treating with a broad‐spectrum caspase inhibitor, Z‐VAD‐FMK. Zoledronic acid at 1 µmol/L also significantly inhibited cell adhesion to the mineralized matrix. The lipid isoprenoid analogue geranylgeraniol reduced the apoptotic and anti‐adhesive effects of zoledronic acid to a greater degree than farnesol. There was also apoptosis and inhibition of adhesion with direct inhibitors of prenylation, e.g. manumycin A and GGTI‐298. C3 exoenzyme, an inhibitor of RhoA, inhibited adhesion but did not cause apoptosis.

CONCLUSION

Zoledronic acid induces apoptosis in prostate cancer cells via a caspase‐dependent mechanism, and at concentrations as low as 1 µmol/L it also inhibits adhesion of cells to mineralized matrix. These effects appear to be exerted via inhibiting G‐protein prenylation and in particular geranylgeranylation.
Intravesical resiniferatoxin decreases spinal c‐fos expression and increases bladder volume to reflex micturition in rats with chronic inflamed urinary bladders
Authors: Dinis Paulo , Charrua Ana , Avelino António , Cruz Francisco
Published: June 2004

OBJECTIVE

To evaluate the effect of intravesical resiniferatoxin on spinal c‐fos expression and bladder volume at reflex micturition in rats with chronic urinary bladder inflammation.

MATERIALS AND METHODS

Of three groups of female Wistar rats, group 1 received cyclophosphamide (75 mg/kg body weight) intraperitoneally every third day (cyclophosphamide is an antitumoral agent that induces bladder inflammation after urinary excretion of its metabolite, acrolein); group 2 comprised sham‐inflamed rats that received saline instead of cyclophosphamide, and group 3 received cyclophosphamide, as group 1, every third day but plus 10 nmol/L resiniferatoxin intravesically, through a urethral catheter, at 7 days. At 8 days, under urethane anaesthesia, a needle was inserted in the bladder dome and saline infused at 6 mL/h for 2 h. Finally the animals were perfusion‐fixed through the ascending aorta with 4% paraformaldehyde. Transverse sections cut from L6 spinal cord segments were immunoreacted for Fos protein and positive cells in the dorsal horn counted. In a further set of equal groups the bladders were prepared in the same way under urethane anaesthesia and after 30‐min of stabilization, saline was infused at 6 mL/h and the volume evoking reflex micturition determined.

RESULTS

The mean (Sd) number of positive c‐fos cells per spinal cord section was 85 (21), 42 (9) (P = 0.002) and 55 (10) in groups 1 to 3, respectively; the values for group 2 and 3 were similar (P = 0.22) and statistically less than that of group 1 (P = 0.02). Reflex micturition occurred at, respectively, 0.26 (0.09), 0.49 (0.18) and 0.52 (0.11) mL, being similar in group 2 and 3 (P = 0.74) but lower in group 1 (P = 0.003).

CONCLUSION

Intravesical resiniferatoxin decreases c‐fos expression and increases bladder capacity in chronically inflamed rat bladders. These findings suggest that desensitizing the vanilloid receptor type 1 by intravesical resiniferatoxin is relevant to the treatment of pain and voiding frequency in patients with chronic inflammatory bladder conditions.
Pelvic fracture‐associated urethral injuries in girls: experience with primary repair
Authors: Dorairajan Lalgudi N. , Gupta Harendra , Kumar Santosh
Published: June 2004

OBJECTIVE

To present our experience with four urethral injuries in females accompanying a pelvic fracture, managed with primary repair or realignment of the urethra.

PATIENTS AND METHODS

There were three teenage girls and one adult (22 years old). All the patients had complete urethral injuries associated with a pelvic fracture from accidents. They were managed by immediate suprapubic cystostomy followed by repair or realignment of the urethra over a catheter on the same day. The catheter was removed after 3 weeks and a voiding cysto‐urethrogram taken. Thereafter they were followed with regular urethral calibration.

RESULTS

All patients voided satisfactorily with a good stream; three were fully continent and the fourth had transient stress urinary incontinence. One patient needed dilatation at 2 months and another visual internal urethrotomy at 5 months. At a mean (range) follow‐up of 33 (9–60) months all the patients had a normal voiding pattern and were continent; none developed vaginal stenosis.

CONCLUSION

Primary repair of the urethra, and if that is impossible, simple urethral realignment over a catheter, is the procedure of choice for managing female urethral injury associated with a pelvic fracture. The procedure has the additional advantage of reducing the risk of vaginal stenosis.
The role of glycoproteins in calcium oxalate crystal development
Authors: Grases Felix , Isern Bernat , Perelló Joan , Costa‐Bauzá Antonia
Published: June 2004

OBJECTIVE

To assess the effects of a glycoprotein (mucine) on calcium oxalate crystal development in different conditions and situations, to clarify some of its possible effects.

MATERIALS AND METHODS

Crystallization was assessed using a batch system in presence of mucine suspensions, by kinetic‐turbidimetric measurements, and using a flow system in the presence of retained agglomerates of mucine, evaluating the precipitated calcium oxalate.

RESULTS

In batch conditions low mucine concentrations (<15 mg/L) inhibited calcium oxalate nucleation and higher concentrations (<250 mg/L) inhibited calcium phosphate nucleation, whereas at high concentrations there was also promotion. The presence of an aggregate of mucine in the flow system provoked calcium oxalate monohydrate crystallization at 0.691 µg/h per mg of mucine. In flow conditions pyrophosphate at 11.5 µmol/L caused a decrease of 84% in the calcium oxalate crystallized on mucine, 1.32 mmol/L of citrate a decrease of a 83%, 20 mg/L of pentosan polysulphate a decrease by 80%, and 7.58 µmol/L phytate totally prevented the crystallization of calcium oxalate on mucine.

CONCLUSION

All substances inhibiting calcium oxalate crystallization with the capacity to interact with calcium ions also have crystallization promoting properties when they are at sufficiently high concentrations, because of their capacity to form agglomerates or the insolubility of their calcium salts.
Patient‐adjusted intermittent electrostimulation for treating stress and urge urinary incontinence
Authors: Nissenkorn Israel , Shalev Moshe , Radziszewski Piotr , Dobronski Piotr , Borkowski Andrzej , De Jong Peter R.
Published: June 2004

OBJECTIVE

To assess the safety and efficacy of pelvic floor muscle electrostimulation (ES) in women with stress urinary incontinence (SUI) or mixed UI (MUI, urge and interstitial cystitis), using a new portable electrostimulator (Miniaturo, Biocontrol Medical Inc., Yehud, Israel) which delivers different forms of stimulation for treating these two conditions.

PATIENTS AND METHODS

For SUI the stimulator is activated on demand only by a sudden increase in intra‐abdominal pressure; for frequency and urgency a milder, continuous ES is used. The intensity of ES can be adjusted according to the patient's sensation. Women were enrolled into the study after satisfying inclusion criteria and pad testing; 23 participated in two study groups, i.e. 16 with SUI and seven with MUI (severe frequency, urgency and urge, and mild SUI). The pelvic floor muscles were stimulated through an electrode inserted paraurethrally, positioned similarly in all patients. In patients with SUI and MUI a pressure sensor was also inserted into the rectum, to record intra‐abdominal pressure. Stimulation was applied for 1–4 h in patients with SUI and for 6 h in those with MUI. The evaluation was based on urinary symptoms (frequency, urgency, leaking episodes), quality‐of‐life questionnaires and pad tests at baseline and during stimulation.

RESULTS

All patients in both groups improved significantly; of the 16 patients with SUI, nine were completely dry during ES, and the remaining seven had a reduced mean pad weight, from 23 to 6 g (74%). There was no significant reduction in pad weight after sham ES (17 g before vs 24.2 g after). In four patients with SUI who continued ES for 4 h the mean cumulative stimulation time (calculated from the stimulator memory) was 3 min (1.3% of 4 h). In the MUI group there were no leakage episodes during ES and significant reductions in voiding variables (Student's t‐test) in all. The mean (Sd) voiding frequency, urinary urgency and leaking episodes decreased from 8.1 (4.2) to 1.9 (1.5), 6.4 (2.3) to 0.7 (1.3) and 2.1 (0.7) to 0.7 (0.5) (all P < 0.001), respectively.

CONCLUSIONS

The concept of this ES system for treating UI is promising; this study supports the efficacy of this form of ES but no conclusions about clinical efficacy are possible at this stage, and thus a trial to evaluate the safety and efficacy of this implantable device is ongoing.
Predictive value of primary Gleason pattern 4 in patients with Gleason score 7 tumours treated with radical prostatectomy
Authors: Khoddami Seyed M. , Shariat Shahrokh F. , Lotan Yair , Saboorian Hossein , McConnell John D. , Sagalowsky Arthur I. , Roehrborn Claus G. , Koeneman Kenneth S.
Published: June 2004

OBJECTIVE

To examine whether Gleason score (GS) 3 + 4 and 4 + 3 cancers at radical prostatectomy behave differently and whether this behaviour is independently associated with prostate cancer outcome.

PATIENTS AND METHODS

From July 1994 to December 2002 309 consecutive men who had a radical retropubic prostatectomy for clinically localized disease had final GS 7 tumours in their prostatectomy specimen. Statistical analyses, including multivariate logistic regression, were used to evaluate the association between variables, i.e. standard preoperative features, stage, PSA progression, standard pathological variables, metastasis and death.

RESULTS

In all, 215 patients (70%) had a final GS of 3 + 4 and 94 (30%) of 4 + 3. A final GS of 4 + 3 was associated with clinical stage T2 disease (P = 0.024), a higher biopsy GS (P < 0.001), seminal vesicle involvement (P < 0.001), positive surgical margins (P = 0.036), lymphovascular invasion (P = 0.018), metastases to regional lymph nodes (P = 0.008), higher preoperative serum prostate‐specific antigen (PSA) (P = 0.042), and percentage positive biopsy cores (P = 0.006). In univariate analysis, patients with GS 4 + 3 had a significantly higher risk of biochemical progression than those with GS 3 + 4 (P = 0.002). The 5‐year actuarial risk of biochemical progression was 17% and 35% for GS 3 + 4 and 4 + 3, respectively (P = 0.0016). In a standard postoperative multivariate analysis, only preoperative PSA and metastases to regional lymph nodes were associated with PSA progression (P < 0.001 and 0.002, respectively). However, patients with final GS 4 + 3 had a shorter PSA doubling time after progression than those with GS 3 + 4 (P = 0.009).

CONCLUSIONS

Tumours with a final GS of 4 + 3 are more aggressive than GS 3 + 4 tumours. Recognising the distinction in GS 7 between predominant 4 vs 3 scores after radical prostatectomy should improve the ability of clinicians to counsel patients. The GS 4 pattern deserves further molecular study.
Complexed prostate specific antigen (PSA) reduces unnecessary prostate biopsies in the 2.6–4.0 ng/mL range of total PSA
Authors: Parsons J. Kellogg , Brawer Michael K. , Cheli Carol D. , Partin Alan W. , Djavan Robert
Published: June 2004

OBJECTIVE

To compare the performance of complexed prostate‐specific antigen (cPSA) to total PSA (tPSA) and percentage free PSA (f/tPSA) in the diagnosis of prostate cancer for the tPSA range 2.6–4.0 ng/mL.

PATIENTS AND METHODS

Consecutive men scheduled for prostate biopsy were enrolled prospectively at 14 different sites in two multicentre studies in Europe and the USA. Serum obtained before biopsy was tested with the ACS:180 and Immuno 1 tPSA and cPSA assays (Bayer Diagnostics, Tarrytown, NY, USA) and the Access fPSA and tPSA assays (Beckman, Inc., San Diego, CA, USA). Receiver operating characteristics (ROC) curves were generated to compare the diagnostic performance of tPSA, cPSA and f/tPSA.

RESULTS

Of 316 men with a tPSA of 2.6–4.0 ng/mL, 82 (26%) were diagnosed with prostate cancer on biopsy. ROC analysis of all 316 men showed an area under the curve (AUC) for cPSA of 0.63, significantly greater than the AUC for tPSA of 0.56 (P = 0.008). At a sensitivity of 95%, threshold values of 2.3 ng/mL for cPSA and 2.73 ng/mL for tPSA provided specificities of 20.1% and 9.8%, respectively. f/tPSA was only available for 205 of the 316 (65%) men and the AUC for cPSA was 0.63, and did not significantly differ from the f/tPSA AUC of 0.64 (P = 0.58).

CONCLUSIONS

As a single test, cPSA provides improved specificity over tPSA and comparable specificity to f/tPSA for detecting prostate cancer, and may reduce the number of unnecessary prostate biopsies in the 2.6–4.0 ng/mL tPSA range.
Reconstruction of the sympathetic pathway projecting to the prostate, by nerve grafting in the dog
Authors: Hyochi Nobuhiko , Kihara Kazunori , Arai Gaku , Kobayashi Tsuyoshi , Sato Kenji
Published: June 2004

OBJECTIVES

To examine the possibility of nerve grafting to repair the sympathetic pathway projecting to the prostate, as contraction of the prostate is known to be controlled by the sympathetic pathway via the hypogastric nerve (HGN), and injuries to the pathway cause significant disturbances in prostatic secretion.

MATERIALS AND METHODS

In six dogs both of the HGNs were partly removed and immediately repaired with an autologous nerve graft. The left HGN was repaired with a colonic (autonomic) nerve graft and the right with a genitofemoral (somatic) nerve graft. Twenty months after surgery the reconstruction of the sympathetic pathway was assessed by measuring contraction of the prostate after stimulating the lumbar splanchnic nerves (LSNs).

RESULTS

Nine of the 17 right LSNs stimulated elicited prostatic contractions. After transecting the left HGN five of these nine responses were restored. Seven of the 11 left LSNs stimulated elicited prostatic contractions; after transection of the left HGN four of these seven responses were preserved.

CONCLUSION

The sympathetic pathways via the HGN to the canine prostate can be reconstructed by nerve grafting, regardless of the use of autonomic or somatic nerve grafts, and the cross‐innervation mechanism from the LSN to the prostate can also be repaired.
Genetics for urologists
Authors: Rochester Mark A. , Brewster Simon F.
Published: June 2004

The ability to study the molecular and genetic basis of disease with an increasingly wide and sophisticated armoury of techniques will lead to enhanced understanding of the causes of disease, and so to the progression of gene‐directed therapy. The challenge ahead is in refining these therapeutic techniques to provide efficient and safe delivery of genetic material or gene‐silencing agents.
Building a Strong Foothold in an Emerging Market: A Link Between Resource Commitment and Environment Conditions*
Authors: Luo Yadong
Published: June 2004

ABSTRACT This study examines how MNEs align resource commitment with environmental conditions (challenges and opportunities) when they invest in a foreign emerging market. MNEs often face a dilemma in allocating resources to this environment: without this commitment, they cannot build a strong competitive foothold; yet with over‐commitment, there is excessive economic exposure. Our analysis of MNEs in a major emerging market suggests that resource commitment is an inverse function of market uncertainty and this inverse link is stronger for less strategically proactive MNEs. Resource commitment is also an increasing function of market opportunities and this function is stronger for firms emphasizing demand‐side (as opposed to cost‐side) gains. In addition, in a highly volatile industry, resource commitment is negatively associated with cultural distance, but in a relatively stable industry, it is positively associated with cultural distance. And finally, as foreign subsidiaries become older, the influence of cultural distance on resource commitment is weakened.
Too Busy To Serve? An Examination of the Influence of Overboarded Directors
Authors: Harris Ira C. , Shimizu Katsuhiko
Published: June 2004

ABSTRACT Overboarded directors (i.e., those serving on too many boards) have come under recent attack. The accusation is that such directors are ‘stretched’ by several directorships and therefore cannot fulfil their governance responsibility. This study investigates the impact of overboarded directors upon key strategic decisions such as corporate acquisitions. Based on our examination of acquisition outcomes, we found that such directors are important sources of knowledge and enhance acquisition performance. Moreover, they represent an important complement to inside and non‐overboarded outside directors.
Organizational Task Environments: An Evaluation of Convergent and Discriminant Validity*
Authors: Harris Randall D.
Published: June 2004

ABSTRACT The organizational task environment (OTE) construct is evaluated using a large, independent sample. A general measurement model for three latent variables, munificence, dynamism and complexity is constructed for confirmatory factor analysis. This model is then tested for both convergent and discriminant validity using a multitrait‐multimethod matrix approach. The OTE model in this study demonstrates convergent validity, but it does not exhibit discriminant validity. The results of this study do not provide support for one of the key components of construct validity. Measurement issues are discussed, as well as the implications of this study for the organizational theory and strategic management disciplines.
Nonlinear Flow Between Permeable Disks Using Computer‐Extended Series Method
Authors: Rudraiah N. , Dinesh P. A.
Published: June 2004

The problem of two‐dimensional, steady, nonlinear flow of an incompressible, viscous fluid between two parallel permeable disks is studied using the computer‐extended series solution (CESS). The limitation of the classical regular perturbation technique (RPT) in solving this problem is highlighted and the CESS method in conjunction with Padé approximation is advocated to analyze the problem for much larger values of suction/injection Reynolds number R and to achieve higher accuracy. The skin‐friction coefficient and coefficient of pressure distribution are evaluated for different values of R. The advantages of using CESS method over the RPT and numerical technique are discussed.
Nonlinear Eigenvalue Problems in the Stability Analysis of Morphogen Gradients
Authors: Lou Y. , Nie Q. , Wan F. Y. M.
Published: June 2004

This paper is concerned with several eigenvalue problems in the linear stability analysis of steady state morphogen gradients for several models of Drosophila wing imaginal discs including one not previously considered. These problems share several common difficulties including the following: (a) The steady state solution which appears in the coefficients of the relevant differential equations of the stability analysis is only known qualitatively and numerically. (b) Though the governing differential equations are linear, the eigenvalue parameter appears nonlinearly after reduction to a problem for one unknown. (c) The eigenvalues are determined not only as solutions of a homogeneous boundary value problem with homogeneous Dirichlet boundary conditions, but also by an alternative auxiliary condition to one of the Dirichlet conditions allowed by a boundary condition of the original problem. Regarding the stability of the steady state morphogen gradients, we prove that the eigenvalues must all be positive and hence the steady state morphogen gradients are asymptotically stable. The other principal finding is a novel result pertaining to the smallest (positive) eigenvalue that determines the slowest decay rate of transients and the time needed to reach steady state. Here we prove that the smallest eigenvalue does not come from the nonlinear Dirichlet eigenvalue problem but from the complementary auxiliary condition requiring only to find the smallest zero of a rational function. Keeping in mind that even the steady state solution needed for the stability analysis is only known numerically, not having to solve the nonlinear Dirichlet eigenvalue problem is both an attractive theoretical outcome and a significant computational simplification.
Napoleon's Lost Legions: French Prisoners of War in Britain, 1803–1814
Authors: DALY GAVIN
Published: June 2004

During the Napoleonic Wars, over 100,000 French prisoners of war were held captive in Britain. These prisoners remain a marginal group in the military history of the period, yet they represent a key turning point in the history of European prisoners of war, and their predicament offers insights into the nature of the French Revolution. This article considers the treatment and experiences of French prisoners, and in particular seeks to understand the circumstances surrounding their long‐term captivity. Unlike eighteenth‐century prisoners of war, prisoners of the Napoleonic Wars remained captive for the duration of the conflict, unable to return home through the traditional means of prisoner exchange or officer parole. This radical departure from the past gave rise to the modern practice of interning prisoners of war for the entire duration of a war. This historic shift was, on the one level, a result of the actions of one man – Napoleon Bonaparte. Yet, as this article highlights, it must also be understood as part of the long‐term social and cultural legacy of the French Revolution.
No Secrets Between ‘Special Friends’: America's Involvement in British Economic Policy, October 1964–April 1965
Authors: ROY RAJ
Published: June 2004

The war in Vietnam has dominated the historiography of American foreign relations in the 1960s, and in particular the foreign policy of President Lyndon Johnson. The military difficulties endured by the United States in Vietnam, together with a number of international economic crises, have all been conclusive evidence, in the eyes of diplomatic historians, of the decline in the power and influence of the United States during this period. Historical treatments of the relationship between Britain and the United States have been equally gloomy, with the visible tensions and ill‐feeling between Lyndon Johnson and the British prime minister, Harold Wilson, being highlighted. Through an examination of the involvement of the United States in the British government's domestic economic policy in late 1964 and early 1965, this article argues that the United States, far from simply managing the process of decline, had come to use new and more subtle techniques to wield considerable power and influence in the domestic politics of its allies. Moreover, whilst the conduct of the war in Vietnam may have generated personal tensions at the highest level, common interests ensured that Britain and the United States continued to enjoy an extremely close relationship in the economic sphere.
Beyond ‘Euroland’: British trade unions, the single currency and European integration
Authors: Mulhearn Chris
Published: June 2004

British trade unions have differing perspectives as to the desirability of UK membership of the eurozone. This paper provides a critical review of the spectrum of union views and highlights key points of disagreement and areas of common ground. An agenda for further reflection upon the euro by the unions is also offered. Finally, the paper considers union positions on the implications of the wider process of European integration for industrial relations.
The effects of age discrimination legislation on workplace practice: a New Zealand case study
Authors: Wood Geoffrey , Harcourt Mark , Harcourt Sondra
Published: June 2004

This article explores the effects of the legal prohibition of age discrimination in New Zealand, based on a survey of the recruiting practices of individual organisations. Its findings indicate that many firms continue to breach the law through a continued emphasis on age during the recruitment process. Age‐related information is directly or indirectly requested from a sizeable percentage of job applicants. The findings highlight the importance of the socio‐economic context in which legislation is enacted. As with unwritten rules, the impact of law in a specific context is inevitably circumscribed by the deeply embedded nature of practice, especially if enforcement is lax.
Rice versus fish revisited: On the integrated management of floodplain resources in Bangladesh
Authors: Shankar Bhavani , Halls Ashley , Barr Julian
Published: June 2004

Disproportionately little attention has been paid to the dry season trade‐off between rice and (inland capture) fish production on the floodplains of Bangladesh, compared to the same trade‐off during the flood season. As the rural economy grows increasingly dominated by dry‐season irrigated rice production, and floodplain land and water come under ever‐increasing pressure during the dry winter months, there is an urgent need to focus attention on these dry months that are so critical to the survival and propagation of the floodplain resident fish, and to the poor people that depend on these fish for their livelihood. This article examines three important dry‐season natural resource constraints to floodplain livelihoods in Bangladesh, and finds a common factor at the heart of all three: rice cultivation on lands at low and very low elevations. The article articulates the system interlinkages that bind these constraints and the long‐run trend towards irrigated rice cropping on lower‐lying lands, and suggests a management approach based on locally tailored strategies to arrest this trend. Apart from its direct relevance to the floodplains of Bangladesh, which support more than 100 million people, these lessons have relevance for river floodplain systems elsewhere in the developing world, notably the Mekong Delta.
Informality in mineral resource management in Asia: Raising questions relating to community economies and sustainable development
Authors: Lahiri‐Dutt Kuntala
Published: June 2004

Informal mining activities provide livelihoods for millions of poor in mineral‐rich developing countries. Yet, they continue to remain one of the least understood areas in mineral resource management. While its poverty reduction potential is acknowledged, the heterogeneous forms of mining that come under its purview are not well discussed. This article aims to draw attention to the politics of definition by briefly introducing the reader to the nomenclature currently used to describe such mining activities. Then the article examines the nature of informality that justifies the name, and then illustrates the claim by documenting a range of informal mining practices in India with cited examples from other Asian countries. It illustrates the variations in social‐economic, technical and legal characteristics, by putting such mining in a community and participatory framework. Finally, the article discusses ways to move towards sustainable development with community participation in mineral‐rich areas of developing countries.
Extensive size homoplasy at a microsatellite locus in the Japanese bumblebee,Bombus diversus
Authors: YOKOYAMA Jun , FUKUDA Tatsuya , YOKOYAMA Akiko , NAKAJIMA Maki
Published: June 2004

An extensive size homoplasy was found at microsatellite locus B11 of the bumblebee,Bombus diversus, in northern to central Honshu, Japan. A total of 16 alleles of different nucleotide sequences in five length morphs was obtained at B11 for this species. Of these alleles, five were 141 base pairs (bp) in length, five were 137 bp and four were 133 bp. Allele diversity in each length morph was high compared with previous studies. It is noteworthy that this extensive size homoplasy was found in a relatively small geographic area, in contrast to results from previous studies. Reconstruction of a median‐joining network revealed the complicated evolutionary process of the locus, involving insertion/deletion and point mutations. Preliminary estimation of the mutation rate of the B11 locus inB. diversusgives a value comparable to those estimated from experimentalDrosophilapopulations. Effects of the extensive size homoplasy in population genetic studies is discussed.