British Association of Urological Surgeons (BAUS) consensus document: management of bladder and ureteric injury

Injuries to the bladder and ureter are uncommon but usually require prompt urological management. Due to their infrequent nature, Urologists maybe unfamiliar with managing these acute problems and may not work in specialist centres with readily available expertise in open and abdominal surgery. We aim to provide advice in the form of a consensus statement led by the Female, Neurological and Urodynamic Urology (FNUU) Section of the British Association of Urological Surgeons (BAUS), in consultation with BAUS members and consultants working in units throughout the UK, to create a comprehensive management pathway and a series of statements to aid clinicians.     

Cholecystokinin and neurotensin mRNAs are differentially expressed in subnuclei of the ventral tegmental area

Immunohistochemical studies of ventral tegmental area (VTA) neurons indicate that individual cells can contain dopamine as well as the neuropeptide neurotransmitters cholecystokinin (CCK) and neurotensin (NT). We have defined the distribution of the cells expressing the mRNAs encoding these two dopamine cotransmitter peptides in each of the subnuclei of the ventral tegmental area, and quantitated the extent of expression of each gene by using in situ hybridization methods. These studies reveal significant differences in the patterns of expression of each of these two genes within various subdivisions of the VTA. The rostral linear nucleus contained numerous CCK positive cells, some of which appeared to express preproCCK-mRNA at a very high level, but this nucleus contained relatively few NT-expressing cells. The parabrachialis pigmentosus contained numerous NT and CCK positive cells. The paranigralis and interfascicularis nuclei displayed positive CCK cells but with expression at only modest levels. NT cells were very few in these nuclei. The caudal linear nuclei contained the highest number of NT-expressing neurons and these cells expressed very high levels of NT mRNA. The selective distribution of these peptide genes within the VTA subnuclei may have specific consequences. Studies of the connectivity of neurons in the VTA show that the different subnuclei of this region project to several functionally and architectonically different regions of the cerebral cortex and subcortically to nuclei related to the limbic system. Results from our study show very prominent expression of CCK mRNAs in those subnuclei that project heavily to the prefrontal, other cortical areas, and the amygdaloid complex. The NT gene is expressed prominently in those subnuclei of VTA that project heavily to the entorhinal cortex and amygdaloid complex. These results provide support for a differential role for the NT-expressing neurons than that of CCK-expressing neurons of VTA in "reward" mechanisms and in drug-seeking and motivational behavior. These observations could be applied to create working hypotheses and experimental paradigms to test the differential functional activity of the subdivisions of VTA and their potential roles in the pathogenesis and treatment of drug-seeking behavior and other neuropsychiatric disorders.     

Biochemical and antitumor activity of trimidox,a new inhibitor of ribonucleotide reductase

Trimidox (3,4,5-trihydroxybenzamidoxime), a newly synthesized analog of didox (N,3,4-trihydroxybenzamide) reduced the activity of ribonucleotide reductase (EC 1.17.4.1) in extracts of L1210 cells by 50% (50% growth-inhibitory concentration, IC₅₀) at 5 M, whereas hydroxyurea, the only ribonucleotide reductase inhibitor in clinical use, exhibited an IC₅₀ of 500 M. Ribonucleotide reductase activity was also measured in situ by incubating L1210 cells for 24 h with trimidox at 7.5 M, a concentration that inhibits cell proliferation by 50% (IC₅₀) or at 100 M for 2 h; these concentrations resulted in a decrease in enzyme activity to 22% and 50% of the control value, respectively. Trimidox and hydroxyurea were cytotoxic to L1210 cells with IC₅₀ values of 7.5 and 50 M, respectively. Versus ribonucleotide reductase, trimidox and hydroxyurea yielded IC₅₀ values of 12 and 87 M, respectively. A dose-dependent increase in life span was observed in mice bearing intraperitoneally transplanted L1210 tumors. Trimidox treatment (200 mg/kg; q1dx9) significantly increased the life span of mice bearing L1210 leukemia (by 82 in male mice and 112% in female mice). The antitumor activity appeared more pronounced in female mice than in male mice. Viewed in concert, these findings suggest that trimidox is a new and potent inhibitor of ribonucleotide reductase and that it is a promising candidate for the chemotherapy of cancer in humans.Abbreviations Didox N,3,4-trihydroxybenzamide - MTT {3-[4,5-dimethyl-thiazo-2yl]}-2,5-diphenyl tetrazolium bromide - PBS phosphate-buffered saline - trimidox 3,4,5-trihydroxybenzamidoxime HCl     

Back pain and collapse associated with receding subarachnoid blockade

Purpose

Back pain and sudden loss of consciousness during recovery from spinal anesthesia are rare. Severe pain may raise fears of serious neurological damage and result in inappropriate management. Bladder distention may present in this way and clinicians should be alert to this possibility and communicate this to nursing staff.

Clinical features

A lumbar spinal anesthetic was performed during a volunteer study, using 15 mg hyperbaric bupivacaine in a healthy 31 yr old man. During recovery, five hours later, as the block regressed to the L_1–2 level, he complained of acute, severe back pain and briefly lost consciousness secondary to profound bradycardia. Bladder cathetherization yielded 900 mL urine with immediate and complete relief of symptoms.

Conclusion

Severe pain secondary to bladder overdistention in the presence of neuroaxial blockade may be referred to the thoracolumbar area, mediated by intact sympathetic afferents. As the saccral parasympathetic supply remains paralyzed, there is no subjective sensation of bladder stretching. If untreated, bladder distention can lead to excessive supraspinal parasympathetic outflow resulting in vasovagal syncope.     

External laryngocele

Laryngocele is an extremely rare condition. A case of external laryngocele is being reported along with a brief review on its pathogenesis, clinical presentation and management.     

Osteocutaneous radial forearm free flaps. The necessity of internal fixation of the donor-site defect to prevent pathological fracture

BACKGROUND: Osteocutaneous radial forearm free flaps have fallen from favor due to pathological fractures of the radius. The purposes of this study were to propose a means to decrease the rate of pathological fracture by prophylactic fixation of the donor-site defect and to evaluate this technique biomechanically. METHODS: Two groups of ten matched pairs of fresh-frozen cadaveric radii were harvested. In Group 1, an eight-centimeter length of radius comprising 50 percent of the cross-sectional area of the bone was removed to simulate an osteocutaneous radial forearm donor-site defect. This defect was created in one member of each pair, with the other bone in the pair left intact. In Group 2, both members of the ten matched pairs of radii had identical defects created as previously described. However, one radius in each pair had a twelve-hole, 3.5-millimeter dynamic compression plate placed across the segmental defect. In each group, five matched pairs were tested to failure in torsion and five matched pairs were tested to failure in four-point bending. RESULTS: In Group 1, the intact radius was a mean of 5.7 times stronger in torsion and 4.2 times stronger in four-point bending than the radius with the segmental resection. In Group 2, the radius that was ostectomized and fixed with a plate was a mean of 4.0 times stronger in torsion and 2.7 times stronger in four-point bending than the ostectomized radius. CONCLUSIONS: Removal of an eight-centimeter segment from the radius dramatically decreased both torsion and bending strength. Application of a plate over the defect in the radius significantly restored the strength of the radius (p = 0.01).     

The pancreatic ductal epithelium serves as a potential pool of progenitor cells

Abstract:  With the increasing success of islet transplantation, β-cell replacement therapy has had renewed interest. To make such a therapy available to more than a few of the thousands of patients with diabetes, new sources of insulin-producing cells must become readily available. The most promising sources are stem cells, whether embryonic or adult stem cells. Clearly identifiable adult pancreatic stem cells have yet to be characterized. Although considerable evidence suggests their possibility, recent lineage-tracing experiments challenge their existence. Even in light of these lineage-tracing experiments, we suggest that evidence for neogenesis or new islet formation after birth remains strong. Our work has suggested that the pancreatic duct epithelium itself serves as a pool for progenitors for both islet and acinar tissues after birth and into adulthood and, thus, that the duct epithelium can be considered 'facultative stem cells'. We will develop our case for this hypothesis in this perspective.     

Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer.

PURPOSE: The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2) -positive disease. PATIENTS AND METHODS: Forty-two patients with HER2-positive disease with operable breast cancer were randomly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. The primary objective was to demonstrate a 20% improvement in pCR (assumed 21% to 41%) with the addition of trastuzumab to chemotherapy. The planned sample size was 164 patients. RESULTS: Prognostic factors were similar in the two groups. After 34 patients had completed therapy, the trial's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy. pCR rates were 25% and 66.7% for chemotherapy (n = 16) and trastuzumab plus chemotherapy (n = 18), respectively (P = .02). The decision was based on the calculation that, if study continued to 164 patients, there was a 95% probability that trastuzumab plus chemotherapy would be superior. Of the 42 randomized patients, 26% in the chemotherapy arm achieved pCR compared with 65.2% in the trastuzumab plus chemotherapy arm (P = .016). The safety of this approach is not established, although no clinical congestive heart failure was observed. A more than 10% decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms, respectively. CONCLUSION: Despite the small sample size, these data indicate that adding trastuzumab to chemotherapy, as used in this trial, significantly increased pCR without clinical congestive heart failure.     

Towards an effective social care model for arrest referral: Implications for criminal justice interventions for problem drug users

Aims: To assess an operational model for arrest-referral schemes that successfully facilitates the entry of highly entrenched and chaotic problem drug users into specialist drug-treatment services. Methods: (1) An examination of case records from a voluntary arrest-referral service (SMART CJS) based across the Thames Valley region of the UK during 2002-2003; (2) Probablistic database linkage of agency case records with the National Drug Treatment Monitoring System (NDTMS); (3) participant observation and semi-structured interviews with agency staff.

Findings: Over half of problem drug users (58%) maintained contact with the scheme following initial contact in police custody. Referrals were made to a wide range of social-care services in addition to specialist drug treatment to include prison-based services, housing support and primary care. This model was able to demonstrate very high levels of specialist drug treatment uptake (53%) following referral. There was a close relationship between the average length of time a problem drug user entered treatment following contact in police custody and the average length of an active case file. Such an approach was considered essential to maintain motivation with clients.

Discussion: This social care model has operational validity in ensuring treatment uptake of recidivist problem drug-using offenders. Continuity of care alongside referrals addressing wider community harms including social exclusion and public health should be encouraged.