Recombinant human parvovirus B19 vectors

In an attempt to exploit the remarkable tissue-tropism of the human parvovirus B19 to target human hematopoietic cells of the erythroid lineage, recombinant human adeno-associated virus 2 genomes were encapsidated in parvovirus B19 capsids. Although efficient transduction of primary human hematopoietic cells in the erythroid lineage occurred, a low-level of transgene expression in non-erythroid cells was also detected. These studies suggest that cell surface expression of P antigen, the primary receptor for parvovirus B19, is necessary but not sufficient for parvovirus B19 vector-mediated transduction of human hematopoietic cells. These studies also suggest the existence of a putative cell surface co-receptor, which is required for successful infection of human hematopoietic cells by parvovirus B19.     

Cytological diagnosis of nonulcerative penile neoplasms: report of two cases

Nonulcerative penile mass lesions are rare. Pathological diagnosis of these lesions would traditionally be a biopsy. We report two such primary penile lesions which were diagnosed by fine-needle aspiration cytology (FNAC). Both lesions were present in the shaft and were diagnosed as squamous cell carcinoma (SCC). The first patient had a recurrence on the penile stump of partial amputation without any ulceration. The second had a primary urethral carcinoma on the terminal penile shaft infiltrating the corpora cavernosa dorsally. Open biopsies were avoided in both cases. FNAC was associated with very little and tolerable discomfort. There were no complications. The aspirate yield was sufficient for cytological diagnosis. FNAC of nonulcerated penile lesions is safe, well tolerated, and capable of providing a cytological diagnosis. Hence, it is a very useful outpatient procedure and could be the procedure of choice for diagnosis.     

Use of ivabradine for treatment of junctional ectopic tachycardia in post congenital heart surgery

Cardiac surgeries especially involving crux of the heart as performed in tetralogy of Fallot (TOF) and pulmonary stenosis are mainly responsible for junctional ectopic tachycardia (JET). Diversified antiarrhythmic agents have been used in an impressive way to treat JET but showed suboptimal efficacy and varied associated adverse effects. But, ivabradine has proved as final crusader for its treatment. We report our initial experience of 4 cases in last 6 months with ivabradine in the management of postoperative JET. Encouraged by various reports and our increasing experience with ivabradine in heart failure population, we have moved to ivabradine as the first drug of choice for postoperative JET. Bradycardia was the only significant adverse effect in our series. The availability of atrial and ventricular pacing wires or at least transvenous temporary pacing should be ensured before starting ivabradine.     

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.     

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.