Decoy receptors block TRAIL sensitivity at a supracellular level: the role of stromal cells in controlling tumour TRAIL sensitivity.

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand cytokine known for its cytotoxic activity against malignantly transformed cells. TRAIL induces cell death through binding to death receptors DR4 and DR5. The inhibitory decoy receptors (DcR1 and DcR2) co-expressed with death receptor 4 (DR4)/DR5 on the same cell can block the transmission of the apoptotic signal. Here, we show that DcRs also regulate TRAIL sensitivity at a supracellular level and thus represent a mechanism by which the microenvironment can diminish tumour TRAIL sensitivity. Mathematical modelling and layered or spheroid stroma-extracellular matrix-tumour cultures were used to model the tumour microenvironment. By engineering TRAIL to escape binding by DcRs, we found that DcRs do not only act in a cell-autonomous or cis-regulatory manner, but also exert trans-cellular regulation originating from stromal cells and affect tumour cells, highlighting the potent inhibitory effect of DcRs in the tumour tissue and the necessity of selective targeting of the two death-inducing TRAIL receptors to maximise efficacy.

What service users want: a new clinic results service. Can we satisfy both patients' needs and wants?

Many clinics still have a 'no news is good news' (NNIGN) policy for clinic results. We asked our service users their preferences for obtaining results. We also designed a new clinic results service. Patients were invited to complete a service evaluation questionnaire. They were given nine options for obtaining results and asked to rate acceptability on a 1-9 scale (unacceptable to acceptable). Completed questionnaires were compared with the actual method they chose to obtain results for that visit. In all, 1000 questionnaires (561 females, 439 males) were completed. Average acceptability score was highest for mobile phone (7.7), followed by text (5.8) and letter (5.7). NNIGN (3.7) and returning for results (3.6) received the least popular ratings. When compared with the actual method chosen, mobile phone was the most popular (62%) followed by letter (17%). Only 10% of patients found NNIGN acceptable. Following the evaluation we purchased texting software and redesigned our results service. There are now four options for receiving results - texting, letter, patient telephones us and NNIGN. We believe we have been able to satisfy both patients' needs and their wishes by redesigning our service around their views.

Recent surgical experience for pulmonary tuberculosis.

Lung resection for pulmonary tuberculosis is unusual today. Over a 10-year-period 31 patients with pulmonary tuberculosis underwent thoracotomy at this Regional Centre. Five of these were for complications of known tuberculosis; two subsequently proved to be complications of pulmonary tuberculosis, and the remainder were for suspected malignancy. The clinical features, radiology, microbiology, and pathology are reviewed and the contemporary role of the surgeon in the management of pulmonary tuberculosis is examined.

Intermittent catheterisation for neuropathic urinary incontinence.

Eighty six children with neuropathic urinary incontinence who had been treated by clean intermittent catheterisation for more than five years were reviewed. Eighty five had congenital lesions, and one traumatic paraplegia. During the day, 72 (84%) patients were dry or had minor stress incontinence only, 11 were damp but controlled with pads, and only three were continuously wet. Eleven abandoned clean intermittent catheterisation, five because of poor control, four by choice despite good control, and only two because of deterioration of upper urinary tract disease. Most of them usually had bacteriuria, but only 32 developed occasional symptomatic infections. Urinary calculi occurred in six, epididymitis in three, and urethral problems in four. Upper urinary tract dilatation did not arise in a previously normal renal system in any patient during clean intermittent catheterisation. Clean intermittent catheterisation was successful in controlling wetting with few serious complications, and was well tolerated. It remains the method of choice for the management of neuropathic urinary incontinence in such children.

Cervical thymectomy in the treatment of myasthenia gravis.

Treatment modalities in myasthenia gravis consist of surgery, chemotherapy and plasmapheresis. Thymectomy can be accomplished either through a median sternotomy or through a small, transverse cervical incision. Forty patients who underwent cervical thymectomy for non-thymomatous myasthenia gravis were studied retrospectively. Twenty-six patients (65%) showed a favourable response to thymectomy and there were statistically significant improvements in myasthenic symptoms and reductions in medication requirements. Age, sex, duration of symptoms and thymic histology were not predictive of response to thymectomy. Operative mortality was zero and operative morbidity was minimal. During the last 6 years, only two of 22 patients required admission to the intensive care unit postoperatively. The postoperative hospital stay ranged from 2 to 23 days. Cervical thymectomy does not preclude later sternotomy in those patients who fail to respond favourably. We therefore recommend cervical thymectomy as the initial surgical procedure in the treatment of non-thymomatous myasthenia gravis.

Symbiotic mutants of Rhizobium meliloti that uncouple plant from bacterial differentiation.

Spontaneous mutants at a new symbiotic locus in Rhizobium meliloti SU47 are resistant to several phages and are conditionally insensitive to a monoclonal antibody to the bacterial surface, apparently because they are deficient in a wild-type exopolysaccharide. On alfalfa, the mutants do not curl root hairs, but penetrate the epidermis directly, forming nodules that contain no visible infection threads or "bacteroids," have a few bacteria in superficial intercellular spaces only and not within the nodule cells, and fail to fix nitrogen (Fix-). Evidently, infection threads are not essential for cell proliferation and nodule formation, which are here induced by a bacterial signal at a distance and uncoupled from the bacterial differentiation that normally goes on as well.

Management of neuropathic urinary incontinence in children by intermittent catheterisation.

Forty-nine children with urinary incontinence owing to neuropathic bladder were treated by intermittent catheterisation. Manometric studies to determine urethral closing pressures and intravesical pressure/volume relationships were performed before or during treatment in all children. Cystography and intravenous urography were carried out at the beginning of treatment and intravenous urography was repeated after treatment for at least 12 months. Routine long-term antibacterial therapy was not used. With a 3-hourly catheterisation regimen a total of 46 (93%) children achieved day-time control but 27 (55%) did so only with the help of propantheline or imipramine or both of these. Night-time control was also substantially improved in 43 (87%) children. The manometric studies enabled a reliable prediction to be made on whether drugs would be required to achieve success. One child with an undilated urinary tract before treatment developed unilateral dilatation owing to mechanical problems during treatment. Upper urinary tract dilatation which was present before treatment in 20 children (33 kidneys) disappeared or improved in all. Early renal failure in 2 children also responded favourably. The technique had to be abandoned in 2 children.