The signalling pathway for BCG-induced interleukin-6 production in human bladder cancer cells

Intravesical bacillus Calmette-Guerin (BCG) is currently the therapy of choice for superficial bladder cancer with a 60-70% response rate. Induction of cytokine production (e.g. IL-6, etc.) by BCG has been found in patient's urine in vivo as well as bladder cancer cell lines. However, the signalling mechanisms are still unclear. In this study, we investigated the effect of BCG on cAMP production and its role in regulating interleukin-6 expression in the human bladder cancer cell line, MGH. After 1 hr exposure to BCG, IL-6 gene expression in MGH cells increased by 2.5-3-fold and cAMP production increased by 8-10-fold in a time- and dose-dependent manner. BCG-induced cAMP production was inhibited by both antifibronectin antibody and an adenylate cyclase inhibitor, SQ22536 in a dose-dependent way. In the presence of SQ22536, IL-6 expression in MGH cells was also greatly reduced. Furthermore, cAMP-dependent kinase inhibitors H7 and HA1004 also inhibited BCG-induced IL-6 expression in MGH, with HA1004 being much less effective than H7. Thus, BCG induces cAMP production and may regulate interleukin-6 expression partially via a cAMP-dependent pathway in human bladder cancer cells.     

An assessment of the Down syndrome antenatal screening policies of East and West Gloucestershire between 1993 and 1999.

This retrospective observational study of registered pregnancies in Gloucestershire between 1 April 1993 and 31 March 1999 compares the impact of different Down syndrome antenatal screening policies on detection and amniocentesis rates. The screening policies in East and West Gloucestershire are based on early second-trimester maternal serum and maternal age screening, respectively. Maternal serum screening can identify a greater proportion of pregnancies affected by Down syndrome than a programme founded on age-based amniocentesis and 20 weeks' ultrasound. In addition, maternal serum screening of women older than 34 approximately halves the number of amniocenteses performed to detect one affected fetus. However, the proportion of pregnant women who have amniocentesis is nearly doubled by offering serum screening to women aged over 24 years. These findings of the impact of established second-trimester screening policies in low-risk populations provides an useful benchmark to compare the performance of screening procedures that will be introduced in the United Kingdom over the next 3 years.     

Bone anchored hearing aids: a second fixture reduces auditory deprivation in Cambridge

Bone anchored hearing aids are well established for canal atresia, otosclerosis and chronic suppurative otitis media. Refinements in technique to maximise gain while keeping the complications to a minimum are desirable. This study was taken up in order to explore the potential advantage of a second or spare fixture placed at the time of primary surgery. A group of patients who underwent BAHA insertion at The Emmeline Centre for Cochlear Implants and Bone Anchored Hearing Aids, Addenbrookes hospital, Cambridge, UK with the placement of a spare fixture between 1999 and 2002 were compared to those patients with one fixture BAHA undertaken from 1991. Main outcome measures were complications encountered and duration of disability, (i.e. loss of hearing while waiting for new fixture placement). Both groups had similar incidence of complications, but the group with two fixtures suffered a shorter period of disability when a fixture failed. In our experience the use of second or spare fixture reduces the duration of disability. It engenders no additional complications with minimal extra cost. This paper was presented at 24th Politzer society meeting, Amsterdam, September 2003.     

Could the presence of a Carhart notch predict the presence of glue at myringotomy?

The Carhart notch is a dip in the bone conduction at 2000 Hz without a corresponding dip in the air conduction. The main objective of this study was to establish how reliable is the presence of the Carhart notch in a preoperative audiogram in predicting the presence of glue at myringotomy. A prospective study has been carried out in 50 children presenting with glue ear to find out the association between the Carhart notch and the presence of glue at myringotomy. Children were seen before the operation and an audiogram and tympanogram were carried out. Myringotomy was carried out in 95 ears and the presence or absence of glue was recorded. The significance of the air-bone gap and the type of tympanogram in predicting a middle ear effusion were also examined. The audiograms of 37 ears showed a Carhart notch; of these, 36 ears were noted to have glue ear. The correlation between the presence of a Carhart notch in the preoperative audiogram and the presence of glue at myringotomy was found to be significant (P < 0.001) (chi-square test). Using the decision rule that the presence of a Carhart notch predicts the presence of glue, the following operating characteristics were determined: correct, 83 ears (87.4%); false positive, one ear (1.1%); false negative, 11 ears (11.6%). The presence of a Carhart notch was found to be a strong predictor of the presence of glue at myringotomy.     

Is contralateral exploration necessary in girls with unilateral inguinal hernia?

Background/Purpose: Routine contralateral groin exploration in girls with unilateral inguinal hernia (UIH) continues to be controversial. The aim of this study was to determine the incidence of contralateral hernia development in girls after UIH repair. Methods: Between 1972 and 2000, 391 girls underwent repair of UIH. Ninety-one (23%) of the 391 girls underwent routine contralateral exploration during UIH repair and were excluded from the study. The median age at operation in the remaining 300 girls was 3.3 years (range, 1 month to 14 years). Two hundred ten (70%) girls had right-sided and 90 (30%) had left-sided UIH. Familial history of hernia was identified in 8 (3%) patients. The follow-up ranged from 1.5 to 14 years. Mann-Whitney U test was used for intergroup comparison. Results: A contralateral hernia developed in 24 (8%) of the 300 patients who had unilateral repair of inguinal hernia. Median time from operation to occurrence of the contralateral hernia was 3 years (range, 1 to 4 years). Age at operation, side of hernia, and familial history did not influence the development of contralateral hernia. Conclusions: These data suggest that the low incidence of contralateral hernia development in girls undergoing UIH repair does not justify routine contralateral groin exploration. J Pediatr Surg 38:756-757. [copy ] 2003 Elsevier Inc. All rights reserved.     

Combination of thiol antioxidant Silibinin with Brostallicin is associated with increase in the anti-apoptotic protein Bcl-2 and decrease in caspase 3 activity

The cytotoxic activity of Brostallicin was previously shown to be enhanced in the presence of high glutathione and glutathione transferase levels. We hypothesized that thiol antioxidants, N-acetylcysteine and Silibinin, could potentiate Brostallicin's cytotoxicity in a similar way. HepG2 and CNE-2 cells were treated with N-acetylcysteine, Silibinin and Brostallicin, either alone or in combination. Surprisingly, we found that NAC and Silibinin had adverse effects on Brostallicin's cytotoxicity. The mechanism underlying the interaction involved the apoptotic pathway as we demonstrated an increase in Bcl-2 protein levels and decrease in caspase 3 activity with the Silibinin-Brostallicin combination.