Are you also what your mother eats? Distinct proteomic portrait as a result of maternal high-fat diet in the cerebral cortex of the adult mouse.

Epidemiological studies suggest an association between maternal obesity and adverse neurodevelopmental outcomes in offspring. Our aim was to compare the global proteomic portrait in the cerebral cortex between mice born to mothers on a high-fat or control diet who themselves were fed a high-fat or control diet. Male mice born to dams fed a control (C) or high-fat (H) diet 4 weeks before conception and during gestation, and lactation were assigned to either C or H diet at weaning. Mice were killed at 19 weeks and their cerebral cortices were analysed using a two-dimensional liquid chromatography-mass spectrometry methodology. In total, 6 695 proteins were identified (q<0.01), 10% of which were modulated in at least one of the groups relative to controls. In silico analysis revealed that mice clustered based on the diet of the mother and not their own diet and that maternal high-fat diet was significantly associated with response to hypoxia/oxidative stress and apoptosis in the cerebral cortex of the adult offspring. Maternal high-fat diet resulted in distinct endophenotypic changes of the adult offspring cerebral cortex independent of its current diet. The identified proteins could represent novel therapeutic targets for the prevention of neuropathological features resulting from maternal obesity.

Systemic delivery of E6/7 siRNA using novel lipidic particles and its application with cisplatin in cervical cancer mouse models.

Small interfering RNA (siRNA) shows great promise in cancer therapy, but its effectiveness in vivo still remains a crucial issue for its transition into the clinics. Although the successful use of polyethylene glycol (PEG)ylated lipidic delivery systems have already been reported, most of the formulation procedures used are labour intensive and also result in unstable end products. We have previously developed a simple yet efficient hydration-of-freeze-dried-matrix (HFDM) method to entrap siRNA within lipid particles, in which the products exhibited superior stability. Here, we show that these HFDM-formulated particles are stable in the presence of serum and can deliver siRNA efficiently to tumours after intravenous administration. Using these particles, around 50% knockdown of the target gene expression was observed in tumours. With the use of siRNA targeting the E6/7 oncogenes expressed in cervical cancer, we showed a 50% reduction in tumour size. This level of tumour growth suppression was comparable to that achieved from cisplatin at the clinically used dose. Overall, our results demonstrate the feasibility of using HFDM-formulated particles to systematically administer E6/7-targeted siRNA for cervical cancer treatment. The simplicity of preparation procedure along with superior product stability obtained from our method offers an innovative approach for the in vivo delivery of siRNA.

Deep-vein thrombosis in high-energy skeletal trauma despite thromboprophylaxis.

We report the incidence and location of deep-vein thrombosis in 312 patients who had sustained high-energy, skeletal trauma. They were investigated using magnetic resonance venography and Duplex ultrasound. Despite thromboprophylaxis, 36 (11.5%) developed venous thromboembolic disease with an incidence of 10% in those with non-pelvic trauma and 12.2% in the group with pelvic trauma. Of patients who developed deep-vein thrombosis, 13 of 27 in the pelvic group (48%) and only one of nine in the non-pelvic group (11%) had a definite pelvic deep-vein thrombosis. When compared with magnetic resonance venography, ultrasound had a false-negative rate of 77% in diagnosing pelvic deep-vein thrombosis. Its value in the pelvis was limited, although it was more accurate than magnetic resonance venography in diagnosing clots in the lower limbs. Additional screening may be needed to detect pelvic deep-vein thrombosis in patients with pelvic or acetabular fractures.

Post PSRRP anorectol manometry--experience of 115 cases of imperforate anus.

The conventional treatment of high and intemiediate anomalies of anorectal malformations is proximal pelvic colostomy in neonate (day 1) followed by PSARP (postsagittal anorectoplasty) by the age of 4-6 months and closure of colostomy when adequate dilatation of neo-anus has been performed using Nol 2 or 13 Hegar's dilator or No4 St Mark's anal dilator, It is usually done 3 months after the PSARP operation (anorectal pull through), ie, around 9 months. So the child born without anus in the perineum should be able to pass stool via his or her neo-anus by the age of 9 months and they should ideally be penneally continent. The present study, between August 1993 and December 1999, on the anorectal continence evaluation by doing anorectal manometry was carried out in 115 babies who underwent PSARP operation and subsequent closure of the colostomy. The study showed intermediate anomalies dominated the picture in both males and females (103 babies belonging to intermediate anomalies and 12 babies having high anomalies). In all these children the results of continence have been studied both clinically (Kiesewetter criteria) and by anorectal manometry.

Use of the Ilizarov technique to improve limb function following hemipelvectomy.

AIMS: Limb salvage surgery combined with tumour resection has become established in the management of pelvic tumours. However, subsequent reconstructive options for maintenance of quality of life lead to varied outcomes. We present a hitherto undescribed use of the Ilizarov technique as a second stage adjunct, for the optimisation of function, after first stage tumour resection and arthrodesis. METHODS: We describe the surgical technique used to address leg length discrepancy and abductor dysfunction following internal hemipelvectomy with ischifemoral arthrodesis. Distal femoral and distal tibial lengthening using circular frames, with a valgus subtrochanteric femoral osteotomy, enabled a rapid correction of both anomalies. Controlled varus correction at the distal femoral osteotomy site was performed to obtain a horizontal joint line at the knee. CONCLUSION: The Ilizarov technique is suitable for selected patients with tumour free survival following the initial resection. Our experience indicates that it is a good alternative to a mammoth one stage internal hemipelvectomy with reconstruction. The latter is often attempted even though there is a high risk of local recurrence and distant metastasis.

Use of the Ilizarov technique to improve limb function following hemipelvectomy. A case report.

Various surgical methods have been used for reconstruction after limb salvage surgery for pelvic tumours. We present a case of use of the Ilizarov technique as a second stage adjunct, for the improvement of function, after first stage tumour resection and arthrodesis. This technique is suitable for selected patients with tumour-free survival following the initial resection. Though not described before, our experience indicates it is an alternative to a mammoth one stage internal hemipelvectomy with reconstruction, that is often attempted even though there is a high risk of local recurrence and distant metastasis.

Percutaneous pulsed lavage for the infected knee replacement.

The low incidence of infection in knee arthroplasty is in sharp contrast to the high morbidity associated with its occurrence. This lends urgency to the need for early diagnosis and prompt management when infection does appear. To add to the armamentarium of the existing modalities in dealing with this condition, a new technique is described, which allows lavage at high pressure through a minimal access approach. It has been used successfully in two cases, though the follow-up was less than two years. A long-term follow-up will allow us to judge if this technique, used for the correct indications, can promote the longevity of the prosthesis threatened by infection.

Intramedullary hip screw versus sliding hip screw for unstable intertrochanteric femoral fractures in the elderly.

We report a randomised, prospective study comparing a standard sliding hip screw and the intramedullary hip screw for the treatment of unstable intertrochanteric fractures in the elderly. One hundred and two patients were randomised on admission to two treatment groups. Fifty-two patients were treated with a compression hip screw (CHS), and fifty had intramedullary fixation with an intramedullary hip screw (IMHS). Patients were followed for 1 year and had a clinical and radiological review at 3, 6 and 12 months. The mean duration of operation and fluoroscopy screening time was significantly greater for insertion of the intramedullary hip screw. There was no difference between the groups with regard to transfusion requirements or time to mobilise after surgery. There were two technical complications in the CHS group and three in the IMHS group. There was no significant difference between the two groups in radiological or functional outcome at 12 months. It remains to be shown whether the theoretical advantages of intramedullary fixation of extracapsular hip fractures bring a significant improvement in eventual outcome.