Interlaboratory comparison of HER-2 oncogene amplification as detected by chromogenic and fluorescence in situ hybridization.

PURPOSE: Chromogenic in situ hybridization (CISH) is a new modification of the fluorescence in situ hybridization (FISH) technique for detection of oncogene amplification in archival tumor samples. In CISH, the oncogene probe is detected using a peroxidase reaction, allowing use of transmitted light microscopy. We compared detection of HER-2/neu amplification by CISH with a Food and Drug Administration-approved two-color FISH test in an interlaboratory setting. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded tumor samples from 197 breast cancers were analyzed for HER-2 amplification by CISH. Two-color FISH (PathVysion) CISH of 17 centromere was done if the observer considered it necessary to ascertain amplification status in tumors with borderline HER-2 CISH copy numbers. RESULTS: Paired CISH/FISH results were available from 192 (97%) of 197 cases, no clear difference in success rates of either method was observed. Centromere 17 CISH was considered necessary in seven tumors. CISH and two-color FISH results were concordant in 180 cases (93.8%). There were 92 and 88 tumors found HER-2 amplified and nonamplified, respectively, by both methods. Eight tumors were amplified by CISH but not by FISH, and four tumors exhibited the opposite condition (kappa coefficient 0.875). In 7 of 12 cases differences between the two methods could have related to a lack of CISH chromosome 17 information. The remaining cases were explained by difficult histology (ductal carcinoma in situ, poor representativity, dense lymphocytic infiltration, or intratumoral heterogeneity). CONCLUSIONS: These results indicate that CISH could provide an accurate and practical alternative to FISH for clinical diagnosis of HER-2/neu oncogene amplification in archival formalin-fixed breast cancer samples.     

Can virtual simulation of breast tangential portals accurately predict lung and heart volumes?

A treatment portal or simulator image has traditionally been used to demonstrate the lung and heart coverage of the breast tangential portal. In many cases, these images were acquired as a planning session on the linear accelerator. The patients were also CT scanned to assess the lung/heart volume and to determine the surgical site depth for the electron‐boost energy. A study using 50 consecutive patients was performed comparing the digitally reconstructed radiograph (DRR) from the virtual simulation with treatment portal images. Modification to the patient's arm position is required when performing the planning CT scans due to the aperture size of the CT scanner. Virtual simulation was used to assess the potential variation of lung and heart measurements. The average difference in lung volume between the DRR and portal image was less than 2 mm, with a range of 0?5 mm. Arm position did not have a sig­nificant impact on field deviation; however, great care was taken to minimize any changes in arm position. The modification of the arm position for CT scanning did not lead to significant variations between the DRRs and portal images. The Advantage Sim software has proven capable of producing good quality DRR images, providing a realistic representation of the lung and heart volume included in the treatment portal.     

Auditing paediatric diabetes care and the impact of a specialist nurse trained in paediatric diabetes

AIMS: To define outcome measures for auditing the clinical care of children and adolescents with insulin dependent diabetes mellitus (IDDM) and to assess the benefit of appointing a dedicated paediatric trained diabetes specialist nurse (PDSN). METHODS: Retrospective analysis of medical notes and hospital records. Glycaemic control, growth, weight gain, microvascular complications, school absence, and the proportion of children undergoing an annual clinical review and diabetes education session were assessed. The effect of the appointment of a PDSN on the frequency of hospital admission, length of inpatient stay, and outpatient attendance was evaluated. RESULTS: Children with IDDM were of normal height and grew well for three years after diagnosis, but grew suboptimally thereafter. Weight gain was above average every year after diagnosis. Glycaemic control was poor at all ages with only 16% of children having an acceptable glycated haemoglobin. Eighty five per cent of patients underwent a formal annual clinical review, of whom 16% had background retinopathy and 20% microalbuminuria in one or more samples. After appointing the PDSN the median length of hospital stay for newly diagnosed patients decreased from five days to one day, with 10 of 24 children not admitted. None of the latter was admitted during the next year. There was no evidence of the PDSN affecting the frequency of readmission or length of stay of children with established IDDM. Non-attendance at the outpatient clinic was reduced from a median of 19 to 10%. CONCLUSIONS: Outcome measures for evaluating the care of children with IDDM can be defined and evaluated. Specialist nursing support markedly reduces the length of hospital stay of newly diagnosed patients without sacrificing the quality of care.     

Inflammatory bowel disease and predisposition to osteopenia

The prevalence of osteopenia in children with inflammatory bowel disease (IBD) is unknown. The effect of nutritional state, disease activity, and steroid therapy on bone mineral content (BMC) of whole body, lumbar spine, and left femoral neck measured by dual energy x ray absorptiometry in 32 children with IBD was assessed by comparison with 58 healthy local school children. Using the control data, a predicted BMC was calculated taking into account bone area, age, height, weight, and pubertal stage. The measured BMC in children with IBD was expressed as a percentage of this predicted value (% BMC). Mean (SD) % BMC was significantly reduced for the whole body and left femoral neck in the children with IBD (97.0 (4.5)% and 93.1 (12.0)% respectively, p < 0.05). Of the children with IBD, 41% had a % BMC less than 1 SD below the mean for the whole body and 47% at the femoral neck. Reduction in % BMC was associated with steroid usage but not with the magnitude of steroid dose, disease activity, or biochemical markers of bone metabolism. In conclusion, osteopenia is relatively common in childhood IBD and may be partly related to the previous use of steroids.     

Tuberous sclerosis complex and Wolff-Parkinson-White syndrome

This report highlights the association between tuberous sclerosis and Wolff-Parkinson-White syndrome. Ten patients with concurrent diagnoses of Wolff-Parkinson-White syndrome and tuberous sclerosis were identified. Wolff-Parkinson-White syndrome presented early in life, nine cases being diagnosed in the first year. Eight of the 10 cases were male. In eight cases, the syndrome was associated with supraventricular tachycardias, and in nine with cardiac rhabdomyomata. One child died from cardiac failure secondary to obstruction of the left ventricular outflow tract by a rhabdomyoma. Five of nine survivors showed resolution of Wolff-Parkinson-White syndrome on follow up. The accessory pathway was localised in nine patients from surface electrocardiograms: six children had left sided pathways and three had right sided pathways.     

Epidemiology of cerebral palsy in England and Scotland, 1984-9

AIMS—To report on the epidemiology of cerebral palsy in England and Scotland, to provide information on the prevalence of cerebral palsy and the severity of the disability or any co-morbidity.METHODS—Cerebral palsy registers were compiled from multiple sources of ascertainment covering all of Scotland and the counties of Merseyside, Cheshire, Berkshire, Buckinghamshire, Northamptonshire and Oxfordshire in England. All cases of cerebral palsy born in 1984 to 1989, to mothers resident in the area, were included. Denominator number of live births and neonatal deaths for determining birthweight specific prevalence were obtained from birth and death registrations. Learning, manual, and ambulatory disabilities were graded for severity. Any co-existing sensory (hearing or visual) morbidity was also graded for severity.RESULTS—There were 789 411 live births in 1984-9, with 3651 neonatal deaths (neonatal mortality 4.6 per 1000 live births) and 1649cases of cerebral palsy—a cerebral palsy prevalence of 2.1 per 1000 neonatal survivors. The birthweight specific cerebral palsy prevalence ranged from 1.1 per 1000 neonatal survivors in infants weighing ?2500 g to 78.1 in infants weighing <1000 g. There was no significant time trend in prevalence of cerebral palsy in any of the birthweight groups, in contrast to the fall in neonatal mortality observed in all birthweight groups. Of the 1649 cases of cerebral palsy, 550 (33.4%) had severe ambulatory disability (no independent walking), 390 (23.7%) had severe manual disability (incapable of feeding or dressing unaided), 381 (23.1%) had severe learning disability (IQ <50), 146 (8.9%) had severe visual disability (vision <6/60 in the better eye) and 12 had severe hearing disability (>70 dB loss).CONCLUSIONS—Registers fill an important gap left by the lack of routine data on the prevalence of disability in children. The ability to record trends in the prevalence and the severity of the disability should inform those who have responsibility for providing services for children with disabilities.     

Causes of re-recurrence after polytetrafluoroethylene patch saphenoplasty for recurrent varicose veins

BACKGROUND: The aim of this study was to determine whether a polytetrafluoroethylene (PTFE) patch sutured over the religated saphenofemoral junction could reduce the rate of recurrence after operation for recurrent varicose veins. METHODS: Fifty patients who had surgery for recurrent long saphenous incompetence (81 legs had a small PTFE patch sutured over the religated saphenofemoral junction. There were no major complications following surgery. Three patients had a wound infection or delayed healing. All patients were invited for clinical examination and duplex imaging at a median of 19 (range 6-39) months after operation. RESULTS: Some 38 of 43 patients (70 legs) remained satisfied with the results of surgery; 16 (23 per cent) of 70 legs had visible veins on inspection and eight of these (11 per cent) involved symptomatic recurrence. Duplex imaging showed that recurrence was due to saphenofemoral junction incompetence in ten legs; two appeared to have a major groin connection but the other eight appeared to have neovascularization. Other causes were thigh perforator reflux (three legs) and cross-groin collaterals (three). Eleven of the 16 legs with recurrence had varicography but in two the procedure was a technical failure. Two legs had evidence of a significant connection (more than 3 mm) and two a minor connection (less than 3 mm) to the femoral vein at the level of the PTFE patch, but in the remainder recurrence was due to upper thigh perforating veins. There was good concordance between duplex imaging and varicography. CONCLUSION: PTFE patch saphenoplasty appears to be safe. Although these are early results, the technique seems potentially as effective as other barrier methods that have been investigated; in ten legs (12 per cent) recurrence was attributed to failure at the level of the PTFE patch.     

The art-gallery as a resource for recovery for people who have experienced psychosis

Dominant personal and community narratives of psychosis can often be experienced as oppressive and stigmatising. An important aspect of recovery may be overcoming this internalised, self-depreciating story. This intervention sought to understand whether an art gallery-based group facilitated modification of the dominant narrative of psychosis in the participants’ personal narratives, promoted recovery, wellbeing, and a subjective sense of social inclusion. The narratives of mental health and gallery staff were included to investigate the modification of the dominant narrative in their personal narratives. People with an experience of psychosis participated in a gallery-based group where they reflected on paintings related to their life experiences. Participant interviews at the conclusion of the group were subjected to literary and social context narrative analysis. The findings suggested that some individuals used art-related concepts to modify the dominant narrative within their personal narrative. A community narrative regarding a different staff–client relationship, characterised by validation, commonality, friendship and genuineness, emerged within the group. The intervention was depicted as promoting recovery and wellbeing, mainly through achievement, and described as more successfully addressing bonding social capital than bridging social capital. Art gallery-based interventions show some promise to provide a safe haven where people with a psychosis can engage in a recovery-oriented approach to mental health care, where a different staff–client relationship could occur, away from the demands and possible stigma of mental health services.