Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic renal cell carcinoma

OBJECTIVES

To analyse the implications of DNA mismatch repair genes hMLH1 and hMSH2 in sporadic renal cell carcinoma (RCC).

MATERIALS AND METHODS

Specimens of tumour and healthy renal tissue were collected from 89 patients treated for sporadic RCC. Another 95 blood samples taken from individuals with no history of cancer were also analysed. After DNA extraction and PCR amplification, microsatellite instability (MSI) was determined using the Bethesda microsatellite panel, two exonic microsatellites of the TGFbRII and BAX genes, and the microsatellite D3S1611. The promoter methylation status of hMLH1 was investigated using the HpaII and MspI restriction enzymes. In addition, a sequencing analysis of complete coding region of hMLH1 and hMSH2 genes was performed.

RESULTS

MSI and promoter hypermethylation of hMLH1 were not detected. Interestingly, loss of heterozygosity (LOH) was common among patients with RCC, particularly in microsatellite D3S1611 (34.9%). Mutations were identified in eight patients: K618A and V716M in gene hMLH1; and I145V, G322D, and the novel mutation P349A, in gene hMSH2. The mutations also appeared in healthy renal tissue and therefore, were considered as germline DNA sequence variations. There were G322D and K618A changes in >1% of the healthy control subjects, suggesting that they are DNA polymorphisms.

CONCLUSIONS

Our data show that loss of function of both hMLH1 and hMSH2 is not involved in sporadic RCC, either by promoter methylation or mutation in their exons. However, LOH indicated that chromosomal instability affecting large fragments of DNA was the main genetic alteration we detected associated with RCC.     

Lack of influence of COMT Val158Met genotype on cognition in first-episode non-affective psychosis

COMT gene is a logical candidate gene for schizophrenia. Moreover, variations in the COMT Val158Met functional polymorphism have been associated with prefrontal cognitive abnormalities among patients with schizophrenia, healthy relatives and controls. In this study, using an epidemiologically-based sample of 130 patients experiencing a first-episode of a non-affective psychosis, we examined whether COMT Val158Met genotype influenced cognitive performance on the phenotypic expression of psychosis. We found no significant differences in any cognitive measure according to COMT genotype. These findings, together with previously published research, put the relationship between COMT genotype and cognitive performance in doubt.     

Impact of attention-deficit/hyperactivity disorder on the patient and family: results from a European survey

Background

Children with attention-deficit/hyperactivity disorder (ADHD) often experience problems with education, interaction with others and emotional disturbances. Families of ADHD children also suffer a significant burden, in terms of strain on relationships and reduced work productivity. This parent survey assessed daily life for children with ADHD and their families.

Method

This pan-European survey involved the completion of an on-line questionnaire by parents of children (6–18 years) with ADHD (ADHD sample) and without ADHD (normative population sample). Parents were questioned about the impact of their child's ADHD on everyday activities, general behaviour and family relationships.

Results

The ADHD sample comprised 910 parents and the normative population sample 995 parents. 62% of ADHD children were not currently receiving medication; 15% were receiving 6–8 hour stimulant medication and 23% 12-hour stimulant medication. Compared with the normative population sample, parents reported that ADHD children consistently displayed more demanding, noisy, disruptive, disorganised and impulsive behaviour. Significantly more parents reported that ADHD children experienced challenges throughout the day, from morning until bedtime, compared with the normative population sample. Parents reported that children with ADHD receiving 12-hour stimulant medication experienced fewer challenges during early afternoon and late afternoon/early evening than children receiving 6–8 hour stimulant medication; by late evening and bedtime however, this difference was not apparent. ADHD was reported to impact most significantly on activities such as homework, family routines and playing with other children. All relationships between ADHD children and others were also negatively affected, especially those between parent and child (72% of respondents). Parents reported that more children with ADHD experienced a personal injury in the preceding 12 months, including those requiring the attention of healthcare professionals. Although 68% of parents were satisfied with their child's current treatment, 35–40% stated that their child's ADHD symptoms needed to be more effectively treated during the afternoon and evening.

Conclusion

This parent survey highlights the breadth of problems experienced by ADHD children and the impact throughout the day on both activities and relationships. Therefore, there is a need for treatment approaches that take into account the 24-hour impact of the disorder and include all-day coverage with effective medication.     

Retroperitoneal leiomyosarcoma of the inferior vena cava mimicking a liver tumor

Leiomyosarcoma of the inferior vena cava (IVC) is a rare sarcoma, but it is the most common primary malignancy of the IVC. It has an extremely poor prognosis. We describe a 60-year-old white female complaining of abdominal fullness for 7 weeks before she sought medical assistance. Initial work-up including sonography, computed tomography, and magnetic resonance showed a tumor in the right upper quadrant of the abdominal cavity originating from the liver with compression of the IVC and displacement of the right kidney. The patient underwent surgical resection of the tumor with clear margins and reconstruction of the IVC using a Dacron tubular graft. Postoperatively, she was placed on Coumadin and adjuvant chemotherapy was started. Subsequently, the patient developed metastasis into the liver and peripancreatic nodes during the follow-up period. Considering the aggressiveness of this tumor, early radical en block resection with clear margins is still the only chance for long-term survival.     

Endovascular repair of an ascending aortic pseudoaneurysm with a septal occluder device: mid-term follow-up

Ascending pseudoaneurysm is an infrequent complication of ascending aortic surgery. Redo operations are often associated with a high surgical morbidity and mortality. Endovascular management of ascending aortic pathologies with endoluminal graft therapies are challenging due to short landing zones and the fear of flow obstruction to the coronaries and brachiocephalic circulation. We report mid-term follow-up of the management of an ascending aortic pseudoaneurysm using a an Amplatz septal occluder (AGA Medical Corp, Golden Valley, MN) in a 51-year-old man considered at high risk for conventional open surgical repair.