The assessment of values in laryngeal cancer: reliability of measurement methods

Although quantitative estimates of patients' attitudes toward the relative importance of different aspects of health are of great potential usefulness in medical decision making, there is little information about the stability of such values over time, particularly in patients whose clinical state is changing. To examine these questions, we selected a group of patients with laryngeal cancer undergoing treatment with radiotherapy. In this group of patients clinical problems are relatively circumscribed and related to the voice, and a temporary deterioration in voice-related symptoms and abilities is expected during treatment. Thirty patients were interviewed at the start and completion of a month's course of treatment. At each interview patients rated the quality of their own voices using a number of visual analogue scales and also provided both holistic and decomposed quantitative values for the importance of different aspects of voice function and sound. Although the analogue scales demonstrated the anticipated deterioration in the quality of the patients' voices, these changes in clinical state were not accompanied by any changes in the values the patients assigned to each aspect of voice sound and function. These results indicate that at least in the short term the values expressed by patients appear to be stable and uninfluenced by changes in their own clinical state. Longer term studies involving more systemic illnesses should now be carried out.     

Radiographic damage associated with low bone mineral density and vertebral deformities in rheumatoid arthritis: The Oslo‐Truro‐Amsterdam (OSTRA) collaborative study

Objective

To examine variables associated with bone mineral density (BMD) and vertebral deformities in women with rheumatoid arthritis (RA) from 3 northwest European countries.

Methods

Female patients were recruited from rheumatology clinics in Oslo, Norway; Truro, UK; and Amsterdam, The Netherlands (150 total, 50 per center, age 50–70 years, disease duration ≥5 years). Demographic and clinical data were collected and BMD was measured by means of dual energy x‐ray absorptiometry. Associations between demographic and clinical measures on the one hand and BMD and vertebral deformities on the other were investigated by single and multiple regression analyses.

Results

Body mass index (BMI), medication use, RA damage measures, and BMD differed significantly between the 3 centers. Overall, Norwegian patients had the lowest BMI, used more corticosteroids and antiosteoporotic drugs, had lower joint damage measured by Larsen score, and lower BMD at both spine and hip. High age, low BMI, and high cumulative dose of corticosteroids (last 2 years) are related to low BMD. A high Larsen score was associated with low BMD at the hip. Larsen score was the independent determinant of vertebral deformities after correction for center, age, BMI, and BMD.

Conclusion

Data from 3 countries on BMD and vertebral deformities in female patients aged 50–70 years with longstanding RA are presented, demonstrating an association between radiographic RA damage and low BMD and between radiographic RA damage and vertebral deformities.

     

Recurrent deletion of 3p13 targets multiple tumour suppressor genes and defines a distinct subgroup of aggressive ERG fusion‐positive prostate cancers

Deletion of 3p13 has been reported from about 20% of prostate cancers. The clinical significance of this alteration and the tumour suppressor gene(s) driving the deletion remain to be identified. We have mapped the 3p13 deletion locus using SNP array analysis and performed fluorescence in situ hybridization (FISH) analysis to search for associations between 3p13 deletion, prostate cancer phenotype and patient prognosis in a tissue microarray containing more than 3200 prostate cancers. SNP array analysis of 72 prostate cancers revealed a small deletion at 3p13 in 14 (19%) of the tumours, including the putative tumour suppressors FOXP1, RYBP and SHQ1. FISH analysis using FOXP1‐specific probes revealed deletions in 16.5% and translocations in 1.2% of 1828 interpretable cancers. 3p13 deletions were linked to adverse features of prostate cancer, including advanced stage (p < 0.0001), high Gleason grade (p = 0.0125), and early PSA recurrence (p = 0.0015). In addition, 3p13 deletions were linked to ERG⁺ cancers and to PTEN deletions (p < 0.0001 each). A subset analysis of ERG⁺ tumours revealed that 3p13 deletions occurred independently from PTEN deletions (p = 0.3126), identifying tumours with 3p13 deletion as a distinct molecular subset of ERG⁺ cancers. mRNA expression analysis confirmed that all 3p13 genes were down regulated by the deletion. Ectopic over‐expression of FOXP1, RYBP and SHQ1 resulted in decreased colony‐formation capabilities, corroborating a tumour suppressor function for all three genes. In summary, our data show that deletion of 3p13 defines a distinct and aggressive molecular subset of ERG⁺ prostate cancers, which is possibly driven by inactivation of multiple tumour suppressors. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

The diagnosis and management of allergic reactions in patients sensitized to non-specific lipid transfer proteins

Sensitization to one or more non-specific lipid transfer proteins (nsLTPs), initially thought to exist mainly in southern Europe, is becoming accepted as a cause of allergic reactions to plant foods across Europe and beyond. The peach nsLTP allergen Pru p 3 is a dominant sensitizing allergen and peaches a common food trigger, although multiple foods can be involved. A frequent feature of reactions is the requirement for a cofactor (exercise, alcohol, non-steroidal anti-inflammatory drugs, Cannabis sativa) to be present for a food to elicit a reaction. The variability in the food and cofactor triggers makes it essential to include an allergy-focused diet and clinical history in the diagnostic workup. Testing on suspected food triggers should also establish whether sensitization to nsLTP is present, using purified or recombinant nsLTP allergens such as Pru p 3. The avoidance of known trigger foods and advice on cofactors is currently the main management for this condition. Studies on immunotherapy are promising, but it is unknown whether such treatments will be useful in populations where Pru p 3 is not the primary sensitizing allergen. Future research should focus on the mechanisms of cofactors, improving diagnostic accuracy and establishing the efficacy of immunotherapy.     

The Premonitory Phase of Migraine – What Can We Learn From It?

This review aims to understand the prevalence of premonitory symptoms in migraine, postulate their mechanisms, and compare these with functional imaging studies. A thorough literature review was conducted using PubMed for prevalence studies of premonitory symptoms in migraine and functional imaging studies in the premonitory phase. The majority of studies have been retrospective reporting a prevalence of 7‐88% for premonitory symptoms in migraine. Only one study has investigated premonitory symptoms prospectively and used preselected patients with recognized premonitory symptoms. The majority of patients were able to predict correctly the onset of migraine headache. Only one functional imaging study has been conducted in the premonitory phase that showed activation of posterolateral hypothalamus, midbrain tegmental area and substantia nigra, periaqueductal gray, dorsal pons, and various cortical areas including occipital, temporal, and prefrontal cortex. Subgroup analysis of patients with photophobia more than without photophobia in the premonitory phase showed activation of the occipital cortex. Comparison of patients with nausea more than without nausea in the premonitory phase showed activation in upper dorsal medulla and periaqueductal gray. Premonitory symptoms are common in migraine, although the true prevalence cannot be stated with certainty in the absence of prospective studies in unselected patients. Hypothalamic involvement can explain many of the premonitory symptoms. Activation of the the brainstem structures and hypothalamus before pain suggests a pivotal role of these structures in the pathogenesis of migraine. Hypersensitivity to light and occurrence of nausea in migraine is associated with activation of central brain structures involved in these pathways, and this can occur in the absence of pain.