A familial frontotemporal dementia associated with C9orf72 repeat expansion and dysplastic gangliocytoma

A hexanucleotide repeat expansion in the chromosome 9 open reading frame 72 gene (C9orf72) was recently identified as the most common genetic cause of frontotemporal dementia/amyotrophic lateral sclerosis. Here we describe the clinical, pathologic, and genetic features of a Finnish C9orf72 expansion carrier, who developed a dysplastic gangliocytoma (Lhermitte-Duclos disease), a rare hamartoma/overgrowth syndrome of cerebellar granule cells associated with mutations in the phosphatase and tensin homolog gene. In addition to the dysplastic gangliocytoma, the patient showed typical transactive response DNA-binding protein with M_r 43 kD (TDP-43) pathology mainly in the cortex and the substantia nigra and numerous p62-positive/TDP-43-negative inclusions in the cerebellar granule cells. His sister carried the same gene defect and showed a similar type of TDP-43/p62 pathology in her brain. Our findings confirm that the clinical and pathologic picture of C9orf72 mutation carriers is more heterogeneous than originally thought and warrants further studies on the possible involvement of phosphatase and tensin homolog gene pathway in the specific cerebellar granule cell pathology associated with C9orf72 expansion.     

Smoking as an independent risk factor for severe skin reactions due to adjuvant radiotherapy for breast cancer

Risk factors for severe acute radiation skin reactions (ARSR) have been described with conflicting results. The aim of this study was to identify risk factors for the development of severe ARSR in women undergoing adjuvant radiotherapy (RT) for breast cancer.390 women were assessed at the first and final RT sessions and at followup. ARSR were measured by the Radiation Therapy Oncology Group/The Organization for Research and Treatment of Cancer, Acute Radiation Morbidity Scoring Criteria (RTOG/EORTC scale). Patients reported symptoms using visual analogue scale (VAS). Health related quality of life was assessed by EORTC QLQ-C30 and sleep disturbances by the MOS-Sleep questionnaire. Clinical data included smoking status (carbon monoxide in expired air), body mass index (BMI) and treatment data.RT dose, ≥50 Gy (mean difference 1.9 CI: 1.0 to 3.5, p = 0.040), high BMI (mean difference 4.3 CI: 2.2 to 8.3, p < 0.001) and smoking (mean difference 2.5 CI. 1.1 to 5.7, p = 0.027) were the factors strongest related to severe ARSR. Patients' with severe ARSR reported higher levels of pain and increased sleeping problems.To stop smoking during RT is the best decision patients can make to reduce the risk for severe ARSR since smoking is an independent risk factor.     

Symptom reporting during voluntary hyperventilation and mental load: Implications for diagnosing hyperventilation syndrome

Hyperventilation is considered an important factor in the production of a variety of somatic symptoms. This complex of symptoms is called the Hyperventilation Syndrome (HVS). Recognition of symptoms during the hyperventilation provocation test (HVPT) is a widely used criterion for diagnosing HVS. The validity of this criterion is tested in the present study.

Twenty-three patients suspected of HVS performed a HVPT (hyperventilation during 3 min) and a mental load task (Stroop Color Word Test; CWT). It appeared that about the same number of patients (61%) recognized symptoms during the HVPT as during the CWT (52%), despite severe hypocapnia in the first test and normocapnia in the second. Reporting of symptoms was significantly related to psychological state and trait measures (SCL-90 and STAI scores) and unrelated to the degree of hypocapnia. These data have far reaching consequences, as they not only undermine the validity of the HVPT, but also question the tenability of the concept of HVS.     

Towards quantifying the aesthetic outcomes of breast cancer treatment: comparison of clinical photography and colorimetry

Rationale, aims and objectives Scarring is a significant cause of dissatisfaction for women who undergo breast surgery. Scar tissue may be clinically distinguished from normal skin by aberrant colour, rough surface texture, increased thickness (hypertrophy) and firmness. Colorimeters or spectrophotometers can be used to quantitatively assess scar colour, but they require direct patient interaction and can cost thousands of dollars. By comparison, digital photography is already in widespread use to document clinical outcomes and requires less patient interaction. Thus, assessment of scar coloration by digital photography is an attractive alternative. The goal of this study was to compare colour measurements obtained by digital photography and colorimetry. Methods Agreements between photographic and colorimetric measurements of colour were evaluated. Experimental conditions were controlled by performing measurements on artificial scars created by a make‐up artist. The colorimetric measurements of the artificial scars were compared with those reported in the literature for real scars in order to confirm the validity of this approach. We assessed the agreement between the colorimetric and photographic measurements of colour using a hypothesis test for equivalence, the intraclass correlation coefficient and the Bland–Altman method. Results Overall, good agreement was obtained for three parameters (L*a*b*) measured by colorimetry and photography from the results of three statistical analyses. Conclusion Colour measurements obtained by digital photography were equivalent to those obtained using colorimetry. Thus, digital photography is a reliable, cost‐effective measurement method of skin colour and should be further investigated for quantitative analysis of surgical outcomes.     

Sexological Competence of Different Rehabilitation Disciplines and Effects of a Discipline-specific Sexological Training

Dealing with sexual problems due to disease or disability is part of medical rehabilitation, but both patients and professionals experience barriers to discuss sexual issues. A brief discipline-specific sexological training for rehabilitation professionals was therefore developed and evaluated in two rehabilitation centers in The Netherlands. Among the 283 participants were physicians (42), physical therapists (38), occupational therapists (40), psychologists and social workers (26), nurses (101), and other disciplines (36). Measurements before training, after training, and at 3–4 months follow-up showed increase of self-rated sexological competence and of scores on the Knowledge, Comfort, Approach, and Attitudes towards Sexuality Scale (KCAASS) during the training that were maintained at follow-up. Disciplines differed in sexual competence before training and in increase of sexual competence after training. Implementation of the training in other rehabilitation centers is recommended.     

5alpha-reductase 2 polymorphisms as risk factors in prostate cancer

Prostate cancer is a significant cause of death in Western countries and is under the strong influence of androgens. The steroid 5alpha-reductase 2 catalyzes the metabolism of testosterone into the more potent androgen dihydrotestosterone in the prostate gland. The enzyme is a target in pharmacological treatment of benign prostatic hyperplasia using specific inhibitors such as finasteride. Makridakis et al. have characterized the V89L and A49T polymorphisms in recombinant expression systems. The L allelic variant has a lower Vmax/Km ratio than the V variant. In the A49T polymorphism, the T variant has an increased Vmax/Km ratio. We performed a population-based case-control study of the impact of the SRD5A2 V89L and A49T polymorphisms on the risk of prostate cancer. We also studied the relation between the genotypes and age at diagnosis, tumor, node, metastasis stage, differentiation grade, prostate specific antigen and heredity. The study included 175 prostate cancer patients and 159 healthy controls that were matched for age. There was an association with SRD5A2 V89L LL genotype and metastases at the time of diagnosis, OR 5.67 (95% CI 1.44-22.30) when adjusted for age, differentiation grade, T-stage and prostate specific antigen. Heterozygous prostate cancer cases that carried the SRD5A2 A49T AT genotype were significantly younger than cases that carried the AA genotype, (mean age 66 years vs 71, P = 0.038). The SRD5A2 V89L and A49T polymorphisms were, however, not associated with altered prostate cancer risk. Further studies of the V89L polymorphism may lead to better understanding of the etiology of prostate cancer metastases.