Ecological validity of walking speed assessment after traumatic brain injury: a pilot study

OBJECTIVE: To assess the ecological validity of walking speed measurement after traumatic brain injury (TBI). PARTICIPANTS: Ten people with TBI who could walk independently and were participating in a rehabilitation program. DESIGN: Walking speed on 3 clinical gait tests (comfortable and fast pace over a 10-m distance and a 6-minute walk test) in 3 "natural" environments (a corridor in a brain injury rehabilitation unit, a car park of a metropolitan shopping center, and inside a metropolitan shopping center). Normative data were collected for 275 able-bodied pedestrians as they walked in the 3 natural environments. RESULTS: For subjects with TBI, agreement between the speeds used in the clinical gait tests and the natural environments was poor (intraclass correlation coefficient [ICC] values ranged from -0.24 to 0.63). The closest speed match was the comfortable paced 10-m walk test and walking in a corridor of a brain injury rehabilitation unit (ICC 0.63). Able-bodied pedestrians walked at significantly faster speeds than did subjects with TBI in all 3 natural environments. CONCLUSIONS: Comfortable walking speed appears to have the highest ecological validity of the clinical gait tests investigated. Practice in natural and more complex environments should be incorporated into walking rehabilitation programs for people with TBI.     

A novel in vivo procedure for volumetric flow measurements

We report on a novel procedure for invasive volumetric blood flow measurements using a commercially available Doppler flow wire system, which could, until now, only measure flow velocity. We here describe a method applicable in vivo to generate both velocity and cross-sectional area information from the same pulsed-wave Doppler signal for volumetric flow assessment. We demonstrate its feasibility and validation in vivo in pig coronary arteries. Our Doppler-derived volumetric flow measurements were compared with the respective transit-time flow and showed an excellent correlation (r = 0.969; p < 0.0001). Agreement between transit-time and Doppler-derived flow measurements could be observed for flow conditions ranging from 30 to 180 mL/min. The mean values for the two methods were 71.4 +/- 43.7 mL/min and 71.3 +/- 42.2 mL/min, respectively. We conclude that this technique might possibly be introduced into future clinical practice as an invasive procedure of choice for the assessment of volumetric blood flow.     

Very slight chance of other metastases in axillary nodes of breast cancer patients with a small sentinel node metastasis without extranodal tumor growth

OBJECTIVE: To determine in patients with mammary carcinoma and a sentinel node metastasis whether pathological parameters of the sentinel node metastasis and the primary tumour might have predictive value with respect to the presence of metastases in other axillary nodes. DESIGN: Prospective. METHOD: The study group consisted of the first 100 consecutive patients with a sentinel node metastasis, who subsequently underwent a complete axillary dissection. The patients with metastases in the non-sentinel nodes were compared to those without such metastases regarding the size of the largest sentinel node metastasis and the presence of extranodal tissue invasion near any such node, and size, and type of the primary tumour. RESULTS: The median size of the metastases in the sentinel lymph node in the two groups was 3 mm versus 13 mm respectively (p < 0.001) and the frequency of extranodal tissue invasion 3% versus 74% respectively (p < 0.001); the combination of these factors strongly predicted the presence of non-sentinel lymph node metastases in the axilla (94% area under the receiver operating characteristics curve). None of the 30 patients with a micrometastasis < or = 2.0 mm in the sentinel lymph node had metastases in the non-sentinel axillary lymph nodes. Metastases were present in the non-sentinel axillary lymph nodes in 29 of the 31 patients with extranodal tissue invasion near the sentinel node. CONCLUSION: In breast cancer patients with a sentinel lymph node metastasis < or = 2.0 mm and without extranodal tumour growth a complete axillary lymph node dissection might be unnecessary as the risk of additional metastases was very small.     

Array comparative genomic hybridization analysis of genomic alterations in breast cancer subtypes

In this study, we performed high-resolution array comparative genomic hybridization with an array of 4153 bacterial artificial chromosome clones to assess copy number changes in 44 archival breast cancers. The tumors were flow sorted to exclude non-tumor DNA and increase our ability to detect gene copy number changes. In these tumors, losses were more frequent than gains, and gains in 1q and loss in 16q were the most frequent alterations. We compared gene copy number changes in the tumors based on histologic subtype and estrogen receptor (ER) status, i.e., ER-negative infiltrating ductal carcinoma, ER-positive infiltrating ductal carcinoma, and ER-positive infiltrating lobular carcinoma. We observed a consistent association between loss in regions of 5q and ER-negative infiltrating ductal carcinoma, as well as more frequent loss in 4p16, 8p23, 8p21, 10q25, and 17p11.2 in ER-negative infiltrating ductal carcinoma compared with ER-positive infiltrating ductal carcinoma (adjusted P values < or = 0.05). We also observed high-level amplifications in ER-negative infiltrating ductal carcinoma in regions of 8q24 and 17q12 encompassing the c-myc and c-erbB-2 genes and apparent homozygous deletions in 3p21, 5q33, 8p23, 8p21, 9q34, 16q24, and 19q13. ER-positive infiltrating ductal carcinoma showed a higher frequency of gain in 16p13 and loss in 16q21 than ER-negative infiltrating ductal carcinoma. Correlation analysis highlighted regions of change commonly seen together in ER-negative infiltrating ductal carcinoma. ER-positive infiltrating lobular carcinoma differed from ER-positive infiltrating ductal carcinoma in the frequency of gain in 1q and loss in 11q and showed high-level amplifications in 1q32, 8p23, 11q13, and 11q14. These results indicate that array comparative genomic hybridization can identify significant differences in the genomic alterations between subtypes of breast cancer.     

Toxic proteins released from mitochondria in cell death

A plethora of apoptotic stimuli converge on the mitochondria and affect their membrane integrity. As a consequence, multiple death-promoting factors residing in the mitochondrial intermembrane space are liberated in the cytosol. Pro- and antiapoptotic Bcl-2 family proteins control the release of these mitochondrial proteins by inducing or preventing permeabilization of the outer mitochondrial membrane. Once released into the cytosol, these mitochondrial proteins activate both caspase-dependent and -independent cell death pathways. Cytochrome c was the first protein shown to be released from the mitochondria into the cytosol, where it induces apoptosome formation. Other released mitochondrial proteins include apoptosis-inducing factor (AIF) and endonuclease G, both of which contribute to apoptotic nuclear DNA damage in a caspase-independent way. Other examples are Smac/DIABLO (second mitochondria-derived activator of caspase/direct IAP-binding protein with low PI) and the serine protease HtrA2/OMI (high-temperature requirement protein A2), which both promote caspase activation and instigate caspase-independent cytotoxicity. The precise mode of action and importance of cytochrome c in apoptosis in mammalian cells has become clear through biochemical, structural and genetic studies. More recently identified factors, for example HtrA2/OMI and Smac/DIABLO, are still being studied intensively in order to delineate their functions in apoptosis. A better understanding of these functions may help to develop new strategies to treat cancer.     

Genome-wide scan of reading ability in affected sibling pairs with attention-deficit/hyperactivity disorder: unique and shared genetic effects

Attention-deficit/hyperactivity disorder (ADHD) and reading disability (RD) are common highly heritable disorders of childhood, which frequently co-occur. Data from twin and family studies suggest that this overlap is, in part, due to shared genetic underpinnings. Here, we report the first genome-wide linkage analysis of measures of reading ability in children with ADHD, using a sample of 233 affected sibling pairs who previously participated in a genome-wide scan for susceptibility loci in ADHD. Quantitative trait locus (QTL) analysis of a composite reading factor defined from three highly correlated reading measures identified suggestive linkage (multipoint maximum lod score, MLS>2.2) in four chromosomal regions. Two regions (16p, 17q) overlap those implicated by our previous genome-wide scan for ADHD in the same sample: one region (2p) provides replication for an RD susceptibility locus, and one region (10q) falls approximately 35 cM from a modestly highlighted region in an independent genome-wide scan of siblings with ADHD. Investigation of an individual reading measure of Reading Recognition supported linkage to putative RD susceptibility regions on chromosome 8p (MLS=2.4) and 15q (MLS=1.38). Thus, the data support the existence of genetic factors that have pleiotropic effects on ADHD and reading ability--as suggested by shared linkages on 16p, 17q and possibly 10q--but also those that appear to be unique to reading--as indicated by linkages on 2p, 8p and 15q that coincide with those previously found in studies of RD. Our study also suggests that reading measures may represent useful phenotypes in ADHD research. The eventual identification of genes underlying these unique and shared linkages may increase our understanding of ADHD, RD and the relationship between the two.     

Depression in France and Brazil: factorial structure of the 17-item Hamilton Depression Scale in inpatients

Among various research strategies for depression, the cross-cultural approach is a useful tool to investigate depressive disorders. The Hamilton Rating Scale for Depression was applied to 130 depressed inpatients in France and Brazil. Items were factorized by principal component analysis with Varimax rotation using the Kaiser or simulation method for factor sorting. Three factors were obtained in France, and four in Brazil. The first factor includes the core symptoms of depression in both samples. Qualitative and quantitative differences appeared in the anxiety factor between Brazilian and French samples. Insomnia items appeared as another factor for both groups. A limitation of this study is that it was conducted with small inpatient samples. Principal component analysis of the Hamilton Rating Scale for Depression for depressive inpatients in these two countries showed a similar structure. Differences observed were in the way anxiety items were distributed.     

Alveolar rhabdomyosarcoma of the cervix

BACKGROUND: Alveolar rhabdomyosarcoma (RMS) has a high risk for local and distal failure. Multimodal management of a patient with alveolar RMS of the cervix uteri is outlined. CASE: A 39-year-old woman suffered from alveolar RMS of the cervix without involvement of uterus and parametrium. She was treated with total hysterectomy and left salpingo-oophorectomy. Systemic chemotherapy and pelvic irradiation were also offered. She remains in clinical remission 3 years after presentation. CONCLUSION: Postoperative chemotherapy and irradiation could be effective treatments for alveolar rhabdomyosarcoma of the cervix in adult patients.