One Week of Hospitalization Following Elective Hip Surgery Induces Substantial Muscle Atrophy in Older Patients

Objectives

Short successive periods of skeletal muscle disuse have been suggested to substantially contribute to the observed loss of skeletal muscle mass over the life span. Hospitalization of older individuals due to acute illness, injury, or major surgery generally results in a mean hospital stay of 5 to 7 days, during which the level of physical activity is strongly reduced. We hypothesized that hospitalization following elective total hip arthroplasty is accompanied by substantial leg muscle atrophy in older men and women.

Detailed gene copy number and RNA expression analysis of the 17q12-23 region in primary breast cancers

Chromosome region 17q12-23 commonly shows an increase in DNA copy number in breast cancers, suggesting that several oncogenes are located at this site. We performed a high-resolution expression array and comparative genomic hybridization analysis of genes mapped to the entire 17q12-23 region, to identify novel candidate oncogenes. We identified 24 genes that showed significant overexpression in breast cancers with gain of 17q12-23, compared to cancers without gain. These genes included previously identified oncogenes, together with several novel candidate oncogenes. FISH analysis using specific gene probes hybridized to tissue arrays confirmed the underlying amplification of overexpressed genes. This high-resolution analysis of the 17q12-23 region indicates that several established and novel candidate oncogenes, including a Wnt-signaling pathway member, are amplified and overexpressed within individual primary breast cancer samples. We were also able to confirm the presence of two apparently separate and reciprocally amplified groups of genes within this region. Investigation of these genes and their functional interactions will facilitate our understanding of breast oncogenesis and optimal management of this disease.     

Genetic Pathways of Colorectal Carcinogenesis Rarely Involve the PTEN and LKB1 Genes Outside the Inherited Hamartoma Syndromes

Germline mutations of the PTEN/MMAC1/TEP and LKB1 genes cause hamartomas to develop in the gastrointestinal tracts of patients with Cowden syndrome and Peutz-Jeghers syndrome, respectively. PTEN mutations may also be responsible for some cases of juvenile polyposis. Histologically, hamartomas appear benign, but there is good evidence that in these syndromes, the hamartomas can progress to colorectal carcinoma. It remains unknown whether or not cancers that develop from hamartomas acquire a spectrum of mutations similar to those in sporadic colon cancers. PTEN and LKB1 are candidate genes for mutations in sporadic colon cancers, either as initiating events in tumorigenesis or providing a selective advantage during tumor growth. Using single-strand conformational polymorphism analysis, we have screened a set of sporadic colon cancers for somatic mutations in PTEN and LKB1. No variants predicted to alter protein function were detected in LKB1, but 1 of 72 cancers showed a somatic mutation in PTEN, together with allele loss. This cancer did not have a detectable APC mutation or allele loss at APC. It remains possible that PTEN and LKB1 are inactivated in other sporadic colon cancers by means such as deletion or promoter methylation. Like BRCA1 and BRCA2, however, it appears that PTEN and LKB1 mutations can cause cancers when present in the germline, but occur rarely in the soma.     

GATA6 mutations: Characterization of two novel patients and a comprehensive overview of the GATA6 genotypic and phenotypic spectrum

The first human mutations in GATA6 were described in a cohort of patients with persistent truncus arteriosus, and the phenotypic spectrum has expanded since then. This study underscores the broad phenotypic spectrum by presenting two patients with de novo GATA6 mutations, both exhibiting complex cardiac defects, pancreatic, and other abnormalities. Furthermore, we provided a detailed overview of all published human genetic variation in/near GATA6 published to date and the associated phenotypes (n = 78). We conclude that the most common phenotypes associated with a mutation in GATA6 were structural cardiac and pancreatic abnormalities, with a penetrance of 87 and 60%, respectively. Other common malformations were gallbladder agenesis, congenital diaphragmatic hernia, and neurocognitive abnormalities, mostly developmental delay. Fifty‐eight percent of the mutations were de novo, and these patients more often had an anomaly of intracardiac connections, an anomaly of the great arteries, and hypothyroidism, compared with those with inherited mutations. Functional studies mostly support loss‐of‐function as the pathophysiological mechanism. In conclusion, GATA6 mutations give a wide range of phenotypic defects, most frequently malformations of the heart and pancreas. This highlights the importance of detailed clinical evaluation of identified carriers to evaluate their full phenotypic spectrum.     

Complex CGH alterations on chromosome arm 8p at candidate tumor suppressor gene loci in breast cancer cell lines

Loss of genetic material from chromosome arm 8p occurs frequently in human breast carcinomas, consistent with this region of the genome harboring one or more tumor suppressor genes (TSGs). We used the complementary techniques of microsatellite-based LOH, high-density FISH, and conventional CGH on 6 breast cancer cell lines (MCF7, SKBR3, T47D, MDA MB453, BT549, and BT474) to investigate the molecular cytogenetic changes occurring on chromosome 8 during tumorigenesis, with particular emphasis on 6 potential TSGs on 8p. We identified multiple alterations of chromosome 8, including partial or complete deletion of 8p or 8q, duplication of 8q, and isochromosome 8q. The detailed FISH analysis showed several complex rearrangements of 8p with differing breakpoints of varying proximity to the genes of interest. High rates of LOH were observed at markers adjacent to or within PCM1, DUSP4/MKP2, NKX3A, and DLC1, supporting their status as candidate TSGs. Due to the complex ploidy status of these cell lines, relative loss of 8p material detected by CGH did not always correlate with microsatellite-based LOH results. These results extend our understanding of the mechanisms accompanying the dysregulation of candidate tumor suppressor loci on chromosome arm 8p, and identify appropriate cellular systems for further investigation of their biological properties.     

TRISS unexpected survivors--a statistical phenomenon or a clinical reality?

Data from patients treated in Pennsylvania-accredited trauma centers during 1989 were analyzed. TRISS expected and unexpected survivors (1.6% of all survivors) differed in many ways. Unexpected survivors were more than twice as likely to have been transferred from a nondesignated trauma center (45.8% vs. 22.8%, p < 0.001). Unexpected survivors had significantly higher frequencies of motor vehicle injuries (56.2% vs. 38.3%, p < 0.001), pedestrian injuries (9.6% vs. 5.4%, p < 0.01), and gunshot wounds (7.3% vs. 4.7%, p < 0.01). Expected survivors were injured more frequently in falls (26.1% vs. 10.8%, p < 0.001) and were less frequently male (64.5% vs. 75%, p < 0.001). Unexpected survivors had significantly longer average hospital stay (29.6 s vs. 9.3 days, p < 0.001) and more frequent (98.8% vs. 36.8%, p < 0.001) and longer average stays in the ICU (13.3 s vs. 4.1 days, p < 0.001). The percentage of unexpected survivors discharged to rehabilitation centers (61.9%) was significantly greater than that for expected survivors (8.7%), (p < 0.001). Unexpected survivors were more frequently judged "completely dependent" in five measures of functional disability than expected survivors. We conclude that unexpected survivors are a seriously injured and clinically relevant patient set, not just a statistical phenomenon.     

Prevalence of signs and symptoms of ocular surface disease in individuals treated and not treated with glaucoma medication

Background: To determine the prevalence of signs and symptoms of ocular surface disease in two hospital‐based cohorts; glaucoma patients and non‐glaucoma patients. Design: A cross‐sectional, comparative case series. Participants: Glaucoma patients (n = 300) prescribed topical glaucoma medications for ≥6 months were compared with control patients (n = 100) who were not applying prescribed topical medications. Methods: A validated self‐report questionnaire was used to elicit the extent of ocular symptoms. Signs of ocular surface and eyelid disease were assessed along with medication history. Main Outcome Measures: Signs and symptoms of ocular surface pathology were determined including the tear film break‐up time, fluorescein staining of the cornea and conjunctiva, meibomian gland dysfunction and Schirmer's test. Results: A significant increase in the prevalence of ocular surface disease signs was observed in the glaucoma population, 70.3%, compared with controls, 33% (P < 0.001). The overall prevalence of clinically significant ocular surface disease symptoms was not significantly different between cohorts, 30.7% versus 24.0%, respectively (P = 0.252). Logistic regression analysis showed that the number of anti‐glaucoma medications and duration of therapy were key predictors of significant ocular surface disease signs in the glaucoma group. There was no significant correlation between signs and symptoms of ocular surface disease in either group after adjusting for age and gender. Conclusions: Signs and symptoms of ocular surface disease are relatively common in older patients, but signs of ocular surface disease are significantly higher in individuals who instil topical glaucoma therapy.