The association between unexplained falls and cardiac arrhythmias: A scoping literature review

BackgroundFalls in older adults are common. Age is a risk factor for falls and with an ageing population, presentation to the emergency department (ED) resulting from falls is rising. Reasons for falls in older adults are numerous and include cardiac arrhythmias. However, older patients who present with falls do not appear to be routinely screened for cardiac arrhythmias.ObjectivesTo determine the association between cardiac arrhythmias and unexplained falls in older adults presenting to the ED and to identify the processes for cardiac screening in patients presenting to the ED after an unexplained fall.MethodsA scoping literature review was conducted because of the scarce number of primary research articles using an investigational design to undertake a detailed systematic review. Several databases were searched using the search terms: emergency department; trauma centers; arrhythmias cardiac; fall; and accidental fall.Data sourcesA structured and systematic search using MEDLINE, Embase, and PubMed was conducted from 2002 to December 2017.ResultsFive quantitative studies were included in this review that reported on adults who presented to the ED after an unexplained fall. Several factors associated with falls and cardiac arrhythmias were extracted from the data. These included age, past history of falls, current medications, comorbidities, electrocardiography, and other cardiac findings.ConclusionFalls in the elderly population account for a significant number of presentations to the ED. A number of known factors are associated with falls in elderly patients, including cardiovascular causes, yet specific individualised factors are largely unknown. There is no routine screening process for the identification of cardiovascular risk factors in those who present to the ED with an unexplained fall. Further research is needed to identify specific cardiac factors associated with the risk of unexplained falls in this patient cohort and to transfer these findings into a routine screening process.     

Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice.

gamma-Glutamyl transpeptidase (GGT) is an ectoenzyme that catalyzes the first step in the cleavage of glutathione (GSH) and plays an essential role in the metabolism of GSH and GSH conjugates of carcinogens, toxins, and eicosanoids. To learn more about the role of GGT in metabolism in vivo, we used embryonic stem cell technology to generate GGT-deficient (GGTm1/GGTm1) mice. GGT-deficient mice appear normal at birth but grow slowly and by 6 weeks are about half the weight of wild-type mice. They are sexually immature, develop cataracts, and have coats with a gray cast. Most die between 10 and 18 weeks. Plasma and urine GSH levels in the GGTm1/GGTm1 mice are elevated 6-fold and 2500-fold, respectively, compared with wild-type mice. Tissue GSH levels are markedly reduced in eye, liver, and pancreas. Plasma cyst(e)ine levels in GGTm1/GGTm1 mice are reduced to approximately 20% of wild-type mice. Oral administration of N-acetylcysteine to GGTm1/GGTm1 mice results in normal growth rates and partially restores the normal agouti coat color. These findings demonstrate the importance of GGT and the gamma-glutamyl cycle in cysteine and GSH homeostasis.     

Oxidative metabolism of the human eosinophil

We have compared the oxidative metabolism of human eosinophils (80%-90% purity) to that of neutrophils. Hexose monophosphate (HMP) shunt activity of eosinophils was higher than that of neutrophils under either resting or phagocytizing conditions. Eosinophil HMP shunt activity also was stimulated by phorbol myristate acetate, a membrane- active agent. Eosinophils showed a marked incorporation of 125I into trichloroacetic acid-insoluble material under resting conditions, which increased markedly during phagocytosis. Eosinophils likewise showed a greater reduction of nitroblue tetrazolium dye during phagocytosis than did neutrophils. Measurement of other parameters of oxidative metabolism indicated that eosinophils generated superoxide anion following phagocytosis and also elicited a burst of chemiluminescence similar to that observed during phagocytosis by neutrophils. Measurement of NADPH oxidase activity demonstrated that this enzyme was 3-6 times more active in fractions isolated from eosinophils than in corresponding fractions isolated from neutrophils; this was observed over a range of substrate concentrations. The eosinophil enzyme sedimented differently than the neutrophil enzyme with differential centrifugation; neither showed sedimentation characteristics of peroxidase. These data indicate that eosinophils possess a similar, although in some ways more potent, oxidative burst than neutrophils and are consistent with a role for NADPH oxidase in the initiation of that burst.     

Allelotyping of butadiene-induced lung and mammary adenocarcinomas of B6C3F1 mice: frequent losses of heterozygosity in regions homologous to human tumor-suppressor genes.

To identify the potential involvement of tumor-suppressor gene inactivation during neoplastic development in B6C3F1 mice, genetic losses were determined from allelotypes of butadiene-induced lung and mammary adenocarcinomas. By using length polymorphisms in restriction fragments and simple sequence repeats, or "microsatellites," markers on each autosome were analyzed for allele losses in tumor DNAs. Losses of heterozygosity on chromosome 11 were observed at several loci surrounding the p53 tumor-suppressor gene (Trp53) in 12 of 17 mammary tumors and 2 of 8 lung tumors. Although most of these alterations appeared to result from nondisjunction, at least two examples of somatic recombination or deletion were also observed. Southern analysis revealed a homozygous deletion of the remaining Trp53 allele of one of these mammary tumors. Losses of heterozygosity were also detected at the Rb-1 tumor-suppressor gene in 7 of 17 mammary tumors and 1 lung tumor. Finally, frequent allele losses were observed on chromosome 4 in lung tumors. Analysis of nine chromosome 4 loci defined an interstitial deletion containing the Ifa gene cluster in one of the lung tumors. A tumor-suppressor gene was previously mapped to this region of chromosome 4 in studies with somatic cell hybrids. In addition, homozygous deletions have been reported in a homologous region of human chromosome 9p for acute lymphocytic leukemias, glioblastomas, melanomas, and lung carcinomas. These findings suggest that the inactivation of tumor-suppressor genes including Trp53, Rb-1, and an unidentified gene on chromosome 4 plays a significant role during carcinogenesis in mice.     

Three-month B vitamin supplementation in pre-school children affects folate status and homocysteine,but not cognitive performance

Background

Suboptimal vitamin B status might affect cognitive performance in early childhood. We tested the hypothesis that short-term supplementation with folic acid and selected B vitamins improves cognitive function in healthy children in a population with relatively low folate status.

Methods

We screened 1,002 kindergarten children for suboptimal folate status by assessing the total urinary para-aminobenzoylglutamate excretion. Two hundred and fifty low ranking subjects were recruited into a double blind, randomized, controlled trial to receive daily a sachet containing 220 μg folic acid, 1.1 mg vitamin B₂, 0.73 mg B₆, 1.2 μg B₁₂ and 130 mg calcium, or calcium only for 3 months. Primary outcomes were changes in verbal IQ, short-term memory and processing speed between baseline and study end. Secondary outcomes were urinary markers of folate and vitamin B₁₂ status, acetyl-para-aminobenzoylglutamate and methylmalonic acid, respectively, and, in a subgroup of 120 participants, blood folate and plasma homocysteine.

Results

Pre- and post-intervention cognitive measurements were completed by 115 children in the intervention and 122 in the control group. Compared to control, median blood folate increased by about 50 % (P for difference, P < 0.0001). Homocysteine decreased by 1.1 μmol/L compared to baseline, no change was seen in the control group (P for difference P < 0.0001) and acetyl-para-aminobenzoylglutamate was 4 nmol/mmol higher compared to control at the end of the intervention (P < 0.0001). We found no relevant differences between the groups for the cognitive measures.

Conclusion

Short-term improvement of folate and homocysteine status in healthy children does not appear to affect cognitive performance.     

Predictive utility of cyclo-oxygenase-2 expression by colon and rectal cancer

Background

Cyclo-oxygenase-2 (COX-2), an inducible enzyme expressed in areas of inflammation, is a target of interest for colorectal cancer therapy. Currently, the predictive significance of COX-2 in colorectal cancer remains unclear.

Methods

Tissue microarrays were constructed using 118 colon cancer and 85 rectal cancer specimens; 44 synchronous metastatic colon cancer and 22 rectal cancer lymph nodes were also evaluated. COX-2 expression was assessed by immunohistochemistry. Univariate analysis was used to determine the predictive significance of clinicopathologic variables. Overall survival, disease-specific survival, and disease-free survival were the main outcomes examined.

Results

COX-2 was found to be expressed in 93% of colon cancers and 87% of rectal cancers. Decreased COX-2 expression was related to decreased disease-specific survival (P = .016) and decreased disease-free survival (P = .019) in the rectal cancer cohort but not in the colon cancer cohort.

Conclusions

COX-2 expression has predictive utility for management of rectal but not colon cancer.     

Clinical utility of type 1 growth factor receptor expression in colon cancer

BACKGROUND: To evaluate the expression pattern and prognostic significance of the type 1 growth factor receptor (T1GFR) family in colon carcinoma. METHODS: Tissue microarrays were constructed using 127 tumor samples and 47 metastatic lymph nodes and T1GFR family expression was determined by immunohistochemistry. Univariate and multivariate analyses examined clinicopathologic variables for prognostic significance, and the correlation between primary and lymph node expression was determined by Spearman correlation. RESULTS: Overexpression of HER-1, HER-2, HER-3, and HER-4 in tumor samples was 32%, 1%, 12%, and 37%, respectively, and 30%, 0%, 11%, and 24% in nodal samples, respectively. On multivariate analysis, positive margins, lymphatic invasion, and HER-3 expression were significant predictors of survival outcome. There was significant correlation between tumor and regional lymph node expression for the T1GFR family members. Tumor HER-3 expression was associated with lymphatic invasion and distant recurrence. CONCLUSIONS: Tumor HER-3 expression has prognostic utility in individuals with colon carcinoma. Correlation between tumor and lymph node expression of T1GFR family members suggests that tumor receptor status may guide targeted therapy selection.