The effects of weather and seasonality on hip fracture incidence in older adults

This study examined the effect of weather and seasonality on hipfracture incidence in older adults residing in New York City. A total off 66,346 patients aged > or = 65 years who sustained a fracture of the femoralneck or intertrochanteric region from 1985 to 1996 comprised the study population. Hip fractures were more likely to occur in the winter than in any of the other seasons (P<.001). Factors significantly correlated with hip fractureincluded minimum daily temperature (r=.167, P<.001), daily wind speed (r=.166, P<.001), maximum daily temperature (r=.155, P<.001), minutes of sunshine (r=.067, P<.01), and average relative humidity (r=.033, P=.03). A greater number of hip fractures occurred in colder months, withambient temperature rather than any adverse circumstances related to rainor snowfall associated most closely to injury. As most fractures occurredindoors, precipitation is less likely to play a part in hip fracture occurrence in this population.     

New and unusual O alleles at the ABO locus are implicated in unexpected blood group phenotypes

BACKGROUND: In the ABO blood group system mutations in the A gene may lead to weak A subgroups owing to a dysfunctional 3-alpha-N-acetylgalactosaminyltransferase. STUDY DESIGN AND METHODS: Blood and DNA were investigated to correlate weak A phenotypes with genotype, and an overrepresentation of the infrequent O2 allele was observed. Consequently, 57 available O2 alleles were examined in detail. RESULTS: Two new O2 alleles were identified having mutations resulting in Gly229Asp with or without Arg217Cys. A recently described O2 variant (488C>T; Thr163Met) was also found. Surprisingly, both the original and the variant O2 alleles were associated with either O or Aweak phenotypes. Three novel O alleles surfaced in six other samples with suspected A subgroups. These were A1-like alleles having nonsense mutations causing premature truncation at codons 56, 107, or 181. A second example of the rare O3 allele was also identified. A newly described O1 allele having 768C>A was found to be the third most frequent O allele among Swedish donors. Of the five novel O alleles, three were incorrectly interpreted as A1 following routine ABO genotyping. CONCLUSION: Apparent O alleles lacking 261delG may cause weak A expression on red blood cells and/or inhibit anti-A production. A hypothesis that exchange of genetic material between principally dissimilar O alleles during mitosis ("autologous chimerism") restores glycosyltransferase activity in some cells would explain this interesting phenomenon.     

What are the effects of maternal and pre-adult environments on ageing in humans, and are there lessons from animal models?

An open issue in research on ageing is the extent to which responses to the environment during development can influence variability in life span in animals, and the health profile of the elderly in human populations. Both affluence and adversity in human societies have profound impacts on survivorship curves, and some of this effect may be traceable to effects in utero or in infancy. The Barker Hypothesis that links caloric restriction in very early life to disruptions of glucose-insulin metabolism in later life has attracted much attention, as well as some controversy, in medical circles. It is only rarely considered by evolutionary biologists working on phenotypic plasticity, or by biogerontologists studying model organisms such as C. elegans or Drosophila. One crucial mechanism by which animals can respond in an adaptive manner to adverse conditions, for example in nutrition or infection, during development is phenotypic plasticity. Here we begin with a discussion of adaptive plasticity in animals before asking what such phenomena may reveal of relevance to rates of ageing in animals, and in humans. We survey the evidence for effects on adult ageing of environmental conditions during development across mammalian and invertebrate model organisms, and ask whether evolutionary conserved mechanisms might be involved. We conclude that the Barker Hypothesis is poorly supported and argue that more work in human populations should be integrated with multi-disciplinary studies of ageing-related phenomena in experimental populations of different model species that are subjected to nutritional challenges or infections during pre-adult development.     

A small-molecule inhibitor of isoprenylcysteine carboxyl methyltransferase with antitumor activity in cancer cells

Many key regulatory proteins, including members of the Ras family of GTPases, are modified at their C terminus by a process termed prenylation. This processing is initiated by the addition of an isoprenoid lipid, and the proteins are further modified by a proteolytic event and methylation of the C-terminal prenylcysteine. Although the biological consequences of prenylation have been characterized extensively, the contributions of prenylcysteine methylation to the functions of the modified proteins are not well understood. This reaction is catalyzed by the enzyme isoprenylcysteine carboxyl methyltransferase (Icmt). Recent genetic disruption studies have provided strong evidence that blocking Icmt activity has profound consequences on oncogenic transformation. Here, we report the identification of a selective small-molecule inhibitor of Icmt, 2-[5-(3-methylphenyl)-1-octyl-1H-indol-3-yl]acetamide (cysmethynil). Cysmethynil treatment results in inhibition of cell growth in an Icmt-dependent fashion, demonstrating mechanism-based activity of the compound. Treatment of cancer cells with cysmethynil results in mislocalization of Ras and impaired epidermal growth factor signaling. In a human colon cancer cell line, cysmethynil treatment blocks anchorage-independent growth, and this effect is reversed by overexpression of Icmt. These findings provide a compelling rationale for development of Icmt inhibitors as another approach to anticancer drug development.     

MRI measures and progression of cognitive decline in nondemented elderly attending a memory clinic

OBJECTIVE: To investigate whether MRI-based volumes of whole brain, medial temporal lobe and white matter hyperintensities (WMH) predict progression of cognitive decline in a sample of nondemented elderly. METHODS: Thirty-seven nondemented elderly attending a memory clinic and 28 elderly controls participated in this follow-up study. The average follow-up period was 1.8 years. Cognitive function was measured at baseline and follow-up with the Cambridge Cognitive Examination (CAMCOG). Baseline Magnetic Resonance Imaging (MRI) provided quantitative measures of whole brain, medial temporal lobe and WMH. Linear mixed models controlled for age and sex were used to assess the independent associations between MRI measures, baseline cognition, and annual decline in cognition. RESULTS: Medial temporal lobe volume was independently associated with baseline CAMCOG score (p < 0.01), whereas whole brain volume (p < 0.01) and WMH (p < 0.05) were associated with annual decline in CAMCOG score. CONCLUSIONS: These data suggest that regional damage to the medial temporal lobes underlies initial mild cognitive impairment, whereas more global brain changes, such as whole brain atrophy and WMH, contribute to further progression of cognitive decline.     

Agreement between four available algorithms to evaluate global systolic left and right ventricular function from tomographic radionuclide ventriculography and comparison with planar imaging

BACKGROUND AND AIM: Left and right ventricular ejection fractions (LVEF and RVEF) and end-diastolic and end-systolic volumes (LVEDV, RVEDV, LVESV and RVESV) can be calculated from tomographic radionuclide ventriculography (TRV). The aim of this study was to validate and compare these parameters obtained using four different TRV software programs (QBS, QUBE, 4D-MSPECT and BP-SPECT). METHODS: LVEF obtained from planar radionuclide ventriculography (PRV) was compared with LVEF obtained from TRV using the four different software programs in 166 patients. Furthermore, ventricular volumes obtained using TRV (QBS, QUBE and 4D-MSPECT) were compared with those obtained using BP-SPECT, the latter being the only method with the validation of ventricular volumes in the literature. RESULTS: The correlation of LVEF between PRV and TRV was good for all methods: 0.81 for QBS, 0.79 for QUBE, 0.71 for 4D-MSPECT and 0.79 for BP-SPECT. The mean differences+/-standard deviation (SD) were 3.16+/-9.88, 10.72+/-10.92, 3.43+/-11.79 and 2.91+/-10.39, respectively. The correlation of RVEF between BP-SPECT and QUBE and QBS was poor: 0.33 and 0.38, respectively. LV volumes calculated using QBS, QUBE and 4D-MSPECT correlated well with those obtained using BP-SPECT (0.98, 0.90 and 0.98, respectively), with mean differences+/-SD of 7.31+/-42.94, -22.09+/-36.07 and -40.55+/-39.36, respectively. RV volumes showed poorer correlation between QBS and BP-SPECT and between QUBE and BP-SPECT (0.82 and 0.57, respectively). CONCLUSION: LVEF calculated using TRV correlates well with that calculated using PRV, but is not interchangeable with the value obtained using PRV. Volume calculations (for left and right ventricle) and RVEF require further validation before they can be used in clinical practice.     

Sudden death: ectopic pregnancy mortality

OBJECTIVE: To describe the trends in ectopic pregnancy mortality in Michigan from 1985 through 1999 and compare to those of previous time periods. METHODS: We reviewed all cases of maternal mortality from ectopic pregnancy in Michigan from 1985 through 1999. We extracted data from death certificates, hospital inpatient and emergency department records, medical examiner autopsy reports, and reviews by the Michigan Maternal Mortality Study. The Health Data Development Section of the Michigan Department of Community Health provided data on live births and maternal deaths RESULTS: Of the 268 pregnancy-related deaths, 16 (6%) were caused by complications of ectopic pregnancy. Mean age at death was 27 (+/- 6) years. Thirteen deaths were to African-American women and 3 were to white women (P < .01). African-American women had an ectopic mortality ratio 18 times higher than white women (3.25/100,000 live births, compared with 0.18/100,000) Three cases of pregnancy-related death due to complications of ectopic pregnancy were considered preventable, and 2 others were of unknown preventability. CONCLUSION: Ectopic pregnancy treatment has changed in the last 20 years coincident with a decrease in maternal mortality from ectopic pregnancy. Sudden death was the presenting scenario in 75% of nonpreventable ectopic deaths, an increase from previous analyses. A large racial disparity is apparent. Ideally, pregnancy care should start as soon as possible after the first missed menses; however, systemwide changes are needed to create a new norm promoting early access to pregnancy care and promoting education and testing to rule out pregnancy abnormalities. LEVEL OF EVIDENCE: II-2     

The hospital organization of the future

The future of hospital Nuclear Medicine is triggered by the hospital organisation itself. In general, the hospital organisation of the present requires substantial changes in order to be competitive, economical, and abreast of the rapid progresses in medical developments and patient management. It also must be flexible to changes in health politics. In this special report an organisational hospital structure is outlined which may help encounter the challenging hospital future. Some hospitals have already implemented convincing changes, whereas others are far behind.