Risk for falls in the elderly. Role of activities of daily living and of the subjective assessment of health status. A case-control study

Prevention and treatment of falls in the elderly are today important questions the primary care physicians has to face. It is known that falls are associated with numerous factors related to health status and demographic variables. The role played by the activities of daily living (ADL) and by a negative subjective health rating of one's own health status, and how both could increase the incidence of diseases due to home accidents, is less known. This case-control study carried out in the accident ward of S. Camillo Hospital in Rome, studied 110 elderly patients, who suffered from fractures caused by falls. The main goal was to identify the possible associations among falls, ADL and lower limb mobility, as well as studying the importance of a positive subjective health rating to prevent these accidents. Controls have been selected in other wards of the same hospital and in an out-patient's department. Results show that the risk of falling is associated with previous falls (odds ratio = 3.81), with poor mobility at home (OR = 2.49), outside home (OR = 2.06), out of one's own area (OR = 1.74), and with a negative subjective health rating (OR 3.33). Multivariate analysis has pointed out that a negative subjective health rating keeps being a statistically significant risk factor for falls (OR = 2.86), independently from the objective health conditions of the subject. Such a negative subjective rating often develops itself just as a consequence of a previous fall without injuries.     

A new 34-kilodalton isoform of human fibroblast growth factor 2 is cap dependently synthesized by using a non-AUG start codon and behaves as a survival factor

Four isoforms of human fibroblast growth factor 2 (FGF-2) result from alternative initiations of translation at three CUG start codons and one AUG start codon. Here we characterize a new 34-kDa FGF-2 isoform whose expression is initiated at a fifth initiation codon. This 34-kDa FGF-2 was identified in HeLa cells by using an N-terminal directed antibody. Its initiation codon was identified by site-directed mutagenesis as being a CUG codon located at 86 nucleotides (nt) from the FGF-2 mRNA 5' end. Both in vitro translation and COS-7 cell transfection using bicistronic RNAs demonstrated that the 34-kDa FGF-2 was exclusively expressed in a cap-dependent manner. This contrasted with the expression of the other FGF-2 isoforms of 18, 22, 22.5, and 24 kDa, which is controlled by an internal ribosome entry site (IRES). Strikingly, expression of the other FGF-2 isoforms became partly cap dependent in vitro in the presence of the 5,823-nt-long 3' untranslated region of FGF-2 mRNA. Thus, the FGF-2 mRNA can be translated both by cap-dependent and IRES-driven mechanisms, the balance between these two mechanisms modulating the ratio of the different FGF-2 isoforms. The function of the new FGF-2 was also investigated. We found that the 34-kDa FGF-2, in contrast to the other isoforms, permitted NIH 3T3 cell survival in low-serum conditions. A new arginine-rich nuclear localization sequence (NLS) in the N-terminal region of the 34-kDa FGF-2 was characterized and found to be similar to the NLS of human immunodeficiency virus type 1 Rev protein. These data suggest that the function of the 34-kDa FGF-2 is mediated by nuclear targets.     

Rat liver transport and biotransformation of a cytostatic complex of bis-cholylglycinate and platinum (II)

Dobutamine is used as an alternative to exercise in conjunction with 99mTc-sestamibi SPECT perfusion imaging for detection of coronary artery disease. However, the use of quantitative dobutamine 99mTc-sestamibi SPECT imaging for enhanced detection of coronary stenosis has not been established. The goal of this study is to examine the effects of dobutamine stress on regional myocardial blood flow and relative myocardial 99mTc-sestamibi activity in the presence of a single-vessel stenosis. METHODS: In six open-chest dogs with left circumflex artery stenosis, radiolabeled microspheres were injected during baseline, severe stenosis and peak dobutamine stress (10 microg/kg/min). Technetium-99m-sestamibi was injected intravenously at peak dobutamine. Hearts were excised 20 min after 99mTc-sestamibi injection for SPECT imaging and post-mortem gamma-well counting. RESULTS: Dobutamine significantly increased heart rate, rate-pressure product and the first derivative of left ventricular pressure. Ischemic zone (left circumflex) myocardial blood flows (in ml/min/g) were: baseline, 0.92 +/- 0.15; stenosis, 0.65 +/- 0.16; and dobutamine, 1.19 +/- 0.38. Nonischemic zone myocardial blood flows were: baseline, 0.99 +/- 0.18; stenosis, 1.01 +/- 0.12; and dobutamine, 1.94 +/- 0.32 (p < 0.01 versus stenosis). Ischemic flows, expressed as percentages of nonischemic flows, were: baseline, 94% +/- 2%; stenosis, 63% +/- 11% (p < 0.05 versus baseline) and dobutamine, 60% +/- 12% (p was not significant versus stenosis). Technetium-99m-sestamibi activity in the ischemic zone (75% +/- 6% nonischemic) underestimated the relative flow deficit produced during dobutamine stress (p = 0.056). Myocardial 99mTc-sestamibi activity correlated with flow when flow was less than 1.0 ml/min/g. At higher flow ranges (1.0 ml/min/g-3.5 ml/min/g), 99mTc-sestamibi did not track flow. CONCLUSION: In a canine model of flow-limiting, single-vessel stenosis, dobutamine (10 microg/kg/min) did not augment flow heterogeneity. In addition, relative myocardial 99mTc-sestamibi activity underestimated microsphere flow at higher flows induced by dobutamine, leading to underestimation of ischemia. These findings suggest that dobutamine stress 99mTc-sestamibi scintigraphy may underestimate the relative flow deficit.     

Surveillance of tuberculosis in Europe. Working Group of the World Health Organization (WHO) and the European Region of the International Union Against Tuberculosis and Lung Disease (IUATLD) for uniform reporting on tuberculosis cases

Consensus-based recommendations have been developed by a Working Group of the World Health Organization (WHO) and the European Region of the International Union Against Tuberculosis and Lung Disease (IUATLD) on uniform reporting of tuberculosis surveillance data in the countries of Europe. A uniform case definition and a minimum set of variables for reporting on each case have been agreed which, when collated on a national basis, will allow comparison of the epidemiology of tuberculosis in different European countries. The Working Group recommends that the case definition includes "definite" cases, where the diagnosis has been confirmed by culture (or supported by microscopy findings in countries where diagnostic culture facilities are not available), and "other than definite cases" based on a clinical diagnosis of tuberculosis combined with the intention to treat with a full course of antituberculosis therapy. Both "definite" and "other than definite" cases should be notified by physicians and, in addition, laboratories should be required to report "definite" cases. The minimum set of variables to be collected on each case of tuberculosis should include: date of starting treatment, place of residence, date of birth, gender, and country of origin, to characterize the patient. Recommended disease-specific variables include: site of disease, bacteriological status (microscopy and culture), and history of previous antituberculosis chemotherapy. The minimum set of variables should be collated on all patients and should be as complete as possible. Additional variables may be collected for individual, local or national purposes, but, in general, completeness of reporting on cases is likely to be better if the information requested is kept to a minimum. Timely reporting of cases is essential for appropriate public health action. Cases should be reported to the health authority at the local and/or regional level within 1 week of starting treatment. Individual-case based information should be reported to the national level by the local or regional level. Feedback to reporters is essential. At the national level, preliminary quarterly reports should be produced and final reports should be published annually.     

Identification by STS PCR screening of a microdeletion in Xp21.3-22.1 associated with non-specific mental retardation

X-linked non-specific mental retardation (MRX) is a heterogeneous condition in which mental retardation (MR) appears to be the only consistent manifestation. The genetic and phenotypic heterogeneity exclude any possibility of pooling families and, therefore, of fine-mapping the related disease genes. In order to identify genomic critical regions involved in the MRX condition assigned to Xp21.3-22.1 region, we have implemented the PCR screening of non fragile X MR patients for the presence of deletions in this region. The amplification by PCR of 12 markers located between POLA and DXS704 using genomic DNA from 192 MR males led to the identification, in a 9 year old mentally retarded boy, of a microdeletion which extends from DXS1202 to DXS1065. None of the known genes, POLA, MAGE genes cluster, DAX1, GK and DMD, that map in the Xp21.3-22.1 region is affected by this deletion. This approach, which could easily be applied to several other MRX loci, allowed not only a confirmation of the presence of a potential locus in Xp21.3-22.1 involved in non-specific mental retardation, but also a better definition of the genomic critical region corresponding to this locus.     

ThioTEPA pharmacokinetics during intravesical chemotherapy: the influence of dose and volume of instillate on systemic uptake and dose rate to the tumour

Hereditary tyrosinaemia type I (HTI), an autosomal recessive inborn error of metabolism, is caused by a deficiency of the enzyme fumarylacetoacetate hydrolase. The highest incidence of HTI is observed in the Saguenay-Lac-St-Jean region (SLSJ) (Québec, Canada), where 1 out of 22 individuals is thought to be a carrier. A splice mutation (IVS12 + 5G-->A) has recently been identified in this particular region. Here, we have determined the frequency of this mutation in a population of obligate carriers from the SLSJ region by allele-specific oligonucleotide hybridization and a method using a restriction enzyme digestion. Over 95 per cent of the HTI carriers were found to have the IVS12 + 5G-->A splice mutation. Screening for this mutation based on the two methods reported here is thus a reliable and rapid way of detecting carriers of hereditary tyrosinaemia type I in that region at high risk.     

DNA-damaging steroidal alkaloids from Eclipta alba from the suriname rainforest1

Bioassay-guided fractionation of the MeOH extract of Eclipta alba using three yeast strains (1138, 1140, and 1353) resulted in the isolation of eight bioactive steroidal alkaloids (1-8), six of which are reported for the first time from nature. The major alkaloid was identified as (20S)(25S)-22,26-imino-cholesta-5,22(N)-dien-3beta-ol (verazine, 3), while the new alkaloids were identified as 20-epi-3-dehydroxy-3-oxo-5,6-dihydro-4,5-dehydroverazine (1), ecliptalbine [(20R)-20-pyridyl-cholesta-5-ene-3beta,23-diol] (4), (20R)-4beta-hydroxyverazine (5), 4beta-hydroxyverazine (6), (20R)-25beta-hydroxyverazine (7), and 25beta-hydroxyverazine (8). Ecliptalbine (4), in which the 22,26-imino ring of verazine was replaced by a 3-hydroxypyridine moiety, had comparable bioactivity to verazine in these assays, while a second alkaloid (8) showed good activity against Candida albicans. All the alkaloids showed weak cytotoxicity against the M-109 cell line.     

In vitro site-specific integration of bacteriophage DNA catalyzed by a recombinase of the resolvase/invertase family

The genome of the broad host range Streptomyces temperate phage, phiC31, is known to integrate into the host chromosome via an enzyme that is a member of the resolvase/invertase family of site-specific recombinases. The recombination properties of this novel integrase on the phage and Streptomyces ambofaciens attachment sites, attP and attB, respectively, were investigated in the heterologous host, Escherichia coli, and in an in vitro assay by using purified integrase. The products of attP/B recombination, i.e., attL and attR, were identical to those obtained after integration of the prophage in S. ambofaciens. In the in vitro assay only buffer, purified integrase, and DNAs encoding attP and attB were required. Recombination occurred irrespective of whether the substrates were supercoiled or linear. A mutant integrase containing an S12F mutation was completely defective in recombination both in E. coli and in vitro. No recombination was observed between attB/attB, attP/attP, attL/R, or any combination of attB or attP with attL or attR, suggesting that excision of the prophage (attL/R recombination) requires an additional phage- or Streptomyces-encoded factor. Recombination could occur intramolecularly to cause deletion between appropriately orientated attP and attB sites. The results show that directionality in phiC31 integrase is strictly controlled by nonidentical recombination sites with no requirement to form the topologically defined structures that are more typical of the resolvases/invertases.     

T-cell and monocyte subsets, inflammatory molecules, rejection, and hemodynamics early after cardiac transplantation

BACKGROUND: In the early period after cardiac transplantation, differential diagnosis of graft failure due to rejection, infection, and other causes is important but difficult. METHODS: In 22 consecutive patients undergoing heart transplantation, we prospectively determined levels of interleukin-6 as well as T-cell and monocyte subsets at eight points in time during biopsy and right heart catheterization and within 12 hr of echocardiography during the first 3 months after transplantation. RESULTS: Worse hemodynamic parameters, as characterized by dichotomization according to median values (pulmonary capillary wedge pressure >10 mmHg, mean pulmonary arterial pressure > 18 mmHg, pulmonary vascular resistance > 115 dyn x sec x cm(-5), right atrial pressure > 5 mmHg, cardiac index <3 L/min/m2, early mitral deceleration time < 135 msec, and isovolumic relaxation time <80 msec), were associated with higher levels of interleukin-6, C-reactive protein, polymorphonuclear cells, CD71+/CD14+ monocytes, and IgM levels and, in contrast, with lower levels of immunocompetence markers such as CD3+ T cells, CD4+ T cells, CD8+ T cells, CD3+/CD25+ T cells, CD4+/ CD45RO+ T cells, NK cells, and lower biopsy scores. CONCLUSION: Early after cardiac transplantation, elevated levels of inflammatory cells and soluble inflammatory molecules and lower levels of immunocompetence markers are associated with impaired allograft function in the absence of cellular rejection.