Evaluation of investigations to diagnose the cause of dizziness in elderly people: a community based controlled study.

OBJECTIVE: To compare the findings in dizzy elderly people with those in controls of a similar age to identify which investigations differentiate dizzy from non-dizzy patients and to design an investigational algorithm. DESIGN: Community based study of clinical and laboratory findings in dizzy and control elderly people. SETTING: Research outpatient clinic at a teaching hospital. SUBJECTS: 149 dizzy and 97 control subjects aged over 65 years recruited from a community survey and articles in the local press. MAIN OUTCOME MEASURES: Findings on physical examination, blood testing, electrocardiography (at rest and over 24 hours), electronystagmography, posturography, and magnetic resonance imaging of head and neck (125 (84%) dizzy subjects and 86 (89%) controls); hospital anxiety and depression score; responses to hyperventilation, carotid sinus massage, and the Hallpike manoeuvre. RESULTS: Blood profile, electrocardiography, electronystagmography, and magnetic resonance imaging failed to distinguish dizzy from control subjects because of the frequency of asymptomatic abnormalities in controls. Posturography and clinical assessment (physical examination, dizziness provocation, and psychological assessment) showed significant differences between the groups. A cause of the dizziness was identified from clinical diagnostic criteria based on accepted definitions in 143 subjects, with 126 having more than one cause. The most common diagnoses were central vascular disease (105) and cervical spondylosis (98), often accompanied by poor vision and anxiety. CONCLUSION: Expensive investigations are rarely helpful in dizzy elderly people. The cause of the dizziness can be diagnosed in most cases on the basis of a thorough clinical examination without recourse to hospital referral.     

Genistein activates CFTR-mediated Cl(-) secretion in the murine trachea and colon

The action of the isoflavonegenistein on the cystic fibrosis transmembrane conductance regulator(CFTR) has been studied in many cell systems but not in intact murinetissues. We have investigated the action of genistein on murine tissuesfrom normal and cystic fibrosis (CF) mice. Genistein increased theshort-circuit current (I_sc) in tracheal(16.4 ± 2.8 µA/cm²) and colonic (40.0 ± 4.4 µA/cm²) epithelia of wild-type mice. This increase wasinhibited by furosemide, diphenylamine-2-carboxylate, andglibenclamide, but not by DIDS. In contrast, genistein produced nosignificant change in the I_sc of the trachealepithelium (0.9 ± 1.1 µA/cm²) and decreased theI_sc of colons from CF null (13.1 ± 2.3 µA/cm²) and F508 mice (10.3 ± 1.3 µA/cm²). Delivery of a human CFTRcDNA-liposome complex to the airways of CF null mice restored thegenistein response in the tracheas to wild-type levels. Tracheas fromF508 mice were also studied: 46% of trachea showed no response togenistein, whereas 54% gave an increase in I_scsimilar to that in wild type. We conclude that genistein activatesCFTR-mediated Cl secretion in the murine trachea anddistal colon.

     

X-ray microanalysis of airway surface liquid in the mouse

The ionic composition of airway surface liquid (ASL) has been debated, and, in particular for the mouse, a wide range of values has been published. Two techniques were developed to measure the elemental composition of the ASL. X-ray microanalysis of ASL was carried out at low temperature on trachea removed from isoflurane-anesthetized animals and shock-frozen. In the second technique, dextran beads were placed on top of the epithelium of the trachea removed from pentobarbital-anesthetized animals, left to equilibrate with the ASL, dried, and subjected to X-ray microanalysis. Both techniques showed that mouse tracheal ASL has significantly lower concentrations of Na and Cl (approximately 60-80 mM) than serum. Differences between the two techniques were due to different sampling of mucus. CFTR(-/-) mice had significantly higher concentrations of Na and Cl in their ASL than age-matched controls. Pilocarpine or isoproterenol stimulation significantly reduced the ion concentrations in tracheal ASL. ASL was also collected with the dextran bead method from the nasal cavity in situ in pentobarbital-anesthetized animals. In control animals, the elemental composition of nasal fluid was similar to that of tracheal ASL. Pilocarpine stimulation caused a significant increase in Na, Cl, and K; stimulation with isoproterenol or phenylephrine caused a significant increase only in K. It is concluded that mouse ASL under unstimulated conditions is hypotonic, which may be related to the relative paucity of submucosal glands in the mouse trachea.     

Complementation of null CF mice with a human CFTR YAC transgene.

We have made transgenic mice carrying a 320 kb YAC with the intact human cystic fibrosis transmembrane regulator (CFTR) gene. Mice that only express the human transgene were obtained by breeding with Cambridge null CF mice. One line has approximately two copies of the intact YAC. Mice carrying this transgene and expressing no mouse cftr appear normal and breed well, in marked contrast to the null mice, where 50% die by approximately 5 days after birth. The chloride secretory responses in these mice are as large or larger than in wild-type tissues. Expression of the transgene is highly cell type specific and matches that of the endogenous mouse gene in the crypt epithelia throughout the gut and in salivary gland tissue. However, there is no transgene expression in some tissues, such as the Brunner's glands, where it would be expected. Where there are differences between the mouse and human pattern of expression, the transgene follows the mouse pattern. We have thus defined a cloned fragment of DNA which directs physiological levels of expression in many of the specific cells where CFTR is normally expressed.     

Crop husbandry activities and wild plant gathering,use and consumption at the EPPNB Tell Qarassa North (south Syria)

The Early Pre-Pottery Neolithic B (EPPNB) in southwest Asia is a fundamental period in research on the origins of domesticated plants. However, there are few archaeobotanical data with which to characterise the plant-based subsistence and crop husbandry activities during this time, which hinders the understanding of the factors that triggered the appearance of plant domestication. In this paper, analyses of non-woody plant macro-remains provide new insights into subsistence activities such as crop cultivation (husbandry activities and storage) and plant use (wild plant gathering and food preparation) during the EPPNB at Tell Qarassa North (south Syria). We make comparisons between Tell Qarassa North and the evidence at earlier and later periods as to how plants were used, and highlight similarities and differences in the practices attested, as well as describing some of the consequences that these plant-related activities may have had in terms of labour and social organization during EPPNB.     

The orphan adhesion-GPCR GPR126 is required for embryonic development in the mouse

Adhesion-GPCRs provide essential cell-cell and cell-matrix interactions in development, and have been implicated in inherited human diseases like Usher Syndrome and bilateral frontoparietal polymicrogyria. They are the second largest subfamily of seven-transmembrane spanning proteins in vertebrates, but the function of most of these receptors is still not understood. The orphan Adhesion-GPCR GPR126 has recently been shown to play an essential role in the myelination of peripheral nerves in zebrafish. In parallel, whole-genome association studies have implicated variation at the GPR126 locus as a determinant of body height in the human population. The physiological function of GPR126 in mammals is still unknown. We describe a targeted mutation of GPR126 in the mouse, and show that GPR126 is required for embryonic viability and cardiovascular development.