Wandering: a significant problem among community-residing individuals with Alzheimer's disease

This study evaluated the frequency, predictors, and effects of wandering in a population-based sample of 193 individuals with Alzheimer's disease (AD). Although wandering occurred in subjects at all levels of cognitive impairment, analysis of variance indicated that for the group as a whole, greater frequency of wandering was associated with significantly more impairment in cognition, day-to-day functioning, and behavior. Caregiver distress also increased significantly with increased frequency of wandering. Logistic regression modeling identified functional impairment and disruptive behavior problems as the strongest independent predictors of wandering occurring within the past week. Cluster analysis revealed four characteristic groups of wanderers that represented a continuum of wandering frequency, each having a unique pattern of other behavioral disturbances. Based on this analysis, we recommend further evaluation and the development of possible treatment strategies that address the individual differences found among AD patients who wander.     

Inhibitory effect of adrenomedullin (ADM) on the aldosterone response of human adrenocortical cells to angiotensin-II: role of ADM(22-52)-sensitive receptors

Human adrenomedullin (ADM) is a 52-amino acid hypotensive peptide, which possesses a disulfide bridge-formed six-membered ring in 16-21 position. The ring structure, and both the N- and C-terminal amino-acid sequences seem to play a key role in the vascular effects of ADM(1-52), and we have investigated whether the same is true for the inhibitory effect of this peptide on the aldosterone response of zona glomerulosa (ZG) cells to angiotensin-II (ANG-II). Autoradiography showed the presence of abundant [125I]ADM(1-52) binding sites in the ZG of human adrenals, which were displaced not only by cold ADM(1-52), but also by both ADM(13-52) and ADM(22-52); ADM fragments 1-12, 15-22 and 16-31 were ineffective. ADM(1-52) and ADM(13-52), but not other fragments, concentration-dependently inhibited ANG-II-stimulated aldosterone secretion of dispersed human adrenocortical cells. The aldosterone antisecretagogue actions of ADM(1-52) and ADM(13-52) were counteracted by ADM(22-52) in a concentration-dependent manner, while other ADM fragments were ineffective. In light of these findings the following conclusions could be drawn: (i) human ZG cells are provided with ADM(22-52)-sensitive receptors; (ii) the six-membered ring structure and the C-terminal, but not N-terminal, amino-acid sequence are both essential for ADM(1-52) to exert its antimineralocorticoid action; and probably (iii) the C-terminal sequence is needed for ADM(1-52) to bind its ZG receptors, while the ring structure is required for the receptor activation.     

Interaction of lipophilic ions with the plasma membrane of mammalian cells studies by electrorotation

The electrical properties of biological and artificial membranes were studied in the presence of a number of negatively charged tungsten carbonyl complexes, such as [W(CO)5(CN)]- , [W(CO)5(NCS)]-, [W2(CO)10(CN)]-, and [W(CO)5(SCH2C6H5)]-, using the single-cell electrorotation and the charge-pulse relaxation techniques. Most of the negatively charged tungsten complexes were able to introduce mobile charges into the membranes, as judged from electrorotation spectra and relaxation experiments. This means that the tungsten derivatives act as lipophilic anions. They greatly contributed to the polarizability of the membranes and led to a marked dielectric dispersion (frequency dependence of the membrane capacitance and conductance). The increment and characteristic frequency of the dispersion reflect the structure, environment, and mobility of the charged probe molecule in electrorotation experiments with biological membranes. The partition coefficients and the translocation rate constants derived from the electrorotation spectra of cells agreed well with the corresponding data obtained from charge-pulse experiments on artificial lipid bilayers.     

Congenital dyserythropoietic anaemia: report of three cases

Between January 1985 and June 1992, the Paediatric Department of Hospital Universiti Sains Malaysia has diagnosed congenital dyserythropoietic anaemia in three children, two of whom were siblings. The age of onset ranged from 1 to 3 years. All of them became transfusion-dependent before the age of 4 months. One of them was successfully treated with bone marrow transplantation.     

In vitro production of parathyroid hormone-related protein by cholesteatoma and normal skin

Severe inflammation and infection of the middle ear occasionally results in clinical evidence of bone resorption but with the addition of the cholesteatoma epithelium it becomes inevitable. This study examined production by the cholesteatoma epithelium of a bone resorbing factor, namely parathyroid hormone-related protein (PTH-rP), which would not be expected in inflammatory states alone. PTH-rP was detected in the conditioned medium of primary and secondary cell cultures derived from 12 cholesteatoma biopsies. The levels of PTH-rP were significantly greater than in control cultures of cells derived from normal scalp tissue. Production by the cholesteatoma epithelium may explain the increased incidence of bone resorption in this disease, particularly in cases where inflammation is minimal.     

Differences in the shedding of soluble TNF receptors between endotoxin-sensitive and endotoxin-resistant mice in response to lipopolysaccharide or live bacterial challenge

TNF-alpha plays a pivotal role in the pathogenesis of septic shock. It exerts its effects by binding two cell surface receptors, designated TNF-R I and II, also referred to as the p55 and p75 receptors, respectively. TNF-Rs are transmembrane proteins, which on cleavage of their extracellular domains, result in the release of soluble fragments (sTNF-R). sTNF-R levels increase markedly during infection, and may serve to modulate TNF-alpha bioactivity. The mechanisms regulating this process are uncertain. To investigate this, we measured sTNF-R release in endotoxin-sensitive C3H/HeN and endotoxin-resistant C3H/HeJ mice given LPS or live Gram-negative bacteria. In C3H/HeN mice, there was a rapid early response during the first 4 h, and a second peak at 8 h, particularly noticeable in the case of the p75 receptor. Prior administration of neutralizing Abs to TNF-alpha or IFN-gamma had no effect on receptor shedding. Surprisingly, C3H/HeJ mice also responded to both bacterial challenge and to LPS by shedding sTNF-R; the magnitude and duration of the early response was not substantially different from C3H/HeN mice, although the second peak was absent. Peritoneal macrophages from C3H/HeN mice responded promptly (5 h) when stimulated with LPS in vitro, and by 22 h levels had increased five- to 10-fold. In contrast, cells from C3H/HeJ mice demonstrated only a very modest response at 22 h following maximal stimulation. The data suggest that there may be at least two separately regulated pathways that control sTNF-R shedding in these mice.