Executive dysfunction in Alzheimer's disease

Executive functioning was examined in 20 patients with Alzheimer's disease (AD) and 20 normal elderly subjects. The results showed that AD patients present lower performance compared to control subjects in all executive tasks, confirming that some executive deficits may be present in the first stages of the disease. A factorial analysis suggested that these deficits can be related to two domains of the executive functions: the inhibition abilities and the capacity to co-ordinate simultaneously storage and processing of information. Moreover, the performance on these factors is correlated to different anterior and posterior cortical areas.     

Differentialdiagnose der orthostatischen Dysregulationen

Orthostatic circulatory disorders are frequently the cause of orthostatic intolerance, syncope or dangerous falls. A sufficient therapy should be based on a differential diagnosis by means of an active standing test or a tilt-table test. Three typical pathological reactions of blood pressure and heart rate can be differentiated. The hypoadrenergic orthostatic hypotension is characterised by an immediate drop in blood pressure (systolic drop > 20 mmHg below base line within 3 min) with or without compensatory tachycardia. It is caused by peripheral or central sympathetic dysfunction. Tachycardia (> 30 beats per minute above base line within 10 min) without significant blood pressure drop but with a fall of cerebral blood flow indicates a postural tachycardia syndrome. In general, there is no further somatic dysfunction. Increased venous pooling is thought to be the assumed pathomechanism. A reflex mechanism evokes the neurocardiogenic syncope after a certain time of standing: sympathetic inhibition yields a strong blood pressure drop and vagal activation bradycardia. Proved therapies include use of the mineralocorticoide fludrocortison (hypoadrenergic orthostatic hypotension), of the alpha-agonist midodrin (postural tachycardia syndrome) and of beta-blockers (neurocardiogenic syncope).     

The contribution of mechanoreceptive neurones in the gingival tissues to the masticatory-parotid salivary reflex in man

The masticatory-parotid salivary reflex has been studied in fully dentate subjects. Salivary flow was recorded by siting a modified Lashley cup over the orifice of the parotid duct on one side of the mouth. Subjects chewed on small pieces of silicone rubber for 1-min periods which resulted in a reflex secretion of parotid saliva. The secretion was greatest when the subject chewed on the same side of the mouth (ipsilateral) as the salivary flow was recorded. Less salivary flow resulted when the subjects chewed on the opposite side of the mouth (contralateral). Selected areas of the buccal or lingual gingival tissues were then anaesthetized on the side ipsilateral to the Lashley cup. Anaesthesia of the lingual and buccal gingival tissues together resulted in a reduction of salivary flow in response to similar chewing cycles. Anaesthesia of the lingual gingival tissues alone also resulted in a reduction of salivary flow, but anaesthesia of the buccal gingival tissues alone did not. During mastication it is likely that mechanoreceptors in the gingival tissues will be stimulated which may result in salivary flow. This requires further study as other mechanoreceptive neurones are also known to be involved in the masticatory-parotid salivary reflex.     

Factor V Leiden and hepatic artery thrombosis after liver transplantation

Factor V Leiden (FVL) and other thrombophilias can be acquired during liver transplantation and can have a significant impact on clinical outcomes as well as cost. Standard practice does not include screening deceased donors for heritable thrombophilias, even if they have a personal history of thrombosis. Here we report a case of hepatic artery thrombosis in a liver recipient whose native and donor livers were heterozygous for FVL. The patient subsequently underwent a successful retransplant. FVL and its variants are expressed phenotypically as activated protein C (APC) resistance. We believe that testing liver donors (deceased or living) for APC resistance - a surrogate marker for the most common liver-based thrombophilia - will reduce the incidence of thrombotic events by identifying a need for posttransplant prophylactic anticoagulation in patients at risk. The estimated cost of testing all liver donors in the US for APC resistance is less than the cost of two complications secondary to thrombosis. Testing for APC resistance may further improve outcome and reduce cost after liver transplantation.     

The role of external beam radiotherapy in the management of bone metastases

External beam radiotherapy is effective in the management of bone metastases for both local and more widespread pain. It is effective in spinal canal compression and pathological fracture where it also may have a prophylactic role. Single dose radiotherapy for bone metastases is a highly cost effective palliative treatment.     

Influence of day and night wear on surface properties of silicone hydrogel contact lenses and bacterial adhesion

PURPOSE: The aim of this study was to determine the effect of continuous wear on physicochemical surface properties of silicone hydrogel (S-H) lenses and their susceptibility to bacterial adhesion. METHODS: In this study, volunteers wore 2 pairs of either "lotrafilcon A" or "balafilcon A" S-H contact lenses. The first pair was worn continuously for a week and the second pair for 4 weeks. One lens of each pair was used for surface characterization and the other one for bacterial adhesion experiments. Lens surfaces were characterized by examination of their wettability, roughness, elemental composition, and proteins attached to their surfaces. Adhesion of Staphylococcus aureus 835 and Pseudomonas aeruginosa #3 to a lens was studied using a parallel plate flow chamber. RESULTS: Before use, the lotrafilcon A lens was rougher than the balafilcon A lens and had a lower water contact angle and a higher affinity for S. aureus 835. After wear, both lens types had similar water contact angles, whereas the differences in elemental surface composition decreased as well. S. aureus 835 adhered in higher numbers to worn balafilcon A lenses, whereas the opposite was seen for P. aeruginosa #3. The initial deposition rates of both bacterial strains to lotrafilcon A lenses decreased by wearing and were found to correlate significant (P < 0.001) with the surface roughness of worn lenses. CONCLUSIONS: In this study, the differences in surface properties between 2 types of S-H lenses were found to change after 1 week of continuous wear. Generally, bacteria adhered in lower numbers and less tenaciously to worn lenses, except S. aureus 835, adhering in higher numbers to worn balafilcon A lenses.     

Potent and orally bioavailable 8-bicyclo[2.2.2]octylxanthines as adenosine A1 receptor antagonists

In the search for a selective adenosine A1 receptor antagonist with greater aqueous solubility than the compounds currently in clinical trials as diuretics, a series of 1,4-substituted 8-cyclohexyl and 8-bicyclo[2.2.2]octylxanthines were investigated. The binding affinities of a variety of cyclohexyl and bicyclo[2.2.2]octylxanthines for the rat and human adenosine A1, A2A, A2B, and A3 receptors are presented. Bicyclo[2.2.2]octylxanthine 16 exhibited good pharmaceutical properties and in vivo activity in a rat diuresis model (ED50=0.3 mg/kg po). Optimization of the bridgehead substituent led to propionic acid 29 (BG9928), which retained high potency (hA1, Ki=7 nM) and selectivity for the adenosine A1 receptor (915-fold versus adenosine A2A receptor; 12-fold versus adenosine A2B receptor) with improved oral efficacy in the rat diuresis model (ED50=0.01 mg/kg) as well as high oral bioavailability in rat, dog, and cynomolgus monkey.     

Studies on condensed 1,4-dihydropyridine derivatives and their calcium modulatory activities

Hexahydroquinoline and furoquinoline derivatives were synthesized and their calcium modulatory activity was investigated on isolated rat ileum and lamb carotid artery. In addition, the in vitro hepatic microsomal biotransformation of one hexahydroquinoline derivative was studied in rat microsomes.     

Prevalence estimates of asthma or COPD from a health interview survey and from general practitioner registration: what's the difference?

BACKGROUND: The aim of this study was to compare prevalence estimates of asthma or chronic obstructive pulmonary disease (COPD) derived from self-report in a health interview survey and from general practitioners' (GPs') medical records, and to explain any differences. METHODS: the presence of asthma or COPD was measured by self-report in a random sample of 104 general practices in the Netherlands (n = 19 685) participating in the second Dutch National Survey of General Practice (DNSGP-2). This was compared with the presence of GP-diagnosed asthma or COPD in the same population as recorded using the International Classification of Primary Care by their GPs during a 12-month period. Gender, age, health insurance, ethnic background, educational level, tobacco exposure, and other symptoms and conditions were evaluated as explanatory variables using logistic models. RESULTS: The prevalence of self-reported asthma or COPD (9.7%) was almost twice as high as the prevalence based on GP information (5.2%). The medical records of patients who reported having asthma or COPD, without having a diagnosis in their medical records, usually included other respiratory conditions. Patients reporting no asthma or COPD but whose medical records carried a diagnosis of asthma or COPD, were relatively older (P < 0.01) and tended to be exposed to smoking in their home (P < 0.05). CONCLUSIONS: Two methods for estimating prevalence of asthma or COPD yielded different results: compared with GP medical records, self-reported prevalence shows an overestimation in people who suffer from other respiratory conditions and an underestimation in elderly persons living in a smoky environment.