CCR5-Δ32 polymorphism—a possible protective factor from gait impairment amongst post-stroke patients

Background and purpose

Stroke and small vessel disease cause gait disturbances and falls. The naturally occurring loss-of-function mutation in the C-C chemokine receptor 5 gene (CCR5-Δ32) has recently been reported as a protective factor in post-stroke motor and cognitive recovery. We sought to examine whether it also influences gait and balance measures up to 2 years after stroke.

Method

Participants were 575 survivors of first-ever, mild–moderate ischaemic stroke or transient ischaemic attack from the TABASCO prospective study, who underwent a 3 T magnetic resonance imaging at baseline and were examined by a multi-professional team 6, 12 and 24 months after the event, using neurological, neuropsychological and mobility examinations. Gait rhythm and the timing of the gait cycle were measured by force-sensitive insoles. CCR5-Δ32 status and gait measures were available for 335 patients.

Results

CCR5-Δ32 carriers (16.4%) had higher gait speed and decreased (better) stride and swing time variability 6 and 12 months after the index event compared to non-carriers (p < 0.01 for all). The association remained significant after adjustment for age, gender, education, ethnicity and stroke severity.

Conclusions

Significant associations were found between gait measurements and CCR5-Δ32 loss-of-function mutation amongst stroke survivors. This is the first study showing that genetic predisposition may predict long-term gait function after ischaemic stroke.     

Synthesis and biological activity of CCK26-33-related analogues modified in position 31

The role of the amino acid in position 31 of cholecystokinin CCK26-33 in the recognition of central and peripheral receptors was investigated by replacement of methionine-31 by amino acids with side chains of various chemical nature. Thus, phenylalanine, alanine, glutamic acid, and ornithine and its analogue with the epsilon-amino group protected by a benzyloxycarbonyl group were introduced as X residues in Boc(Nle28,X31)-CCK27-33 since the related analogue Boc(Nle28,Nle31)-CCK27-33 was shown to be equipotent to CCK26-33. The binding properties to both mouse brain membranes and guinea pig pancreatic acini and the peripheral activities (amylase secretion and contractile potency on guinea pig ileum) were determined. Whereas the introduction of phenylalanine, alanine, or ornithine residues in position 31 led to compounds that still displayed peripheral agonist properties, the presence of a negative charge in the side chain of the amino acid in position 31 prevented the binding of the peptide to both pancreatic and brain binding sites. Introduction of Phe31 and Ala31 residues increased the specificity of the peptides for the central receptors. Interestingly, when the amine function in the side chain of the ornithine-31 was protected by a benzyloxycarbonyl group, an unusual high affinity for pancreatic binding sites was observed and the related analogue proved to be a new peripheral CCK antagonist.     

3-Methylglutaconic aciduria in “optic atrophy plus”

Behr's syndrome consists of recessively inherited infantile optic atrophy, together with chronic neurological disturbances such as ataxia, extrapyramidal dysfunction, and juvenile spastic paresis. This syndrome was found to be relatively common among Iraqi Jews. For our study, 18 such patients underwent metabolic study. All 18 showed abnormally elevated excretion of 3-methylglutaconic acid in their urine. The basic enzymatic defect is as yet unknown. We recommend that patients with early optic atrophy, and especially those with motor dysfunction, be examined for this organic aciduria.     

Bacteriolytic activity of human gingival exudate

We investigated the bacteriolytic activity of gingival crevicular fluid (CF) on¹⁴C-labeledStreptococcus faecalis, Streptococcus mutans, Staphylococcus aureus, and on whole dental plaque. CF was collected from 100 healthy donors pooled and centrifuged at 200g. CF supernate and a frozen and thawed extract of the pellet were interacted with the different bacterial strains, whileStreptococcus faecalis andStaphylococcus aureus released 60% and 75% of the radioactive label, only 38% of it was solubilized fromStreptococcus mutans, following their incubation with the CF supernate. The findings agreed with results obtained by interacting bacteria with a frozen and thawed lysate of human peripheral blood leukocytes. On the other hand, extracts from frozen and thawed CF pellet were inactive. Further, lipoteichoic acid and lipopolysaccharide were released by CF from Gram-positive and Gram-negative bacteria, respectively. The role of bateriolytic factors, present in CF, as a result of the interaction between microorganisms and leukocytes at inflammatory sites is discussed.This work forms a part of the DMD thesis of Gad Natan.     

Involvement of endogenous enkephalins in the mouse 'behavioral despair' test

In the mouse 'behavioral despair' test the immobility time was shortened by [D-Ala2,Met5]enkephalin at doses which did not modify locomotor activity. Similarly, the inhibitors of the enzymes degrading enkephalins, thiorphan and/or bestatin were effective. Their effect was antagonized by naloxone. We conclude that endogenous enkephalins are implicated in the 'behavioral despair' test.     

An immunological and cytogenetic investigation of tuberous sclerosis

Patients with tuberous sclerosis were studied to investigate the pathophysiological basis for hamartoma and neoplasia development in this disease. Chromosome banding, aberration following G-2 x-ray exposure, and the frequency of sister chromatid exchange were normal. Mean IgM levels were significantly elevated above those of random institutionalized control patients but not above cottage-mate controls. Although 4 out of 10 patients did not respond to any of the skin test antigens used, tuberous sclerosis patients and controls had similar responses to in vitro lymphocyte transformation. This study failed to reveal any cytogenetic abnormalities or conclusive evidence of immune deficiency in tuberous sclerosis.     

Acceptability and preliminary feasibility of an internet/CD-ROM-based education and decision program for early-stage prostate cancer patients: randomized pilot study

Background

Prostate cancer is the most common cancer affecting men in the United States. Management options for localized disease exist, yet an evidence-based criterion standard for treatment still has to emerge. Although 5-year survival rates approach 98%, all treatment options carry the possibility for significant side effects, such as erectile dysfunction and urinary incontinence. It is therefore recommended that patients be actively involved in the treatment decision process. We have developed an Internet/CD-ROM-based multimedia Prostate Interactive Educational System (PIES) to enhance patients’ treatment decision making. PIES virtually mirrors a health center to provide patients with information about prostate cancer and its treatment through an intuitive interface, using videos, animations, graphics, and texts.

Objectives

(1) To examine the acceptability and feasibility of the PIES intervention and to report preliminary outcomes of the program in a pilot trial among patients with a new prostate cancer diagnosis, and (2) to explore the potential impact of tailoring PIES treatment information to participants’ information-seeking styles on study outcomes.

Methods

Participants (n = 72) were patients with newly diagnosed localized prostate cancer who had not made a treatment decision. Patients were randomly assigned to 3 experimental conditions: (1) control condition (providing information through standard National Cancer Institute brochures; 26%), and PIES (2) with tailoring (43%) and (3) without tailoring to a patient’s information-seeking style (31%). Questionnaires were administrated before (t1) and immediately after the intervention (t2). Measurements include evaluation and acceptability of the PIES intervention, monitoring/blunting information-seeking style, psychological distress, and decision-related variables (eg, decisional confidence, feeling informed about prostate cancer and treatment, and treatment preference).

Results

The PIES program was well accepted by patients and did not interfere with the clinical routine. About 79% of eligible patients (72/91) completed the pre- and post-PIES intervention assessments. Patients in the PIES groups compared with those in the control condition were significantly more likely to report higher levels of confidence in their treatment choices, higher levels of helpfulness of the information they received in making a treatment decision, and that the information they received was emotionally reassuring. Patients in the PIES groups compared with those in the control condition were significantly less likely to need more information about treatment options, were less anxious about their treatment choices, and thought the information they received was clear (P < .05). Tailoring PIES information to information-seeking style was not related to decision-making variables.

Conclusions

This pilot study confirms that the implementation of PIES within a clinical practice is feasible and acceptable to patients with a recent diagnosis of prostate cancer. PIES improved key decision-making process variables and reduced the emotional impact of a difficult medical decision.