Diurnal and nocturnal drooling in Parkinson’s disease

Drooling as symptom of Parkinson’s disease (PD) has thus far been poorly defined. This uncertainty is reflected by high variations in published prevalence rates. The aim of this study was to investigate the prevalence of saliva loss versus accumulation of saliva as a possible preliminary stage, and diurnal drooling versus nocturnal drooling. In addition, we evaluated the association between drooling severity and the severity of facial and oral motor disorders. We collected age, disease duration, UPDRS III and Hoehn & Yahr stage from 104 consecutive outpatients with PD. Diurnal and nocturnal drooling was evaluated with a validated questionnaire (ROMP-saliva). A speech pathologist, blinded for drooling severity, rated facial expression, involuntary mouth opening and difficulty with nose breathing and also interviewed patients about sleeping position and nose-breathing during the night. Thirty patients (29%) had no complaints with saliva control (‘non-droolers’), 45 patients (43%) experienced accumulation of saliva or only nocturnal drooling (‘pre-droolers’), and 29 (28%) had diurnal drooling (24 of which also drooled during the night; ‘droolers’). The droolers had longer disease duration (10 vs. 7 years, p = 0.01) and drooling was independently associated with involuntary mouth opening (OR = 2.0; 95% CI 1.02–3.99) and swallowing complaints (OR = 1.2; 95% CI 1.03–1.31). Diurnal drooling—defined as dribbling of saliva while awake—is present in about 28% of PD patients. This is less than usually reported. Diurnal drooling typically appeared later in the disease course. The association with oral motor behavior should encourage the development of behavioral treatment approaches

Cytotoxic lymphocytes in B-cell chronic lymphocytic leukemia

The occurrence of cytotoxic lymphocyte subpopulations (i.e., CD 16+, CD57+ and cytotoxic CD 8+) was studied in the peripheral blood of 18 B-cell chronic lymphocytic leukemia (B-CLL) patients. The absolute numbers of CD 57+, CD 16+ and cytotoxic CD 8+ lymphocytes were increased in the peripheral blood of untreated patients as compared with healthy donors, suggesting a causal relation with the accumulation of malignant B-cells. For 5 B-CLL patients and 5 hematological normal donors, the lymphocyte subpopulations in peripheral blood, lymph nodes and bone marrow were determined. A significant immune response was observed in the lymph nodes of the patients, as reflected by the CD 3+ lymphocytes, which were 1.7–27 times larger in the patients lymph nodes than in their peripheral blood and bone marrow. In contrast, with peripheral blood this was mainly caused by an increase in CD 4+ lymphocytes. The CD 57 lymphocytes in the lymph nodes of the patients had abnormal orthogonal light-scattering signals and an abnormal density of CD 57+ receptors in comparison with their peripheral blood CD 57+ lymphocytes or the CD57+ lymphocytes in the peripheral blood, bone marrow and tonsils of the hematological normal donors. This study shows that although a significant increase of cytotoxic lymphocytes in the peripheral blood of B-CLL patients is observed, the actual distributions of the non-malignant lymphocytes can be quite different at the actual tumor sites, i.e., bone marrow and lymph node

Angiotensinogen M235T gene variants and its association with essential hypertension and plasma renin activity in Malaysian subjects: A case control study

BACKGROUND: Essential hypertension is a major public health concern worldwide where its prevalence accounts for various cerebrovascular diseases. A common molecular variant of angiotensinogen (AGT), the precursor of potent vasoactive hormone angiotensin II, has been incriminated as a marker for genetic predisposition to essential hypertension in some ethnics. This case-control study was designed not only to determine the association of the AGT M235T gene variants with essential hypertension, but also its relationship to Plasma Renin Activity (PRA) in subjects attending the Health Clinic, Kuala Lumpur, Malaysia. METHODS: The study involved 188 subjects, 101 hypertensives and 87 normotensives. Consents were obtained from all the participated subjects. M235T gene variants were investigated using allele specific polymerase chain reaction and PRA was determined by radioimmunoassay. Hypertensinogenic factors such as dietary habits, physical activity, smoking and drinking habits were assessed using a pre-tested questionnaire. RESULTS: The genotype and allele distribution of the M235T variant differed significantly in hypertensives and normotensives (χ(2 = )23.184, P < 0.001 and χ(2 )= 21.482, P < 0.001, respectively). The odds ratio for hypertension was 1.36 (95% confidence interval 1.03–1.80) for subjects with homozygous mutated allele TT of the M235T variant compared with other genotypes or 1.98 (95% confidence interval 1.46–2.67) for those carrying T allele compared to those carrying M allele. Plasma Renin Activity is also significantly higher in hypertensive subjects (PRA = 3.8 ± 2.5 ngAI/ml/hr for hypertensives, PRA = 2.6 ± 1.3 ngAI/ml/hr for normotensives, P < 0.001), but was not significantly different between groups of genotypes (P = 0.118). CONCLUSION: The M235T variant of the AGT is significantly associated with essential hypertension whereas the genotype TT or allele T is a possible genetic marker or risk factor for hypertension in Malaysian subjects

Assessment of fall-related self-efficacy and activity avoidance in people with Parkinson's disease

<p>Abstract</p> <p>Background</p> <p>Fear of falling (FOF) is common in Parkinson's disease (PD), and it is considered a vital aspect of comprehensive balance assessment in PD. FOF can be conceptualized differently. The Falls-Efficacy Scale (FES) assesses fall-related self-efficacy, whereas the Survey of Activities and Fear of Falling in the Elderly (SAFFE) assesses activity avoidance due to the risk of falling. This study aimed at investigating the validity and reliability of FES and SAFFE in people with PD.</p> <p>Methods</p> <p>Seventy-nine people with PD (mean age; 64 years, SD 7.2) completed the Swedish version of FES(S), SAFFE and the physical functioning (PF) scale of the 36-Item Short-Form Health Survey (SF-36). FES(S) and SAFFE were administered twice, with an 8.8 (SD 2.3) days interval. Assumptions for summing item scores into total scores were examined and score reliability (Cronbach's alpha and test-retest reliability) were calculated. Construct validity was assessed by examining the pattern of Spearman correlations (r_s) between the FES(S)/SAFFE and other variables, and by examining differences in FES(S)/SAFFE scores between fallers and non-fallers, genders, and between those reporting FOF and unsteadiness while turning.</p> <p>Results</p> <p>For both scales, item mean scores (and standard deviations) were roughly similar and corrected item-total correlations exceeded 0.4. Reliabilities were ≥0.87. FES(S)-scores correlated strongest (r_s, -0.74, p < 0.001) with SAFFE-scores, whereas SAFFE-scores correlated strongest with PF-scores (r_s, -0.76, p < 0.001). Both scales correlated weakest with age (r_s≤ 0.08). Experiencing falls, unsteadiness while turning, and FOF was associated with lower fall-related self-efficacy and higher activity avoidance.</p> <p>Conclusions</p> <p>This study provides initial support for the score reliability and validity of the FES(S) and SAFFE in people with PD.</p

Noisy galvanic vestibular stimulation promotes GABA release in the substantia nigra and improves locomotion in hemiparkinsonian rats

Dopamine related disorders usually respond to dopaminergic drugs, but not all symptoms are equally responsive. In Parkinson’s disease (PD) in particular, axial symptoms resulting in impaired gait and postural control are difficult to treat. Stochastic vestibular stimulation (SVS) has been put forward as a method to improve CNS function in dopamine related disorders, but the mechanisms of action are not well understood. This thesis aimed to investigate the effects of SVS on neuronal brain activity and to evaluate the possible enhancing effect of SVS on motor control in PD and on cognitive functions and motor learning in Attention deficit hyperactivity disorder (ADHD). Behavioural tests were conducted in the 6-OHDA rat model of PD using the accelerating Rotarod and the Montoya skilled reach test to evaluate the effect of SVS on motor control. The effect of SVS on brain activity was assessed using in vivo microdialysis and immunohistochemistry. We evaluated the effect of SVS on postural control and Parkinsonism in patients with PD and the effect of SVS on cognitive function in people with ADHD. The behavioural animal studies indicate that SVS may have an enhancing effect on locomotion, but not skilled forepaw function. SVS increased GABA transmission in the ipsilesional substantia nigra (SN) and may have a rebalancing effect on dysfunctional brain activity. SVS increased c-Fos activity more than levodopa and saline in the vestibular nucleus of all animals. c-Fos expression was also higher in this region in the 6-OHDA lesioned than in shamlesioned animals, supporting the theory that SVS may have larger effects in the dopamine depleted brain. SVS increased c-Fos expression in the habenula nucleus substantially more than levodopa did. Furthermore, SVS and levodopa had similar effects on many brain regions, including the striatum, where saline had no effect. The clinical studies revealed improvement of postural control in PD during SVS. There was a trend towards reduced Parkinsonism during SVS when off levodopa. No substantial effects were found on cognitive performance in ADHD. In PD, SVS may improve motor control by inhibiting the overactive SN, possibly through a non-dopaminergic modulatory pathway involving increased neurotransmission in the habenula nucleus. SVS could be trialled in larger studies to evaluate long-term effects on treatment resistant axial symptoms associated with PD

Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers

Background Epidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties. Objective We used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors. Methods We used individual data for participants of European ancestry from the Courage-PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease; PD, N = 16,519) and EPITHYR (differentiated thyroid cancer, N = 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium; PD, N = 482,730), Melanoma Meta-Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross-phenotypes polygenic risk score (PRS) analyses. Results We confirmed a previously reported positive genetic correlation of PD with melanoma (Gcorr = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (Gcorr = 0.11 [0.03; 0.19]). There was a significant inverse association between the PRS for ovarian cancer and PD (odds ratio [OR] = 0.89 [0.84; 0.94]). Conversely, the PRS of PD was positively associated with breast cancer (OR = 1.08 [1.06; 1.10]) and inversely associated with ovarian cancer (OR = 0.95 [0.91; 0.99]). The association between PD and ovarian cancer was mostly driven by rs183211 located in an intron of the NSF gene (17q21.31). Conclusions We show evidence in favor of a contribution of pleiotropic genes to the association between PD and specific cancers. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA

11-Hydroxyandrostenedione is metabolised to novel androgenic C19 steroids in the prostate

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