Freezing of gait affects quality of life of peoples with Parkinson's disease beyond its relationships with mobility and gait.

The aim of this study was to examine the association between freezing of gait (FOG) and quality of life (QoL) in patients with Parkinson's disease (PD). PD patients (n = 118) completed the PDQ-39 (QoL) and FOG-Q questionnaires. Disease severity was assessed by the Hoehn and Yahr (H&Y) staging and the Unified Parkinson's Disease Rating Scale (UPDRS). The relations between those parameters were assessed using regression models. 66 men and 52 women (mean age 65.8 +/- 10.2 years, UPDRS total score 48.4 +/- 17.1, disease duration 8.5 +/- 5.8 years, H&Y stage 2.7 +/- 0.8) participated. FOG severity had a significant effect on QoL (P < 0.0015), accounting for disease severity assessed by UPDRS. Specifically, FOG severity was correlated with all the dimensions of the PDQ-39 except for stigma and social support, as follows: with mobility, bodily discomfort, activity of daily living (ADL) (P < 0.005 in all), with emotional, communication, and cognition (P < 0.05 in all). FOG severity (FOG-Q) was also found to affect a modified PDQ total score, without the mobility aspect (P = 0.0081). FOG should be viewed as a highly important symptom with regard to QoL of PD patients beyond its effect on gait and mobility. On the basis of the present results, special attention should be given to FOG in the treatment of patients with PD.     

Phialemonium curvatum arthritis of the knee following intra-articular injection of a corticosteroid.

Phialemonium curvatum arthritis of the knee developed in a diabetic man following intra-articular injection of a corticosteroid. Cure was achieved with a 6-week course of intravenous amphotericin B deoxycholate. P.curvatum is commonly found in the environment and is often considered a contaminant; yet, its pathogenic potential should be seriously considered in selected patients.     

The mutation spectrum of hyperphenylalaninaemia in the Republic of Ireland: the population history of the Irish revisited

Phenylketonuric and hyperphenylalaninaemic patients in the population of the Republic of Ireland were screened for mutations at the human phenylalanine hydroxylase (PAH) locus. A composite data set for the island of Ireland was generated by merging the findings of this study with extant data for Northern Ireland. Analysis of this data on the basis of the four historic provinces (Munster, Leinster, Connacht and Ulster) revealed genetic diversity that is informative in terms of demographic forces that shaped the Irish population. R408W, the predominant Irish PAH mutation associated with haplotype 1.8, reached its highest relative frequency in the most westerly province, Connacht. This suggests that the gradient of R408W-1.8 observed across north-western Europe continues into Ireland and peaks in Connacht. Spatial autocorrelation analysis demonstrated that the gradient is consistent with a localised cline of R408W-1.8 likely to have been established by human migration. This and parallel allele frequency clines may represent the genetic traces of the Palaeolithic colonisation of Europe, a pattern not substantially altered in north-western Europe by subsequent Neolithic migrations. An analysis of mutant allele distributions in Ulster, Scotland and the rest of Ireland confirmed that Ulster has been a zone of considerable admixture between the Irish and Scottish populations, indicating a proportion of Scottish admixture in Ulster approaching 46%. Mutations primarily associated with Scandinavia accounted for 6.1% of mutations overall, illustrating the influence of Viking incursions on Irish population history.     

The additive miotic effects of dapiprazole and pilocarpine

Background: Since dapiprazole on alpha-adrenergic agent, produces miosis by paralyzing the dilator muscle, and pilocarpine, a parasympathetic drug, causes miosis by affecting the sphincter, we speculated that the two drugs might have additive effects. Methods: The additive miotic actions of pilocarpine 2% and dapiprazole 0.5% were evaluated by comparing the effects of two drugs given together and alone on the reversal of mydriasis induced by tropicamide (0.5%) and phenylephrine (10%) in one eye each of 60 healthy volunteers. Results: Dapiprazole and pilocarpine together induced miosis significantly faster than each drug alone, showing additive effects. Conclusion: Co-administration of dapiprazole and pilocarpine at the end of the eye examination will induce fast pupillary constriction, which might be useful in preventing the development of an acute attack of angle-closure glaucoma in patients with anatomically narrow angles.     

Statin Therapy for Primary Prevention in the Elderly and Its Association with New-Onset Diabetes,Cardiovascular Events,and All-Cause Mortality

PurposeThis study assessed associations of the use of statins for primary prevention with cardiovascular outcomes among adults ages ≥70 years.MethodsIn a retrospective population-based cohort study, new users of statins without cardiovascular disease or diabetes mellitus were stratified by ages ≥70 years and <70 years. Using a time-dependent approach, adherence to statins was evaluated according to the proportion of days covered: <25%, 25%-50%, 50%-75%, and ≥75%. We assessed associations of statin therapy with increased risk of new-onset diabetes mellitus and with decreased risks of major adverse cardiovascular events and all-cause mortality.ResultsOf 42,767 new users of statins, 5970 (14%) were ages ≥70 years. The incident rates of major adverse cardiovascular events, all-cause mortality, and new-onset diabetes mellitus in the highest to lowest proportion of days covered categories were 16.9%, 16.7%, and 9.4% and 6.3%, 1.7%, and 9.4%, respectively. For the older group, the adjusted hazard ratios of major adverse cardiovascular events and mortality were significantly decreased for the highest adherence group (proportion of days covered ≥75%): 0.71 (0.57-0.88) and 0.68 (0.54-0.84), respectively. The respective hazard ratios were less favorable for the younger group: 0.80 (0.68-0.93) and 0.74 (0.58-1.03). The risk of new-onset diabetes mellitus was increased for the younger but not the older group.ConclusionsStatin use for primary prevention was associated with cardiovascular benefit in adults ages ≥70 years without a significant risk for the development of diabetes. These data may support the use of statin therapy for primary prevention in the elderly.     

Prolonged patients’ In-Hospital Waiting Period after discharge eligibility is associated with increased risk of infection,morbidity and mortality: a retrospective cohort analysis

Background

Prolonged, inappropriate hospital stay after patients’ eligibility for discharge from internal medicine departments is a world-wide health-care systems’ problem. Nevertheless, the extent to which such surplus hospital stays are associated with infectious complications, their time frame of appearance and their long-term implications was not previously addressed.

Methods

We conducted a retrospective cohort analysis of patients experiencing an In-hospital Waiting Period (IHWP) after discharge eligibility in a single, tertiary hospital.

Results

We screened the records of 245 patients out of which 104 patients fulfilled our inclusion criteria. The mean length of IHWP was 15.7?±?4.79 day during which 9(8.7 %) patients died. The study primary composite end-point, in-hospital mortality or hospital acquired infection (pneumonia, UTI or sepsis) occurred in 32(31 %) patients. The most hazardous time was during the first 3 IHWP days: 63.7 % of patients experienced a complication and 44 % of the total complications occurred during this period. The occurrence of any complication during IHWP was associated, with statistical significance, with increased risk of mortality during the first year after IHWP initiation (HR?=?6.02, p?=?0.014).

Conclusion

Prolongation of hospital stay after patients are deemed to be discharged from internal medicine departments is associated with increased morbidity and mortality, mainly during the first surplus days of in-hospital stay. Efforts should be made to shorten such hospital stays as much as possible.

     

The importance of timing in melatonin administration in a blind man

An 18-year-old blind man suffered from chronic sleep disturbances associated with daytime fatigue and excessive daytime somnolence. After two unsuccessful treatment regimens with 5 mg and 10 mg melatonin administered at bedtime (2200-2230), a third regimen of 5 mg melatonin administered at 2000 for 3 weeks resulted in a successful resolution of his sleep disturbances. We suggest that the efficacy of melatonin in ameliorating sleep disturbances because of alterations in circadian rhythmicity may be dependent on the time of administration.     

The Involvement of Collagen Triple Helix Repeat Containing 1 in Muscular Dystrophies

Apolipoprotein E4 (APOE4) genotype is the strongest genetic risk factor for late-onset Alzheimer disease and confers a proinflammatory, neurotoxic phenotype to microglia. Here, we tested the hypothesis that bone marrow cell APOE genotype modulates pathological progression in experimental Alzheimer disease. We performed bone marrow transplants (BMT) from green fluorescent protein–expressing human APOE3/3 or APOE4/4 donor mice into lethally irradiated 5-month-old APPswe/PS1ΔE9 mice. Eight months later, APOE4/4 BMT–recipient APPswe/PS1ΔE9 mice had significantly impaired spatial working memory and increased detergent-soluble and plaque Aβ compared with APOE3/3 BMT–recipient APPswe/PS1ΔE9 mice. BMT-derived microglia engraftment was significantly reduced in APOE4/4 recipients, who also had correspondingly less cerebral apoE. Gene expression analysis in cerebral cortex of APOE3/3 BMT recipients showed reduced expression of tumor necrosis factor-α and macrophage migration inhibitory factor (both neurotoxic cytokines) and elevated immunomodulatory IL-10 expression in APOE3/3 recipients compared with those that received APOE4/4 bone marrow. This was not due to detectable APOE-specific differences in expression of microglial major histocompatibility complex class II, C-C chemokine receptor (CCR) type 1, CCR2, CX3C chemokine receptor 1 (CX3CR1), or C5a anaphylatoxin chemotactic receptor (C5aR). Together, these findings suggest that BMT-derived APOE3-expressing cells are superior to those that express APOE4 in their ability to mitigate the behavioral and neuropathological changes in experimental Alzheimer disease.Humans uniquely have three different apolipoprotein E (APOE) alleles (ɛ2, ɛ3, and ɛ4). APOE4 is the single greatest genetic risk factor for late-onset Alzheimer disease (AD), and there is a gene dosage effect.¹ However, genetic association does not inform function/pathogenesis. Multiple mechanisms have been postulated that predominantly focus on production, metabolism, or clearance of amyloid-β (Aβ) and that are variably supported by multiple observations, including: i) APOE genotype is strongly related to Aβ levels in brain and cerebrospinal fluid of AD patients^2,3; ii) modulation of apolipoprotein E (apoE) protein levels in brain results in alterations of Aβ burden^4,5; iii) Aβ degradation is at least partially apoE dependent^6,7; and iv) Aβ clearance is differentially modulated by apoE isoforms, with APOE4 mice exhibiting reduced central and peripheral Aβ clearance compared with APOE3 mice.^8–10 Aβ degradation and clearance is at least partially dependent on microglia, the innate immune effector cells of the brain. Microglia have migratory and phagocytic capacity, are increased in the vicinity of Aβ plaques, and phagocytose Aβ.^11–13 APOE genotype modulates central nervous system innate immune function in culture,¹⁴ including astrocyte and microglia elaboration of cytokines and chemokines,^15,16 microglia production of reactive oxygen species,¹⁷ microglia-mediated paracrine neurotoxicity,¹⁸ microglia migration,¹⁹ and other functions.²⁰ However, the specific contribution of microglial APOE genotype to AD pathophysiology in vivo is largely unknown.To address this critical question and to test a potential therapeutic application, we used the fact that bone marrow transplantation (BMT) results in the gradual replacement of endogenous (host) microglia (to the near exclusion of other cell types) with microglia derived from donor marrow, in both wild-type mice and transgenic mouse models of AD.^21–24 We used targeted-replacement (TR) APOE mice homozygous for either the APOE3 or APOE4 gene inserted into the mouse APOE regulatory elements^25,26 that coexpressed green fluorescent protein (GFP). We transplanted whole bone marrow (BM) isolated from TR APOE3/3;GFP or TR APOE4/4;GFP mice into lethally irradiated APPswe/PS1ΔE9 mice to determine the specific role of microglial APOE genotype in the pathological progression of AD.