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Au and Pd atoms adsorbed on pure and Ti-doped SiO2/Mo(112) films.

The interaction of Pd and Au atoms with a silica surface and SiO2Mo(112) ultrathin films has been studied with periodic density-functional theory-generalized gradient approximation calculations. On both unsupported and supported silica, Pd and Au are weakly bound. No charge transfer occurs to the empty Pd and Au orbitals. Differently from Au, Pd can easily penetrate with virtually no barrier into the hexagonal rings of the supported silica film and binds strongly at the SiO2-Mo interface. The same process for Au implies overcoming a barrier of 0.9 eV. Completely different is the behavior of Ti-doped silica films. Au forms a direct covalent bond with substitutional Ti at the expense of the Ti...O-Mo interface bond which breaks. The global process is exothermic by 1 eV and nonactivated, showing that Ti doping results in solid anchoring points for the adsorbed Au atoms and for nucleation and growth of small gold particles. The effect of Ti doping is less pronounced for Pd but still visible with substantial enhancement of the Pd adsorption strength.

Journal Article↗

Three-year analysis of microbial aetiology and antimicrobial susceptibilities of PD peritonitis.

The first-line antibiotic treatment of peritoneal dialysis (PD) peritonitis has to cover the most common causative microorganisms. Our aim was to analyse antimicrobial sensitivities of different empirical protocols for initial therapy of PD peritonitis. We analysed the aetiological microorganisms of PD peritonitis and their antimicrobial sensitivities during a 36-month period. Clinical characteristics of the cases were recorded. Altogether 86 PD peritonitides were diagnosed during the study period. In 58 cases, microbial cultures were positive with 72 different causative agents. 28 cases (33%) were culture-negative. Over-representation of icodextrin users was noted among the culture-negative cases. Staphylococcus aureus was the most frequent causative agent, often leading to severe course of illness. Of antimicrobial protocols for initial treatment of peritonitis tested in vitro, the combination of a first-generation cephalosporin and an aminoglycoside was superior to the combination of a first-generation cephalosporin and ceftazidime as well as to fluoroquinolone monotherapy but similar to the combination of vancomycin and ceftazidime. Based on antimicrobial sensitivities we continue using an aminoglycoside in the empirical treatment of PD peritonitis. In the present material, users of icodextrin PD fluid were over-represented among patients with culture-negative peritonitis.

Aged↗

Cloning and identification of two novel splice variants of human PD-L2.

PD-L2, a newly identified member of B7 family, plays a role in down-regulating T cell responses. The common PD-L2 mRNA (type I) is the splicing product containing all 6 exons. We report here the identification of two human PD-L2 splice variants in activated leukocytes. One splice variant (type II) is generated through splicing out exon 3 encoding Ig constant-like domain; it retains all other regions without a frame shift. The other variant (type III) is created by splicing out exon 3 to an alternative acceptor site 5 bp downstream of the canonical acceptor site, leading to a frame shift. Consequently, the translated protein should be a soluble form. Furthermore, type I isoform is expressed on the plasma surface whereas type II isoform showed a pattern of intracellular membrane distribution in the transiently transfected K562 cells. In addition, the expression patterns of PD-L2 splice variants are variable in different individuals and distinct cellular status. These results suggest that PD-L2 expression may be controlled by posttranscriptional regulation through alternative splicing, and modulation of PD-L2 isoform expression may influence the outcome of immune response.

Alternative Splicing↗

Cognitive assessment of a representative community population with Parkinson's disease (PD) using the Cambridge Cognitive Assessment-Revised (CAMCOG-R).

BACKGROUND: cognitive decline is well recognised in Parkinson's disease (PD) but the best cognitive assessment tool for use in such patients remains unclear. The 30-point Mini-Mental State Examination (MMSE), while quick and straightforward to use, fails to cover a full range of cognitive domains and is recognised to have a ceiling effect. The Cambridge Cognitive Assessment-Revised (CAMCOG-R) is a cognitive screening tool allowing the assessment of a number of different domains of cognition. It has not previously been used specifically on PD subjects. METHODS: a prevalent community population of 135 PD patients were assessed cognitively using the MMSE. Those scoring 25 or above on the MMSE were subsequently further assessed using CAMCOG-R. Demographic and disease factors including disease duration, symptom severity, anxiety, depression and the presence of hallucinations were recorded for each participant. RESULTS: 31/135 (23%) demonstrated cognitive impairment on the MMSE (score < 25). Ninety-four of the remaining group (10 were excluded) achieved a median total CAMCOG-R score of 89/104. The results were widely distributed. The subjects scored particularly highly in the cognitive domains of orientation, comprehension and perception but relatively poorly at memory and abstract thinking. Significantly poorer scores (P < 0.05) were seen throughout the cognitive domains with increasing age, increasing PD symptom severity and increasing disease duration, but not with the presence of anxiety, depression or hallucinations in the subjects. DISCUSSION: CAMCOG-R was found to be a viable and useful cognitive screening tool for use in PD. A wide range of cognitive ability was demonstrated in subjects who had been assessed previously by the MMSE as not having significant cognitive impairment. The group performed worse in certain cognitive domains than others and those who were older, with more severe PD symptoms and with symptoms for longer, scored less well.

Aged↗

In-vitro susceptibilities of Pseudomonas aeruginosa and Pseudomonas spp. to the new fluoroquinolones clinafloxacin and PD 131628 and nine other antimicrobial agents.

The in-vitro activities of two new fluoroquinolones, clinafloxacin (CI-960, PD 127391, AM-1091) and PD 131628 (the active component of the pro-drug CI-990, PD 131112) and nine other antibiotics were tested against 107 clinical isolates of Pseudomonas aeruginosa, 12 isolates of Xanthomonas maltophilia, and 19 isolates of other Pseudomonas spp. Of the 107 P. aeruginosa isolates, 33 were resistant to gentamicin, tobramycin and amikacin, 17 were resistant to only one or two of these aminoglycosides and 24 were aminoglycoside sensitive. Thirty-three were isolates from cystic fibrosis patients. Susceptibility studies were performed using the agar dilution technique and kinetic time kill curves. With the exception of aminoglycoside-sensitive P. aeruginosa isolates where ciprofloxacin had similar activity to clinafloxacin and PD 131628, the two new fluoroquinolones were the most active agents against all isolates tested (MIC90 0.25-2.0 mg/L). Cross-resistance was identified with ciprofloxacin and ofloxacin-resistant strains, but the superior activity of clinafloxacin and PD 131628 resulted in 90% of the isolates having MICs < 2 mg/L. Kinetic kill curves with aminoglycoside-sensitive P. aeruginosa revealed ciprofloxacin to have the most rapid and sustained killing. However, with amino-glycoside-resistant P. aeruginosa isolates, clinafloxacin and PD 131628 were more rapidly bactericidal than ciprofloxacin.

Anti-Infective Agents↗

Antibacterial activity of PD 131628 and proposed disc diffusion susceptibility test criteria.

The antibacterial activity of PD 131628 was compared with that of ciprofloxacin against 401 clinical isolates. The two drugs had comparable MICs for most Gram-negative species. PD 131628 was two to eight times more active against Gram-positive species and against Xanthomonas maltophilia. Both drugs were bactericidal, Among Gram-positive isolates, resistant mutants were not detected in vitro. Among Gram-negative bacilli, spontaneously occurring mutants resistant to PD 131628 were readily demonstrated more frequently than for ciprofloxacin. Resistance to PD 131628 was more readily induced by serially transferring the Gram-negative species, and resistant organisms emerged more rapidly on prolonged incubation in time-kill studies. Correlating the PD 131628 5 micrograms disc diffusion zone diameters with PD 131628 MICs, the following breakpoints are tentatively proposed: susceptible, MIC < or = 1 mg/L or zone > or = 19 mm; intermediate, MIC 2.0 mg/L or zones 16-18 mm; and resistant, MIC > or = 4.0 mg/L or zones < or = 15 mm.

Anti-Infective Agents↗

Sperm selection by PD-10 sephadex columns: comparison with SpermPrep filtration and Percoll centrifugation.

The efficacy of a disposable, prepacked column (PD-10) containing Sephadex G-25, to select motile spermatozoa, was compared with another column for sperm filtration (SpermPrep) and centrifugation through Percoll gradients. Aliquots of washed sperm suspensions were processed by the three techniques. The number of motile cells and the proportion of total spermatozoa selected was similar for all methods. Recovery of spermatozoa showing optimal movement was 145.9 +/- 30% (mean +/- SEM) with PD-10 columns and 131.9 +/- 32% with Percoll, both significantly higher than SpermPrep (71.9 +/- 11%; P < 0.05). The straight line velocity of motile cells was lower in samples processed by SpermPrep (29.3 +/- 2 microns/S) compared to both PD-10 (34.7 +/- 1 micron/s) and Percoll (34.9 +/- 2 microns/s; P = 0.07). When whole semen was processed, total sperm recovery with PD-10 was 61.7 +/- 8% versus 47.7 +/- 7% with Percoll (P < 0.001). Percoll centrifugation improved the percentage of morphologically normal spermatozoa more than PD-10. Similar proportions of motile spermatozoa and cells with optimal motility were obtained by both methods. We conclude that PD-10 filtration columns can be used to prepare semen in the laboratory as a practical alternative to other methods.

Cell Separation↗

I-125 versus Pd-103 for low-risk prostate cancer: long-term morbidity outcomes from a prospective randomized multicenter controlled trial.

BACKGROUND: We tested the hypothesis that the shorter half-life of Pd-103 versus I-125 results in different late radiation-related morbidities following prostate brachytherapy. METHODS: As of June 14th, 2002, 352 of a planned total of 600 patients with 1997 American Joint Committee on Cancer (AJCC) clinical stage T1c-T2a prostatic carcinoma (Gleason grade 2-6, PSA 4-10 ng/mL) had been randomized to implantation with I-125 (144 Gy, TG-43) or Pd-103 (125 Gy, NIST-99). Treatment-related morbidity was monitored by questionnaires based on standard American Urologic Association (AUA) and Radiation Therapy Oncology Group (RTOG) criteria that were mailed at 1, 3, 6, 12, 18, and 24 months after implant. The use of alpha-blockers to relieve obstructive symptoms was not controlled for but was noted at each follow-up point. All patients reported here had a minimum follow-up of 2 years. Dosimetric parameters analyzed included the V100, which was defined as the percentage of the postimplant prostate volume covered by 100% of the prescription dose. Rectal doses were expressed as the R100, defined as the rectal volume (cc) that received at least 100% of the prescription dose. Statistical comparisons were by Student's unpaired t-test at specified follow-up times. RESULTS: The AUA scores peaked at the 1-month postimplant time point for both isotopes and gradually declined. The difference in AUA scores between patients who received I-125 versus those who received Pd-103 was greatest at 1 and 6 months following implantation. At 1 month, I-125 patients had a mean AUA score of 14.8 (+/-9.5) compared with 18.6 (+/-9.8) for the Pd-103 patients (P = 0.0009). By 6 months, mean AUA scores for the I-125 patients had decreased to 12.0 (+/-9.1) compared with 9.9 (+/-8.7) for the Pd-103 patients (P = 0.04). The use of alpha-blockers was similar between groups at all time points. Radiation proctitis (persistent bleeding) occurred in 29 of 314 patients (9%). There was an overall trend toward more proctitis in I-125 patients (P = 0.21). However, only four of the 163 patients (2%) with an R100 below the recommended 1.0 cc developed bleeding, which did not differ between isotopes (P = 0.49). DISCUSSION: Patients treated with Pd-103 had more intense radiation prostatitis in the first month after implantation, but they recovered from their radiation-related symptoms sooner than I-125 patients, consistent with palladium's shorter half-life. The trend toward more proctitis in the I-125 patient group likely reflects their higher R100 values due to less rapid dose fall-off that can be overcome with judicious treatment planning and implant execution.

Aged↗

Pharmacokinetic-pharmacodynamic (PK-PD) modelling in non-steady-state studies and arterio-venous drug concentration differences.

In conducting a non-steady-state pharmacokinetic (PK)-pharmacodynamic (PD) study there is potential for the observed effect (E) vs time, and venous plasma drug concentration (C) vs time, profiles to display temporal displacement with respect to each other. This is most frequently observed when there exists a distributional nonequilibrium across the effect organ giving rise to hysteresis, i.e. observed C preceding E in the time domain, with the resulting potential for a counterclockwise loop to be generated in the observed E vs C plot (when data are connected in time-order). Such temporal displacement does not afford direct prediction of the steady-state E vs C PD relationship. When an arterio-venous (A-V) difference exists across the tissues of the blood sampling compartment (i.e. the arm), and this arises solely from an elimination process then drug concentration in the respective peripheral arterial plasma and venous plasma compartments will be in equilibrium at all times during a non-steady-state PK experiment. If there are no other sources of temporal displacement in the relationship between E and C then the observed E vs C plot will be a direct predictor of the steady-state E vs C PD relationship. In contrast when the A-V difference is of a distributional nature then proteresis, i.e. observed E preceding C in the time domain, will arise with the potential for the generation of a clockwise loop in the observed E vs C relationship. Simulated error-incorporated E vs time, and C vs time, data was analysed by semi-parametric implementation of an effect-compartment link-model that affords accurate steady-state E vs C PD predictions (without the requirement of sampling arterial blood) from data that incorporates the concurrent presence of: (i) distributional nonequilibrium across the effect organ, and (ii) distributional A-V non-equilibrium. Accurate steady-state E vs C PD predictions were achieved irrespective of the comparative magnitudes of the two nonequilibria, i.e. whether the rate of equilibration across the effect organ was faster than, or slower than, the rate of equilibration across the arm (resulting in a clockwise or counterclockwise loop in the observed E vs C plot, respectively), or indeed if one or other of the nonequilibria is essentially absent. When the rate of equilibration across the effect organ is slower than the rate of A-V equilibration (i.e. counterclockwise loop generated in the observed E vs C plot) then the need to model for the underlying A-V nonequilibrium is redundant, i.e. accurate steady-state E vs C PD predictions can be achieved with implementation (strictly incorrectly) of a more simple link parameterised solely to model for distributional nonequilibrium across the effect organ.(ABSTRACT TRUNCATED AT 400 WORDS)

Computer Simulation↗

Inhibition of morphine withdrawal by the association of RB 101, an inhibitor of enkephalin catabolism, and the CCKB antagonist PD-134,308.

1. The effects induced in rats on naloxone-precipitated morphine withdrawal syndrome by the new mixed inhibitor of enkephalin catabolism able to cross the blood-brain barrier RB 101 (N-((R,S)-2-benzyl-3[(S)(2-amino-4-methylthio)butyl dithio]-1-ox-opropyl-L-phenylalanine benzyl ester) given alone or associated with the selective CCKB antagonist, PD-134,308, were investigated. 2. The systemic administration of RB 101 (5, 10 and 20 mg kg-1, i.v.) elicited a significant decrease in 8 of the 14 withdrawal signs evaluated. PD-134,308 (3 mg kg-1, i.p.) did not modify the expression of morphine abstinence when given alone, but induced a strong facilitation of RB 101 responses (12 of 14 withdrawal signs were decreased). This potentiation was particularly intense in peripherally mediated withdrawal signs. 3. In order to clarify the biochemical mechanisms implicated in these responses, the effects induced by the association of RB 101 and PD-134,308 on the occupation of brain opioid receptors by endogenous enkephalins were also investigated in mice. PD-134,308, as well as RB 101, inhibited [3H]-diprenorphine binding to opioid receptors. These results suggest that an increase in endogenous enkephalin levels induced by PD-134,308 could participate in the facilitation of RB 101 behavioural responses. 4. RB 101 has a promising potential role in the management of the opiate withdrawal syndrome. CCKB antagonists, such as PD-134,308 may be useful in potentiating this anti-withdrawal effect.

Analgesics↗

The prevalence of PD in a nutritionally deficient rural population in China.

OBJECTIVES: In most reports, the prevalence of PD in mainland China is lower than in western populations. To estimate PD prevalence in China, we performed a cross-sectional study in a rural population in Linxian County, China. PRIMARY OUTCOMES: Clinical diagnosis of PD. RESULTS: Among the 16,488 participants examined, the overall age- and gender-adjusted prevalence rate of PD was 522/100,000 (95% CI: 477-567) assuming no cases of PD would be found among those younger than 50 years of age. The gender-adjusted prevalence rates were 103 (95% CI: 83-123), 621 (95% CI: 572-670), 902 (95% CI: 843-961), and 1744 (95% CI: 1662-1826) per 100,000 in age groups 50-59, 60-69, 70-79, and 80 and above, respectively. CONCLUSIONS: The estimated prevalence of PD in Linxian, China is higher than most of those reported from other areas in China, and similar to those reported from non-Asian populations.

Age Distribution↗

N- and 6-O-sulfated heparan sulfates mediate internalization of coxsackievirus B3 variant PD into CHO-K1 cells.

Recently, it was demonstrated that the coxsackievirus B3 variant PD (CVB3 PD) is able to infect coxsackievirus-adenovirus receptor (CAR)-lacking cells by using heparan sulfates (HS) as additional receptors (A. E. Zautner, U. Korner, A. Henke, C. Badorff, and M. Schmidtke, J. Virol. 77:10071-10077, 2003). For this study, competition experiments with growth factors binding to known HS sequences as well as with specifically desulfated heparins were performed with Chinese hamster ovary cells (CHO-K1) to determine the structural requirements of HS for interaction with CVB3. Hepatocyte growth factor interacting with HS sequences containing [IdUA-GlcNSO(3)(6OSO(3))](n), but not basic fibroblast growth factor binding to [HexUA-GlcNSO(3)-HexUA-GlcNSO(3)-IdUA(2OSO(3))](n), was shown to compete effectively with CVB3 PD for cell surface HS. Whereas unmodified heparin and 2-O-desulfated heparin strongly inhibited the CVB3 PD-induced cytopathic effect, the antiviral activity was markedly reduced after N-, O- and 6-O-desulfation of heparin. Taken together, these results indicate that 6-O- and N-sulfation of GlcNAc of HS is crucial for HS interaction with CVB3 PD and that the disaccharide [IdUA-GlcNSO(3)(6OSO(3))](n) is involved in viral binding. Results from experiments with various inhibitors of endocytic pathways suggest that HS-mediated virus internalization is pH dependent. Despite the fact that CVB3 PD initiates infection about four times slower by making use of HS as a receptor than by using CAR, the time required for a complete viral life cycle in Chinese hamster ovary cells was independent of the utilized receptor.

Animals↗

Cardiac functional responses to adenosine by PD 81,723, an allosteric enhancer of the adenosine A1 receptor.

Adenosine, a locally released and rapidly metabolized nucleoside, protects the heart from damage during ischemia by reducing oxygen demand and increasing oxygen supply. The aminothiophene derivative (2-amino-4,5-dimethylthien-3-yl)[3-(trifluoromethyl)phenyl]-met hanone (PD 81,723) has been shown to act as an allosteric enhancer of the adenosine A1 receptor in brain membranes and thyroid cells. The present study investigates the effects of PD 81,723 in spontaneously contracting right atria and electrically stimulated left atria isolated from Sprague-Dawley rats. N6-cyclopentyladenosine (CPA), an adenosine A1 receptor agonist, produced concentration-dependent inhibition of heart rate in right atria and contractile parameters in left atria. In the right atrium, 5 microM of PD 81,723 significantly shifted the concentration-response curves for CPA to the left, both in the absence and presence of a nonselective adenosine receptor antagonist, 8-(p-sulfophenyl)theophylline (8-SPT, 10 microM). In the left atrium, PD 81,723 also shifted the concentration-response curves for CPA to the left, but only in the presence of 8-SPT. Potentiation of CPA-induced negative chronotropic and inotropic responses with PD 81,723, although not significant, was also observed in the presence of a selective adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 1 nM). These results demonstrate that PD 81,723 enhances the direct negative chronotropic and inotropic effects of adenosine A1 receptor activation in rat atria.

Adenosine↗

Effects of amiloride on alveolar epithelial PD and fluid composition in rabbits.

To look for evidence of active absorption of Na+ in the alveolus in vivo in air-filled lungs, we measured [K+] and [Cl-] in the alveolar lining fluid and the potential difference (PD) across the alveolar epithelium by puncturing alveoli in lungs of anesthetized rabbits with nonselective and ion-selective microelectrodes. After intravenous doses of amiloride, the PD and [K+] decreased (-1.0 +/- 0.3 to -0.3 +/- 0.1 mV, 7.4 +/- 1.1 to 4.2 +/- 0.4 meq/l, P less than 0.001), but [Cl-] did not change (96 +/- 9, 94 +/- 4 meq/l). In another set of experiments, the PD was measured with microelectrodes filled with an electrolyte solution, and midway through each measurement some of the solution was injected into the alveolar lumen. Injecting the solution without amiloride did not alter the alveolar PD (-1.0 +/- 0.4 before and -1.1 +/- 0.5 after injection). The alveolar PD decreased to -0.1 +/- 0.2 mV after injecting the solution with 10(-5) M amiloride into the alveolar interior. These results support the hypothesis that alveolar epithelium in air-filled lungs actively absorbs sodium in vivo, which accounts for the majority of the transepithelial PD.

Amiloride↗

A new home based bioimpedance system for PD.

Fluid overload and uncontrolled hypertension may be considered important mortality risk factors in peritoneal dialysis (PD) population. Even malnutrition is highly prevalent in PD patients. It is now well established that lower levels of serum markers of nutrition such as albumin, creatinine, and prealbumin are associated with increased mortality in PD patients [Fein, P.A. et al: Adv Perit Dial 2002;18:195-199]. Moreover cardiovascular disease is a leading cause of death in patients with end-stage renal disease, and hypertension and volume expansion are highly prevalent in long-term PD patients. Many studies in hemodialysis and in PD have demonstrated that phase sensitive bioelectrical impedance analysis is a widely used and proven method for evaluating patient's body composition. The vectorial bioimpedance analysis is a validated system to evaluate the hydration and nutritional state of hemodialysis and PD patients with acceptable sensitivity and specificity. The aim of this study is to evaluate the reliability and accuracy of the new multifrequency BodyComp bioimpedance analyzer as a home based tool versus traditional Bia Vector.

Adult↗

Enhancement of brain activation during trial-and-error sequence learning in early PD.

BACKGROUND: Although the pathophysiology remains unknown, most nondemented patients with PD have difficulty with frontal tasks, including trial-and-error sequence learning. If given time, they can perform cognitive tasks of moderate difficulty as well as controls. However, it is not known how brain function is altered during this time period to preserve higher cortical function in the face of PD pathology. METHOD: To evaluate this phenomenon, the authors matched sequence learning between PD and control subjects for the last 30 seconds of a PET scan. Learning during the initial 50 seconds of PET was unconstrained. RESULTS: Learning indices were equivalent between groups during the last 30 seconds of the scan, whereas rates of acquisition, correct movements, and forgetting differed in the first 30 seconds. In normal controls sequence learning was associated with activations in the right prefrontal, premotor, parietal, rostral supplementary motor area, and precuneus regions. To achieve equal performance, the PD group activated greater volume within these same regions, and also their left sided cortical homologs and the lateral cerebellum bilaterally. CONCLUSIONS: Mildly affected patients with PD demonstrated only modest impairment of learning during the first 30 seconds of the task and performed equivalently with controls thereafter. However, the mechanism by which they achieved equiperformance involved considerable changes in brain function. The PD group had to activate four times as much neural tissue as the controls, including recruiting brain from homologous cortical regions and bilateral lateral cerebellum.

Aged↗

Diffusion-weighted imaging discriminates progressive supranuclear palsy from PD, but not from the parkinson variant of multiple system atrophy.

BACKGROUND AND OBJECTIVE: The parkinson variant of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP) present with atypical parkinsonism, which may be misdiagnosed as PD, particularly in early disease stages. It was previously shown that diffusion-weighted MRI (DWI) is a sensitive tool to discriminate MSA-P from PD based on increased apparent diffusion coefficients (ADCs) in the putamen. In this study DWI was evaluated in 10 patients with PSP compared with 13 patients with PD and 12 with MSA-P. METHODS: Disease was diagnosed according to established diagnostic criteria and groups were matched for age, disease duration, and Hoehn and Yahr "off" stage. Regional ADCs (rADCs) were determined in different brain regions including basal ganglia, gray matter, white matter, substantia nigra, and pons. RESULTS: In patients with PSP compared with those with PD, rADCs were significantly increased in putamen, globus pallidus, and caudate nucleus. Stepwise logistic regression analysis followed by receiver operating characteristics analysis identified an optimal cut-off value for putaminal rADC, discriminating PSP and PD with a sensitivity of 90% and a positive predictive value of 100%. DWI failed to discriminate PSP and MSA-P. CONCLUSIONS: These results show that DWI detects basal ganglia abnormalities in PSP patients within few years of disease onset, discriminating patients with PSP from those with PD, but not from those with MSA-P.

Aged↗

Validity of family history data on PD: evidence for a family information bias.

OBJECTIVE: To study the validity of information provided by case and control subjects (or their proxies) about PD among their first-degree relatives. METHODS: Secondary cases of PD were assessed both through a single informant (family history method) and through the study of each relative (family study method). The family study method was considered as the standard for comparison, and the sensitivity and specificity of the family history method were studied. RESULTS: A total of 133 population-based case subjects and their 655 relatives were recruited, and 119 population-based control subjects and their 511 relatives. Sensitivity was 68% (95% CI = 47 to 85) for cases and 45% (95% CI = 17 to 77) for controls. Specificity was 99% (95% CI = 98 to 99) for cases and 100% (95% CI = 99 to 100) for controls. The odds ratio (OR) for family history of PD was 4.34 (95% CI = 1.63 to 11.58, p = 0.003) using the family history method and 1.86 (95% CI = 0.78 to 4.44, p = 0.16) using the family study method. The former significant OR more than doubled the latter not significant OR (relative bias = 133%). Bias was more pronounced for proxy interviews and for women informants, and when the relatives were siblings, were living, and were examined or had medical record documentation. CONCLUSIONS: Case subjects with PD (or their proxies) are more aware of PD among their first-degree relatives than control subjects (or their proxies); however, they overreport PD in relatives who are not affected. This causes a substantial family information bias.

Adult↗