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Characteristics of idiopathic REM sleep behavior disorder and that associated with MSA and PD.

OBJECTIVE: To compare the clinical and video-polysomnographic (VPSG) characteristics of idiopathic REM sleep behavior disorder (RBD) vs the RBD seen in multiple system atrophy (MSA) and Parkinson disease (PD). METHODS: Clinical features and VPSG measures were evaluated in 110 consecutive nondemented subjects (26 MSA, 45 PD, and 39 idiopathic RBD) free of psychoactive medications referred for suspected RBD to our sleep unit over a 5-year period, with extended follow-up (mean 26.9 +/- 21.3 months). RESULTS: Across the three groups studied, logistic regression analysis demonstrated that there were no differences in the quality of RBD symptoms (e.g., nature of unpleasant dream recall or behaviors witnessed by bed partners), most PSG variables, abnormal behaviors captured by VPSG, and clinical response to clonazepam. When compared to subjects with PD, however, patients with MSA had a significantly shorter duration of disease, a higher REM sleep without atonia percentage, a greater periodic leg movement index, and less total sleep time. Subjects with idiopathic RBD, as compared to those with either MSA or PD, were more often male, had greater self-reported clinical RBD severity, and were more often aware of their abnormal sleep behaviors. CONCLUSIONS: REM sleep behavior disorder (RBD)-related symptoms and neurophysiologic features are qualitatively similar in RBD subjects with the idiopathic form, multiple system atrophy (MSA), and Parkinson disease (PD). Polysomnographic abnormalities associated with RBD in the setting of MSA are greater than in PD, suggesting a more severe dysfunction in the structures that modulate REM sleep.

Age of Onset↗

Performance on the PD test battery by relatives of patients with progressive supranuclear palsy.

OBJECTIVE: To determine whether there is a greater prevalence of asymptomatic first-degree relatives (FDR) of patients with progressive supranuclear palsy (PSP) performing abnormally on the PD test battery (PD Battery) compared to sex- and age-matched normal control (NC) individuals. The PD Battery incorporates tests of motor function, olfaction, and mood. It has high specificity and sensitivity in distinguishing mildly affected PD patients from NC individuals in previous studies. METHODS: This test battery and regression analysis-derived scoring equations were applied to asymptomatic FDR. RESULTS: Twenty-three FDR and 23 NC individuals were tested. Of the FDR, 39% scored in the abnormal range, whereas none of the NC individuals achieved abnormal scores. This difference was significant. Further analysis demonstrated that the two groups differed significantly on a measure of simple reaction time. CONCLUSIONS: The proportion of FDR who demonstrated abnormal performance on the PD Battery was greater than NC individuals. Thus, the PD Battery may detect the asymptomatic carrier state or risk for PSP or a subclinical effect of a shared environmental exposure.

Adult↗

MAOB intron 13 and COMT codon 158 polymorphisms, cigarette smoking, and the risk of PD.

BACKGROUND: A polymorphism (G to A transition) in intron 13 of the mitochondrial enzyme monoamine oxidase B (MAOB) gene may modify, alone or by interacting with the catechol-O-methyltransferase (COMT(LL)) genotype (low enzymatic activity), the risk of idiopathic PD. Also, the association between never smoking and PD risk may be present only in people with the MAOB G allele. METHODS: The authors studied two ongoing prospective cohorts-the Nurses' Health Study (121,700 women aged 30 to 55 in 1976) and the Health Professionals' Follow-up Study (51,529 men aged 40 to 75 in 1986). They identified new PD cases through 1996, selected random control subjects matched on age and study cohort, and obtained DNA samples from blood or buccal smears from 85% of the eligible cases and 84% of the control subjects. They included genotypes from 214 cases and 449 control subjects, all Caucasian. RESULTS: The odds ratio of PD was 1.2 (95% CI 0.9, 1.7) for MAOB genotypes G/GG/GA compared with genotypes A/AA, and 1.1 (0.7, 1.8) for COMT genotypes LL compared with HH. The odds ratio (95% CI) was 1.7 (0.7, 3.9) for those with MAOB G/GG and COMT(LL) genotypes compared with those with MAOB A/AA and COMT(HH). There was a strong association between never smoking and PD risk in all groups defined by MAOB and COMT genotypes. CONCLUSION: The findings do not support a major role of the MAOB intron 13 polymorphism in the development of PD, either by itself or by interacting with smoking.

Adult↗

Negative regulation of T-cell function by PD-1.

PD-1 is a receptor inducibly expressed on CD4+ and CD8+ T cells following activation. PD-1-deficient mice develop signs of autoimmunity, suggesting a negative regulatory role for PD-1 in dampening lymphocyte responses. The expression of one ligand for PD-1, designated PD-L1 or B7-H1, on tumor cells of a variety of histologies has suggested a potential mechanism for tumor escape from immune destruction. This review summarizes data regarding PD-1 and related negative regulatory receptors, focusing on implications for potentiating antitumor immunity in vivo.

Animals↗

Sociodemography of borderline personality disorder (PD): a comparison with Axis II PDs and psychiatric symptom disorders convergent validation.

A theoretical objective of the present meta-analysis based upon data derived from a previously reported review (Taub, 1995), was to test two inductive hypotheses empirically regarding educational background and social class across different criteria for the DSM-III diagnosis of borderline personality disorder (PD). A secondary purpose was to determine whether comorbidity of borderline PD with other Axis II PDs would significantly delineate socioeducational variables. Across 7/8 pairwise contrasts which represented five studies, distribution of Hollingshead Redlich (H-R) social classes II-IV borderline PD (N = 326) significantly exceeded that in 457 diagnostic controls with Axis II PDs and psychiatric symptom disorders. Although average differences, as well as, interactions reflected by values of the H-R two-factor scale attained statistical significance these were were less consistent in magnitude and direction versus outcomes yielded by distribution of social classes. For the borderline PD diagnosis, the inductive hypotheses were substantiated by findings of significantly advanced scholastic achievement, as well as the younger age of most cohorts versus diagnostic controls with Axis II PDs and psychiatric symptom disorders; and in pairwise contrasts of outpatients with hospitalized cohorts. Comorbidity of the borderline PD diagnosis was associated with significantly lower social class, scholastic achievement and to a lesser extent, more severe psychopathology. Evidence for predominantly convergent validation relative to the socioeducational variables was substantiated by comparisons with (a) cohorts selected by criteria of the DSM-III-R, Gunderson's DIB and Borderline Personality Scale: (b) Norwegian females admitted to Gaustad Hospital and (c) patients with the DSM-III diagnosis of borderline PD attending an outpatient clinic in Norway.

Adult↗

Comparison of in vitro AGE formation between standard PD fluid and a novel bicarbonate/lactate formulation.

Peritoneal advanced glycation end-product (AGE) formation may be accelerated by glucose degradation products produced as a consequence of heat sterilization of peritoneal dialysis (PD) fluid. The formation of these degradation products is reduced if the glucose is separated from the buffers during heat sterilization. This pilot study compared in vitro AGE formation in PD fluid (1.36% and 3.86% glucose) heat sterilized in a two-compartment bag (bicarbonate/lactate buffer) with that in a standard, single-compartment bag (lactate buffer, Dianeal). Peritoneal dialysis fluids were incubated with human serum albumin (HSA, 1 g/L), as a model protein, at 37 degrees C for 0, 5, and 20 days. Formation of AGEs was assessed by measuring fluorescence at each time point. Advanced glycation end-product formation was greater in lactate PD fluid compared with bicarbonate/lactate PD fluid of equivalent glucose strength. Advanced glycation end-product formation in the lactate PD fluid containing 1.36% glucose was comparable to that in the bicarbonate/lactate PD fluid containing 3.86% glucose. The rate of increase in fluorescence per day was greater in the first 5 days of incubation than in the subsequent 15 days. These results are compatible with the presence of greater amounts of glucose-degradation products in the standard single-compartment bag resulting in enhanced AGE formation.

Bicarbonates↗

The role of vascular endothelial growth factor-A (VEGF-A) and platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) in Paget's disease of the vulva and breast.

BACKGROUND: Paget's disease of the vulva and the breast are uncommon conditions. The pathogenesis underlying these diseases is still unclear. Vascular endothelial growth factor-A (VEGF-A), a potent angiogenic factor, has been demonstrated in a variety of tumour cell types and is thought to be involved in tumour expansion. Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) has also been shown to stimulate angiogenesis. MATERIALS AND METHODS: Fifty-four cases of Paget's disease of the vulva, including 10 with an associated invasive adenocarcinoma, and 38 cases of Paget's disease of the breast, including 26 with available associated ductal carcinoma in situ (DCIS) and/or invasive carcinoma of the breast, were evaluated immunohistochemically for the expression of VEGF-A and PD-ECGF/TP. RESULTS: VEGF-A was not expressed in Paget's disease of the vulva or breast. PD-ECGF/TP was expressed in 22 out of 54 (41%) cases of Paget's disease of the vulva. Four of the cases associated with invasive disease (40%) expressed PD-ECGF/TP. Twenty-one out of 38 (55%) cases of Paget's disease of the breast were positive for PD-ECGF/TP. CONCLUSION: Our data suggest that PD-ECGF/TP may have a role to play in the pathogenesis of Paget's disease of the vulva and the breast. The role of VEGF-A in Paget's disease of the vulva and the breast remains to be fully elucidated.

Breast Neoplasms↗

Effects of G-6-PD deficiency, experimentally induced or genetically transmitted, on the sorbitol pathway activity. In vitro and in vivo studies.

Aldose reductase catalyzes the NADPH-linked reduction of hexoses to their respective sugar-alcohols, which are involved in the pathogenesis of "sugar-cataracts". In the lenses, the reaction catalyzed by G-6-PD is the source of NADPH supply blocking sugar-alcohol formation and consequently prevents or delays the onset of "sugar-cataracts". We have investigated the effect of G-6-PD deficiency, either experimentally induced or genetically transmitted, on the sorbitol accumulation in whole cells incubated in high glucose media and on the "sugar-cataracts" formation in a galactosemic rat model. We also screened 31 Negro male adults with diabetes mellitus for red cell G-6-PD deficiency. G-6-PD deficiency produced a significant inhibition on sorbitol accumulation in rat lenses and human red cells incubated in 50 mM glucose. In the galactosemic rat model G-6-PD deficiency experimentally induced with acetaminophen delayed the development of cataracts. Finally, two diabetic individuals were G-6-PD deficient and did not show cataracts whereas cataracts were identified in six other diabetic patients.

Acetaminophen↗

PD fluids contain high concentrations of cytotoxic GDPs directly after sterilization.

OBJECTIVE: Glucose degradation products (GDPs) in peritoneal dialysis (PD) fluids are cytotoxic and affect the survival of the peritoneal membrane. One of the most reactive GDPs in PD fluids is 3,4-dideoxyglucosone-3-ene (3,4-DGE). 3,4-DGE has been reported as an intermediate between 3-deoxyglucosone (3-DG) and 5-hydroxymethyl furaldehyde (5-HMF) during degradation of glucose. In PD fluids, 3,4-DGE exists in a temperature-dependent equilibrium with a pool of unidentified substances. The aim of this study was to explore this equilibrium and its temperature dependence during the first months of storage after the sterilization procedure. METHODS: GDPs and inhibition of cell growth (ICG) were measured directly after sterilization of the PD fluid and during storage at different temperatures for 60 days. The following GDPs were analyzed: 3-DG, 3,4-DGE, 5-HMF, formaldehyde, acetaldehyde, glyoxal, and methylglyoxal. RESULTS: Immediately after sterilization, the concentration of 3,4-DGE was 125 micromol/L. During the first weeks of storage, it decreased by about 80%. At the same time, the 3-DG concentration increased. None of the other GDPs were significantly affected. Cytotoxicity correlated well with the concentration of 3,4-DGE. When pure 3,4-DGE was substituted for the lost amount of 3,4-DGE after 30 days of storage, the initial ICG was almost completely regained. CONCLUSIONS: Heat sterilization of PD fluids promotes the formation of large quantities of 3,4-DGE, rendering the fluid highly cytotoxic. During storage, the main part of 3,4-DGE is reversibly converted in a temperature-dependent manner to a less cytotoxic pool, consisting mainly of 3-DG. Cytotoxicity seems to be dependent exclusively on 3,4-DGE. In order to avoid higher levels of 3,4-DGE concentrations, PD fluids should not be used too soon after sterilization and should not be stored at temperatures above room temperature.

Aldehydes↗

Long-term outcome in PD morbidity and mortality.

Two main dialysis modalities exist to treat chronic uremic patients: hemodialysis (HD) and peritoneal dialysis (PD); the latter is used less extensively than the former, but its penetration greatly differs among countries and among different regions of the same country. The comparison of the outcome in PD and HD is not easy, since many factors (mainly criteria for patient selection) oppose an adequate balance of the many factors influencing the patient's outcome. After the very different results in favor of HD in the early '80s, the difference in patient survival between PD and HD is progressively reduced and, in the '90s, many studies have shown comparable results. As far as the cardiovascular system is concerned, PD has some advantages versus HD due to stability in blood volume and electrolyte concentration, and lack of hyperkinetic circulation due to artero-venous fistula. However, this does not positively affect cardiovascular mortality whose prevalence is similar between the two modalities. Factors suggested to explain this unexpected result, namely: some degree of thrombophilia in PD, greater lipid metabolism derangement, and chronic fluid overload. Probably for these reasons, the de novo appearance of cardiovascular disease is similar in both modalities. Technique success is definitely worse in PD in nearly all the papers published. Many improvements in peritoneal solution biocompatibility have been made during the late '90s, but their effects on long-term outcome have to be defined.

Humans↗

[Research of the effect of ascorbic acid prereduced Pd in the determination of micro quantity of Mn with GFAAS].

In this article, method of determination of micro quantity of Mn with GFAAS and Pd have been researched, results of different additional methods of Pd were compared the combining energy of Pd in three heating steps were determined by X-ray Photoelectron Spectroscopy. The point was given that as a catalyst reduced Pd changed courses of Mn atomization, and when pre-reduced Pd was used because of its much larger surface area, method had much better RSD and had much stronger signal than other methods in those cases Pd was used too.

Ascorbic Acid↗

In vitro binding profile and in vivo pharmacological properties of the K-opioid compound PD 117302.

The in vitro binding profile and some in vivo pharmacological properties of (+/-)trans-N-Methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzo[b]-thiophene- 4-acetamide (PD 117302) were tested in rats. In rat brain membrane preparation, PD 117302 was selective for the k-binding sites, its KI (3.51 nM) being respectively about 200 and 1300 times lower at k- than at mu- and delta-sites. In vivo, PD 117302 injected intravenously (i.v.) showed dose-related analgesic effects in the 55 degrees C hot-plate test (peak-time 5 min) and in the paw pressure test. In both tests high doses of naloxone were required for full antagonism. PD 117302, injected i.v., produced dose-related diuresis in normally hydrated rats, which was prevented by 2 mg/kg of subcutaneous naloxone or diprenorphine. PD 117302 at doses between 0.125 and 2 mg/kg i.v. did not delay the gastrointestinal transit of a charcoal meal and did not antagonize morphine-induced constipation. Thus PD 117302 has good selectivity for k-binding sites in vitro and induces analgesia and diuresis, but does not slow gastrointestinal transit in vivo, supporting its k-agonist activity.

Analgesia↗

PD trivia: Making learning fun.

Nurses are educators. It is the aim of every educator that his or her teaching should translate into learning. Effective teaching is especially of importance in assuring that patients learn to perform their own peritoneal dialysis (PD). In facilitating an environment where learning can occur, making learning fun is the objective. It is with this mandate that PD Trivia was created. PD Trivia is an interactive game created to facilitate and reinforce learning. PD Trivia consists of 100 essential questions to making PD a success at home. Evaluations at the peritoneal dialysis clinic have revealed excellent quantitative and qualitative results of this simple but comprehensive teaching tool for effective learning of PD.

Adult↗

Male infertility in the hereditary polydactyly (PD) rat.

In the PD strain of rats, male pd homozygotes never sire, whereas male heterozygotes and female hetero- and homozygotes are fertile. In order to investigate the cause of infertility, pd/pd males were examined for their reproductive ability and gross and histological changes in the reproductive organs. Mating ability of pd/pd males was comparable to that of pd/+ males when a 2 week cohabitation procedure was employed. Cryptorchidism, which is considered to be a cause of infertility, was observed in 63% of the 12 week old pd/pd males. However, this abnormality frequently was observed unilaterally and the incidence of bilateral cryptorchidism was only 13%. Although the relative weights of descended testes and epididymides were comparable between the pd/pd and pd/+ males at 3 and 6 weeks of age, the values at 9 and 12 weeks of age were significantly lower in pd/pd males than in pd/+ males. A marked difference was not noted in relative weight changes of the seminal vesicles and prostate between the pd/pd and pd/+ males. Histological examination revealed defects in spermatogenesis in both descended and undescended testes in pd/pd males. The changes first appeared at 9 weeks of age and included vacuolation of nuclei of spermatocytes and spermatids, degeneration of spermatids, and occasionally multinucleated giant cells in the seminiferous tubules. In accessory sexual organs such as the epididymides, seminal vesicles, and prostate, no histological abnormalities were detected. These findings indicate that the substantial cause of infertility in pd/pd males is a disorder of spermatogenesis through which functionally normal spermatozoa are not produced.

Animals↗

Coordination of Gly-Tyr x Pd(II) complex to GMP nucleotide.

Coordination of the glycyl-L-tyrosinate x Pd(II) complex to guanosine-5'-monophosphate (GMP) has been studied using 1H, 13CV NMR and electron spectra methods. Two kinds of monomeric ternary complexes were found in aqueous solutions: Gly-Tyr x Pd(II)-N7(GMP) complex (Pd-N7) at pH range 3 - 9 and Gly-Tyr x Pd(II)--N1(GMP) complex (Pd-N1) at pH above 5.2. The influence of the aromatic ring of tyrosine upon the chemical shifts for the -N7 bonded nucleotide molecule suggest that the plane of the purine ring and that of the Gly-Tyr x Pd(II) complex are almost perpendicular to each other.

Chemical Phenomena↗

Heat sterilized PD-fluids impair growth and inflammatory responses of cultured cell lines and human leukocytes.

We have recently demonstrated that commercial PD-fluids inhibit the growth of a cultured mouse fibroblast cell line. Toxic substances produced during heat sterilization were believed to be the probable cause of the growth inhibition. The aim of the present study was to investigate if heat sterilized PD-fluids affect other cell types and other cellular functions than the growth of fibroblasts. The effect of three commercially and one laboratory made PD-fluid on cell growth of a mouse macrophage cell line (RAW) and a human neuroblastoma cell line (SH-SY5Y) was examined. The influence on stimulated release of tumour necrosis factor alpha (TNF alpha) from the macrophage cell line and stimulated superoxide generation from freshly prepared human leukocytes were also investigated. Compared to the filter sterilized PD-fluid, we found that heat treated PD-fluids significantly inhibited the growth of the two cell lines and impaired the stimulated release of TNF alpha and superoxide radicals. These results demonstrate that heat sterilization of PD-fluids produces substances that are cytotoxic regardless of the cell species, the cell type or the cell function tested.

Animals↗

PD treatment for severe congestive heart failure.

Our objective was to evaluate if peritoneal dialysis (PD) could improve survival of patients with progressive severe congestive heart failure resistant to drug therapy. The patients were selected by the cardiologist in cooperation with a nephrologist, including patients not responding to conventional medication with an expected fatal outcome within the next months. The study included 16 consecutive patients with a chronic progressive severe refractory heart failure (sHF) of NYHA class III (n = 6) or IV (n = 10) who did not respond to diuretics and angiotension converting enzyme (ACE) inhibitors. They had a mean age of 60 years (+/- 14, range 30-75, median 62 years). Nine of the patients had sHF as the only reason for initiating PD (all NYHA IV), while 7 also needed dialysis due to uremia. Five of 7 had been on hemodialysis but switched to PD due to a progressive congestive sHF. In 2 patients, PD was decided already at start of dialysis therapy due to the severity of their heart failure. The reason for sHF was: valvular dysfunction (n = 5) with defect prosthesis (n = 3); in the course of a myocardial infarction (n = 4); and cardiomyopathy (n = 4). Tenckhoff catheters were inserted under local anesthesia and ultrafiltration was started and maintained until discharge. The survival time and change in heart size by x-ray was used for analyses. All patients improved their stage of congestive heart failure by NYHA classification already during the first month. Six patients died during the follow-up period due to cardiac reasons (sudden death, relapse of sHF) after a mean of 10.7 months (+/- 3.7, range 1-24 months). Ten were alive after a median observation period of 10 months (+/- 12.5, range 1-36 months). Heart size was reduced in 15 of the patients. Three of the patients with sHF but without uremia could stop the PD. The results showed that ultrafiltration by PD was easy to perform despite low initial blood pressure. The sHF was reduced and life span was prolonged with improved quality of life.

Adult↗

Endothelin A receptor antagonism by PD 156707 does not reduce infarct size after coronary artery occlusion/reperfusion in pigs.

Episodes of myocardial ischemia are associated with increases in cardiac venous plasma endothelin (ET) concentrations, suggesting that ET may play a role in the development of myocardial infarction. The purpose of this study was to determine if selective blockade of ET(A) receptors by PD 156707 reduces infarct size caused by coronary artery occlusion and reperfusion in pentobarbital-anesthetized micropigs. A PD 156707 dose which selectively blocks the ET(A)-mediated vasopressor response, but not the ET(B)-mediated vasodepressor response to i.v. ET-1 challenges (0.3 nmol/kg), was established in dose ranging studies in anesthetized micropigs. In myocardial infarction studies, micropigs received either saline vehicle (n = 7) or PD 156707 (n = 8) at a loading dose of 10 mg/kg/1 hr, followed by a maintenance dose of 7 mg/kg/hr. Coinciding with the start of the maintenance dose, the left anterior descending coronary artery was occluded for 1 hr followed by 3 hr of reperfusion. PD 156707 caused a significant (29 mm Hg) decrease in arterial blood pressure before occlusion. PD 156707 had no effect on infarct size (61.1 +/- 5.6% of the region at risk in the PD 156707 treatment group vs. 70.1 +/- 3.9% in the control group). These results suggest that ET(A) receptor activation does not substantially contribute to coronary artery occlusion/reperfusion-induced myocardial infarction.

Animals↗