The Parkinson''s Disease Questionnaire (PDQ-39): development and validation of a Parkinson''s disease summary index score

We present a series of 38 cases of longitudinal splitting of the peroneus brevis tendon revealed by MR imaging (12 lesions were confirmed at surgery). MRI enabled classification in four surgical grades. The frequency of such lesions in chronic ankle instability as observed in our series is often reported in the literature. Bilateral cases are common. Asymptomatic cases do occur, especially in grades I and II. MRI has been shown to be a very effective investigation for demonstrating this tendinous lesion; the proton density weighted sequence in the axial plane is the most adequate sequence.     

Parkinson''s disease: diagnosis, pathology, and treatment

Limiting dilution analysis technique was used to enumerate the circulating precursor frequency of donor and third-party-reactive helper T lymphocytes (HTLpf) in 28 renal allograft recipients before (pre-tx) and at three intervals (T1: 60-90 days, T2: 120-180 days, T3: 360-1620 days) after transplantation (post-tx). Two patterns of responses were identified, in group 1 (n = 12), a five to 31-fold reduction of donor-reactive HTLpf (ranging from 1/19231-1/62500) occurred within 90-1620 days post-tx, while in group 2(n = 16), no significant changes of donor-reactive HTLpf were seen. In both groups, the third-party-reactive HTLpf in most of these patients remained largely unchanged throughout the study period. The number of HLA-DR mismatches, total number of rejection episodes, serum creatinine levels, and biopsy findings at T3 were compared in both groups using Fisher's exact probability, and the Mann-Whitney test. We found that 11 patients (92%) in group 1 were HLA-DR compatible with donors, while nine (56%) patients in group 2 were HLA-DR compatible with donors, p = 0.04. In group 1 eight rejection episodes occurred in five (41.6%) patients during the study period, compared to 33 in 13 (81%) patients in group 2, p = 0.03. Group 1 had a significantly lower serum creatinine level (at T3); median: 136 vs 165 mumol/l for group 2, p = 0.03. Biopsy indicated no rejection (at T3) in eight (66%) patients in group 1 as compared to three (18%) patients in group 2, p = 0.03. Taken together, these results indicate that the frequency of circulating HTLpf correlate with the clinical status of the graft. Therefore monitoring of HTLpf in the peripheral blood could be useful in predicting graft outcome and selecting patients for reducing immunosuppression.     

Ribosomal protein insufficiency and the minute syndrome in Drosophila: a dose-response relationship

Minutes comprise > 50 phenotypically similar mutations scattered throughout the genome of Drosophila, many of which are identified as mutations in ribosomal protein (rp) genes. Common traits of the Minute phenotype are short and thin bristles, slow development, and recessive lethality. By mobilizing a P element inserted in the 5' UTR of M(3)95A, the gene encoding ribosomal protein S3 (RPS3), we have generated two homozygous viable heteroalleles that are partial revertants with respect to the Minute phenotype. Molecular characterization revealed both alleles to be imprecise excisions, leaving 40 and 110 bp, respectively, at the P-element insertion site. The weaker allele (40 bp insert) is associated with a approximately 15% decrease in RPS3 mRNA abundance and displays a moderate Minute phenotype. In the stronger allele (110 bp insert) RPS3 mRNA levels are reduced by approximately 60%, resulting in an extreme Minute phenotype that includes many morphological abnormalities as well as sterility in both males and females due to disruption of early gametogenesis. The results show that there is a correlation between reduced RPS3 mRNA levels and the severity of the Minute phenotype, in which faulty differentiation of somatic tissues and arrest of gametogenesis represent the extreme case. That heteroalleles in M(3)95A can mimic the phenotypic variations that exist between different Minute/rp-gene mutations strongly suggests that all phenotypes primarily are caused by reductions in maximum protein synthesis rates, but that the sensitivity for reduced levels of the individual rp-gene products is different.     

Validation of a telephone questionnaire for Parkinson''s disease

Unfractionated as well as low-molecular-weight heparins (LMWH) are known to cause an increase in blood levels of tissue factor pathway inhibitor (TFPI). To study the effect of a newly developed supersulfated LMWH (IK-SSH, Iketon Farmaceutici) on TFPI concentrations in human plasma, the compound was injected into volunteers at doses of 0.14, 0.33 and 0.66 mg/kg intravenously or 0.33, 0.66 and 1.0 mg/kg subcutaneously. At certain known times blood was drawn and plasma levels of both total and free TFPI were measured using enzyme-linked immunosorbent assay methodology. Baseline plasma concentrations of TFPI were 72.2+/-3.1 ng/ml for total and 10.8+/-0.8 ng/ml for free TFPI. Intravenous or subcutaneous injection of IK-SSH led to a strong and long-lasting rise in TFPI levels which were increased more than 5-fold for total TFPI and more than 30-fold for free TFPI. Maximum TFPI levels were reached 5-10 min after intravenous and 60 min after subcutaneous administration. IK-SSH caused prolongation of ex-vivo clotting times in the APTT and Heptest assay, whereas thrombin time was not affected. Anticoagulant actions of IK-SSH showed a significant correlation to plasma concentrations of TFPI and they are thought to be based at least partially on the release of TFPI from vascular sites.     

Protein nitration in Parkinson''s disease

The development of five schistosome species was compared in mice by the recovery of schistosomula from chopped lung tissue and of adult worms by portal perfusion. Three developmental patterns appeared. (1) Schistosoma japonicum was unique in showing an early establishment of schistosomula in and a rapid departure from the lungs together with the highest worm recovery; (2) S. haematobium contrasted by establishing later and persisting in the lungs for at least 2 weeks while yielding the lowest adult worm recovery; and (3) S. intercalatum, S. mansoni, and S. rodhaini had an intermediate pattern--they resided in the lungs for several days, then disappeared and produced intermediate numbers of adults. Lung petechiae, known to accompany the migration of S. japonicum, were never detected after infection with the other species. We speculate that the three migration patterns of schistosomes are related to the size of the relative spectra of naturally infected definitive hosts.     

Current therapy of Parkinson''s disease

OBJECTIVE: To study the outcome of pregnancy in overt diabetes with retinopathy and the changes of retinopathy during pregnancy. METHOD: Retrospective study was made on 49 pregnancies with overt diabetes from 1981 to 1995. RESULTS: Maternal complications and perinatal morbidity were higher in pregnancies with retinopathy but there were no significant differences between those with and without retinopathy. Retinopathy progressed during pregnancy i 31.1% of the parturients. CONCLUSION: Pregnancies with overt diabetes complicated with retinopathy are not the indications for terminating pregnancy, but the changes of retinopathy should be carefully monitored during pregnancy.     

Early morning dystonia in Parkinson''s disease

Proliferation of arterial smooth muscle cells has held center stage as the culprit in restenosis for almost two decades. Many strategies for combating restenosis target smooth muscle replication. However, none have proven beneficial in clinical trials. Indeed, inhibition of smooth muscle proliferation in human patients might produce the undesired effect of destabilizing vulnerable atherosclerotic plaques because these cells furnish the collagen responsible for the biomechanical strength of the plaque. Actually, in some cases the benefit of angioplasty may depend on stimulating smooth muscle replication and collagen elaboration, converting an "unstable" to a more stable plaque. Moreover, recent clinical and experimental evidence suggests that restenosis depends less on neointimal hyperplasia than on constrictive remodeling (i.e., advential scarring, producing a smaller lumen), a process independent of smooth muscle replication. The recognition that plaques vulnerable to disruption often do not produce flow-limiting stenoses highlights a need for reassessment of the strategies to treat or prevent the acute coronary syndromes. We should strive to treat aggressively risk factors such as hyperlipidemia whose control appears to stabilize plaques. Trials are even underway comparing such risk factor management with coronary artery intervention. If we could identify potentially unstable atheroma before they are evident, clinically, we might even contemplate angioplasty of nonsignificant stenoses to induce smooth muscle cell proliferation and reinforce the plaque's fibrous cap. This proposal may seem preposterous, yet we perform "primary" angioplasty every day in patients with an acute myocardial infarction whose "culprit" lesions underlying the thrombus are often not critical. Our knowledge of the biology of restenosis has lagged behind our practice of coronary intervention. Advances in understanding the biology of the complications of interventional therapy, hand in hand with technical advances, should help us to devise more rational and enduring approaches to benefiting our patients.     

The subthalamic nucleus: a possible target for stereotaxic surgery in Parkinson''s disease

Agenesis of the sacrum is a rare anomaly that is associated with numerous visceral abnormalities, spinal cord malformation, and lower limb defects. A fatal case of sacral and lower lumbar agenesis in a 3-day-old female infant born at 38 weeks of gestation is reported. The extraneural malformations comprised an imperforate anus, a rectovaginal fistula, and musculoskeletal abnormalities, including several thoracocervical hemivertebrae and aplasia of the sacrum and the fourth and fifth lumbar vertebrae. The cervical and high thoracic spinal cord segments were normal. Disruption of secondary neurulation, possibly due to notochord dysfunction, was suggested by malformation of the ventral half of the lower thoracic spinal cord with relative preservation of the dorsal horns and, more caudally, by loss of all normal histological landmarks, including the central canal. Neither skeletal muscle nor myoblasts were found in muscle compartments that would normally have received motor innervation from the levels of the spinal cord from which anterior horn cells were absent, indicating parallel, segmental failure of myotomal differentiation in the caudal eminence.     

The health burdens of Parkinson''s disease

Glucocorticoid (GC) hormones induce apoptosis in lymphoid and leukemic cells by binding and activating cytosolic GC receptors. Because physiological stress often causes hormone-free GC receptor activation, we have investigated if stress-induced apoptosis of lymphoid cells is also mediated by the activation of the GC receptor pathway. In S49 T lymphoma cells, heat shock and deprivation of growth factors or nutrients caused nuclear translocation and loss of agonist binding capacity of GC receptors, similar to that in cells incubated with the glucocorticoid dexamethasone (DEX). In variant S49 H.2 cells, cross-resistance to DEX, temperature shocks and growth factor deprivation were associated with a higher threshold for hormone-dependent and -independent receptor activation in situ and with impaired in vitro activation of cytosolic receptors. Cross-resistance to DEX, low serum and heat shock was abrogated, however, by pharmacological sensitization of GC receptor activation with the drug meta-iodobenzylguanidine (MIBG). Sensitive S49 cells and resistant variants did not differ in the expression levels of the apoptosis-regulating genes bax, bad, bcl-X and bcl-2, the status of the p53 gene nor in a different requirement for the growth factors II-2, IL-4 or IL-9. The results suggest that ligand-independent activation of the GC receptor is a central signalling and controlling event in some forms of stress-induced apoptosis, assigning a novel function to the GC receptor in the regulation of lymphoid and leukemic cell numbers.     

Effect of selegiline on mortality in patients with Parkinson''s disease: a meta-analysis

What is the role of selective attention in visual perception? Before answering this question, it is necessary to differentiate between attentional mechanisms that influence the identification of a stimulus from those that operate after perception is complete. Cognitive neuroscience techniques are particularly well suited to making this distinction because they allow different attentional mechanisms to be isolated in terms of timing and/or neuroanatomy. The present article describes the use of these techniques in differentiating between perceptual and postperceptual attentional mechanisms and then proposes a specific role of attention in visual perception. Specifically, attention is proposed to resolve ambiguities in neural coding that arise when multiple objects are processed simultaneously. Evidence for this hypothesis is provided by two experiments showing that attention-as measured electrophysiologically-is allocated to visual search targets only under conditions that would be expected to lead to ambiguous neural coding.     

Medical treatment of essential tremor and Parkinson''s disease

Tremor is commonly the first neurologic sign of Parkinson's disease (PD) that leads patients to see a physician. Knowing how to differentiate the resting tremor of PD from essential tremor is an important diagnostic skill. Unlike patients with essential tremor, those with PD have other neurologic findings. A diagnosis of PD is likely if the patient has two of three major clinical features: resting tremor, bradykinesia, and rigidity. Minor signs may also be seen, including cognitive slowing, speech abnormalities, depression, dysautonomia, and sleep disturbances. The history and physical exam can determine if the patient has parkinsonism and whether the cause is Parkinson's disease.     

The genetics of Parkinson''s disease and parkinsonian syndromes

General anaesthesia with 80% CO2/20% O2 and 5% halothane in O2 (mask induction) was compared for castration of 3-4 week-old piglets. One group was castrated without anaesthesia. Of the noncastrated control groups one had CO2- and one halothane anaesthesia, one breathed room air through the induction system, and one was held in castration position. The behaviour to induction and castration was assessed, and the cortisol-, ACTH- and beta-endorphin plasma concentrations were determined to quantify the stress elicited by anaesthesia, castration and handling. Violent struggling and vocalization were elicited by CO2 and positioning into the mask induction system while breathing room air; halothane induction was quiet. CO2 induced profound surgical anaesthesia; whereas under halothane anaesthesia some animals exhibited still a slight reaction to castration. Recovery was fast, smooth and quite. Permanent violent struggling and vocalization were elicited by castration without anaesthesia. Plasma cortisol was not a sensitive tool to judge castration stress. The high ACTH and beta-endorphin plasma concentrations elicited by CO2 anaesthesia confirm our clinical experience. General anaesthesia is fast and safely induced with CO2 in piglets and castration can be performed without any reaction, but with CO2 anaesthesia the stress is not reduced.     

Gene therapeutic strategies for neuroprotection: implications for Parkinson''s disease

The model used for calculating perfusion by MRI techniques that use endogenous water as a tracer assumes that arterial water is a freely diffusible tracer. Evidence shows that this assumption is not valid in the brain at high blood flow rates, at which movement of water into and out of the microvasculature becomes limited by diffusion across the blood-brain barrier. In this work, the arterial spin-labeling technique is used to show that fraction of arterial water that is dependent on blood flow rate remains in the vasculature and does not exchange with brain tissue water. By using perfusion measurements without and with magnetization transfer (MT) effects, one can distinguish arterial label that exchanges into tissue because blood has much smaller MT than brain tissue. Using this technique, the extraction fraction for water is measured in the rat brain at various cerebral blood flow rates. At high flow rates (approximately 5 ml/g/min), the extraction fraction for water is found to be about 45% in rat brain. Disruption of the blood-brain barrier with D-mannitol caused an increase in the extraction fraction for water. It was possible to form an image related to the extraction fraction for water. The ability to estimate the amount of vascular water exchanging with tissue water by MRI may represent a noninvasive approach to detect the integrity of the blood-brain barrier.     

Parkinson Psychosis Rating Scale: a practical instrument for grading psychosis in Parkinson''s disease

Three hospital sites evaluated the Bayer two-pad urine dipstick as a screening test for microalbuminuria. One pad estimates albumin concentrations between 10 and 150 mg/L, and the second estimates creatinine values between 300 and 3,000 mg/L. The Boehringer Mannheim (BMD) Micral dipstick was also compared and evaluated. The accuracy of the dipsticks was judged by comparison with cuvet-based immunonephelometry for albumin and to standard rate-Jaffe methods for creatinine; these assays were well standardized and controlled and were assumed to give accurate values. Precision of these methods and that of the dipsticks was determined by multiple assays of control materials. Visual or instrument (Clinitek 50 or 100) evaluation of the Bayer or visual checks of the BMD albumin dipstick pad with patients' urines gave clinically acceptable accuracy. The albumin/creatinine ratio from the Bayer dipsticks gave better accuracy for albumin excretion than the albumin pads alone from either manufacturer. This ratio should permit making a good estimate of the 24-hr albumin excretion in a randomly collected urine.     

Short-term beneficial effect of deprenyl monotherapy in early Parkinson''s disease: a quantitative assessment

We report a case of giant ectopic pelvic spleen combined with an accessory spleen and confirmed by liver-spleen scan, angiography, magnetic resonance imaging, and surgical findings. In various reviews of the literature, no ectopic pelvic spleen larger than this one has been reported.     

Severity of perinatal cerebral injury and developmental outcome: A dose-response relationship.

The purpose of this study was to establish a dose–response relationship between extent of perinatal cerebral injury and quality of developmental outcome in childhood. To attain this goal, 54 school and preschool-age children who had incurred perinatal intracranial hemorrhage were recruited. The main index of hemorrhage severity—the degree of acute ventriculomegaly observed on the cranial ultrasonogram during the neonatal period—was significantly associated with outcome in all measured domains. These included verbal and nonverbal intelligence, motor skills, and behavioral problems associated with the externalizing and internalizing syndromal groupings. The putative neurobiological mechanisms underlying the observed dose–response relationship between perinatal lesion severity and developmental outcome are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)