Re: clinical feature profile of spinocerebellar ataxia type 1-8 predicts genetically defined subtypes.
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Autonomic Nervous System Diseases↗
Biomedical subjects
Joseph Friedman
Publications and source records attributed to Joseph Friedman.
REM sleep behavior disorder: a possible early marker for synucleinopathies.
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Biomarkers↗
Diffusion tensor imaging in schizophrenia.
BACKGROUND: Alignment of white matter axons as inferred from diffusion tensor imaging has indicated changes in schizophrenia in frontal and frontotemporal white matter. METHODS: Diffusion tensor anisotropy and anatomical magnetic resonance images were acquired in 64 patients with schizophrenia and 55 normal volunteers. Anatomical images were acquired with a magnetization prepared rapid gradient echo sequence, and diffusion tensor images used a pulsed gradient spin-echo acquisition. Images were aligned and warped to a standard brain, and anisotropy in normal volunteers and patients was compared using significance probability mapping. RESULTS: Patients showed widespread areas of reduced anisotropy, including the frontal white matter, the corpus callosum, and the frontal longitudinal fasciculus. CONCLUSIONS: These findings, which are consistent with earlier reports of frontal decreases in anisotropy, demonstrate that the effects are most prominent in frontal and callosal areas and are particularly widespread in frontal white matter regions.
Adolescent↗
The roles of sequencing and verbal working memory in sentence comprehension deficits in Parkinson's disease.
Studies of sentence comprehension deficits in Parkinson's disease (PD) patients suggest that language processing involves circuits connecting subcortical and cortical regions. Anatomically segregated neural circuits appear to support different cognitive and motor functions. To investigate which functions are implicated in PD comprehension deficits, we tested comprehension, verbal working memory span, and cognitive set-switching in a non-linguistic task in 41 PD patients; we also obtained speech measurements reflecting motor sequencing processes that may be involved in articulatory rehearsal within working memory. Comprehension of sentences with center-embedded or final relative clauses was impaired when they could not be understood from lexical semantic content alone. Overall comprehension error rates correlated strongly with impaired set-switching and significantly with reduced working memory span and speech motor sequencing deficits. Correlations with comprehension of different sentence structures indicate that these impairments do not represent a single deficit; rather, PD comprehension deficits appear to arise from several independent mechanisms. Deficits in cognitive set-switching or underlying inhibitory processes may compromise the ability to process relative clauses. Deficits in verbal working memory appear to impair comprehension of long-distance dependencies. Speech sequencing correlated with neither set-switching nor verbal working memory span, consistent with their being supported by independent, segregated cortico-subcortical circuits.
Aged↗
Non-movement disorder heralds symptoms of Machado-Joseph disease years before ataxia.
We describe three patients with the Machado-Joseph disease (MJD) genetic abnormality who had non-movement disorder neurological symptoms or signs that preceded the gait ataxia by several years. This implies that some clinical manifestations other than ataxia may be considered part of the herald symptoms of MJD, especially in the setting of a positive family history.
Adult↗
The longitudinal course of thought disorder in geriatric patients with chronic schizophrenia.
OBJECTIVE: This study longitudinally assessed previously validated dimensions of thought disorder--verbal underproductivity and disconnection--in geriatric schizophrenia and replicated previous cross-sectional differences in communication disorders. METHOD: Two hundred twenty patients with chronic schizophrenia were assessed with the Thought, Language, and Communication Scale over a mean follow-up period of 2.3 years. RESULTS: Patients had increases in verbal underproductivity but stable scores on disconnection over the follow-up period. Worsening in verbal underproductivity was associated with concurrent worsening in Mini-Mental State Examination scores and older age at baseline. CONCLUSIONS: Verbal underproductivity worsens with aging and is associated with cognitive worsening, although disconnected speech is relatively stable. Some geriatric patients with schizophrenia may lose the skills necessary to report symptoms, leading to the impression that their clinical status is improving.
Aged↗
Intrathoracic lymphadenopathy in hospitalized patients with pneumococcal pneumonia.
PURPOSES: Pneumococcal pneumonia is the most common etiology for community-acquired pneumonia. The prevalence of lymphadenopathy seen on CT scans in these patients is uncertain. The purpose of this series was to assess the prevalence of intrathoracic lymphadenopathy in hospitalized patients with pneumococcal pneumonia. MATERIALS AND METHODS: We retrospectively identified 35 hospitalized patients with pneumococcal pneumonia who had been evaluated with CT scanning between January 1998 and April 2002. There were 18 men and 17 women with a mean age of 56 years. The study inclusion criteria were as follows: blood culture positive for Streptococcus pneumoniae, clinical diagnosis of pneumonia, and chest CT scan. The study exclusion criteria were known causes of lymphadenopathy. Charts were reviewed for HIV status, smoking history, and comorbidities. CT scans were reviewed for the presence and degree of lymphadenopathy, and the characteristics of pneumonia. The number of enlarged lymph nodes was graded as few (one to two), moderate (three to five), or many (six or more). Pneumonias were described by location, the number of involved lobes, the presence of cavitation, and the presence of pleural effusion. Patients with different comorbidities and different imaging characteristics of pneumonia were compared. RESULTS: Among the 35 patients with pneumococcal pneumonia, intrathoracic lymphadenopathy was present on CT scans in 54% of patients (19 of 35 patients). The lymphadenopathy was ipsilateral to the pneumonia in 100% of patients (19 of 19 patients). One patient also had contralateral lymphadenopathy. The lymphadenopathy was graded as few in 37% of patients (7 of 19 patients), moderate in 37% of patients (7 of 19 patients), and many in 26% of patients (5 of 19 patients). The pneumonia was right-sided in 26% of patients (9 of 35 patients), left-sided in 17% of patients (6 of 35 patients), and bilateral in 57% of patients (20 of 35 patients). Comorbidities included the following: HIV infection (n = 15); smoking (n = 21); emphysema (n = 5); hepatitis C (n = 5); and diabetes (n = 3). The characteristics of pneumonia included the following: multilobar (n = 25); pleural effusion (n = 25); and cavitation (n = 5). The prevalence of lymphadenopathy according to comorbidities and characteristics of pneumonia ranged from 40 to 100%. None of the differences in prevalence of lymphadenopathy among the subgroups was statistically significant. CONCLUSION: Lymphadenopathy is a common CT scan feature of pneumococcal pneumonia in hospitalized patients, in a variety of settings. Therefore, when a patient with pneumococcal pneumonia has lymphadenopathy seen on a CT scan, other etiologies for the lymphadenopathy need not be suspected.
Adult↗
Double-blind, randomized, controlled trial of rasagiline as monotherapy in early Parkinson's disease patients.
Rasagiline (N-propargyl-1(R)-aminoindan) mesylate is a potent, selective, and irreversible monoamine oxidase-B inhibitor. This study was designed to evaluate the safety, tolerability, and preliminary efficacy of rasagiline monotherapy in early Parkinson's disease (PD) patients not receiving levodopa. The study was performed as a multicenter, parallel-group, double-blind, randomized, placebo-controlled, 10-week study. Fifty-six PD patients were randomly assigned to rasagiline mesylate 1, 2, or 4 mg once daily, or placebo. A 3-week dose-escalation period was followed by a 7-week maintenance phase. At week 10, the mean (+/-SE) changes from baseline in total Unified Parkinson's Disease Rating Scale (UPDRS) score were -1.8 (+/-1.3), -3.6 (+/-1.7), -3.6 (+/-1.2), and -0.5 (+/-0.8) in the rasagiline 1, 2, and 4 mg/day and placebo groups, respectively. Analysis of responders showed that 28% of patients (12 of 43) receiving rasagiline had an improvement in total UPDRS score of greater than 30%, compared with none of the patients receiving placebo (P < 0.05, Fisher's exact test). The frequency and types of adverse events reported by rasagiline-treated and placebo-treated patients were similar. These results suggest that rasagiline monotherapy is well tolerated and efficacious in early PD.
Adult↗
Working memory performance in poor outcome schizophrenia: relationship to age and executive functioning.
Performance on the Letter-Number Sequencing (LNS) and Wisconsin Card Sorting Tests (WCST) have been shown to be significantly correlated in patients with schizophrenia, a relationship postulated to be due to working memory demands of the two tests (Gold, Carpenter, Randolph, Goldberg, & Weinberger, 1997). An alternative explanation for the association between these two tests is their sorting demands, in that both require sorting of information albeit in slightly different ways. If the latter explanation is valid, then working memory tasks that do not require sorting or other conceptualization demands should be less predictive of WCST performance than LNS. These hypotheses were examined in 34 poor outcome patients with schizophrenia, one-half of whom were over the age of 65. Patients were evaluated on Digit Span Forward, spatial working memory, LNS, and the WCST. It was found that WCST performance was significantly associated with performance on the LNS but no other working memory task. Age related performance differences were greatest on the WCST Categories and floor effects were noted on this test in one-half of the subjects. Analyses predicting WCST Categories in subjects whose scores were greater than zero (n = 16) also demonstrated that LNS, but not Digit Span or spatial working memory (any delay) predicted WCST performance. These findings indicate that LNS may be an index of executive functioning, particularly in patients who cannot perform the WCST.
Adult↗
Oxidative stress in hypertensive,diabetic, and diabetic hypertensive rats.
BACKGROUND: Reactive oxygen species play a key role in the formation of endothelial dysfunction accompanying diabetes mellitus, hypertension, and other cardiovascular diseases. METHOD: This study compares oxidative stress (OS) in Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), non-insulin-dependent Cohen Diabetic rats (CDR), and Cohen Rosenthal diabetic hypertensive rats (CRDH), a unique animal model of both diabetes and hypertension. The OS was evaluated with a newly developed thermochemiluminiscence (TCL) analyzer (Lumitest Ltd., Nesher, Israel) that measures the oxidizability (ie, susceptibility to oxidation) of a test sample. RESULTS: The TCL oxidizability test results of sera from the different rats groups showed a time-dependent increase in TCL of up to 145% +/- 7% for WKY, 160% +/- 8% for SHR, 179% +/- 12% for CDR, and 226% +/- 15% for CRDH. These results were significant: P <.001 for SHR and CDR and P <.0001 for CRDH in comparison to WKY. Lipid peroxide levels also increased in each strain of rats: to 80 +/- 7.8 nmol/mL in WKY, 104 +/- 10.1 nmol/mL in SHR, 110 +/- 9.4 nmol/mL in CDR, and 167 +/- 11.7 nmol/mL in CRDH. These results were also significant: P <.001 for SHR, CDR and CRDH in comparison to WKY. CONCLUSION: The combination of hypertension and diabetes is accompanied by higher oxidative stress than that seen with either disorder alone.
Animals↗
Putrescine activates oxidative stress dependent apoptotic death in ornithine decarboxylase overproducing mouse myeloma cells.
Accumulation of putrescine in ornithine decarboxylase overproducing cells provokes apoptotic death that is inhibited by 2-difluoromethylornithine, a specific inhibitor of ODC. The apoptotic process provoked by putrescine involves the release of cytochrome c from the mitochondria and activation of caspases cascades demonstrated by the cleavage of caspase-2, polyA-ribose polymerase (PARP), and proteolytic cleavage of the translation initiation factor 4G (eIF4G). The general caspases inhibitor BD-fmk inhibits PARP cleavage but not cell death. Aminoguanidine, an inhibitor of amine oxidases, inhibits the cleavage of PARP and cell death, whereas the antioxidant BHA inhibits PARP cleavage but not cell death. The intracellular Ca2+ chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester (BAPTA/AM) inhibits both PARP cleavage and cell death. Although the ability of BAPTA/AM to inhibit the induction of apoptosis may suggest that the accumulating putrescine stimulates the release of Ca2+, such a Ca2+ elevation was not observed. We suggest that the accumulation of putrescine leads to oxidative stress that causes cell death.
Animals↗
A family with a tau P301L mutation presenting with parkinsonism.
We report a sib-pair with a tau P301L mutation. Unlike most previous cases with this mutation, parkinsonism, rather than dementing features were the predominant and presenting feature. We have also observed that the P301L mutation has occurred on the H1 tau haplotype background. The haplotype background may influence the disease phenotype since in many previous Caucasian families with the P301L mutation, the haplotype background has been H2.
Diagnosis, Differential↗
Electroconvulsive Therapy in Parkinson's Disease: A Report on Five Cases.
Five patients with Parkinson's disease (PD) and depression underwent electroconvulsive therapy (ECT). One patient had a myocardial infarction several hours after the last planned session and died. Of the remaining four patients, all achieved marked improvement in mood and three had markedly improved motor function as well. Improvement in motor function lasted as long as 8 weeks. ECT is helpful in treating both depression and parkinsonism but maintenance ECT is required for continued motor improvement.
Journal Article↗