Tau uptake in agrammatic primary progressive aphasia with and without apraxia of speech.

BACKGROUND AND PURPOSE: The non-fluent/agrammatic variant of primary progressive aphasia (agPPA) is a heterogeneous diagnosis wherein some individuals have apraxia of speech (AOS). When agPPA includes AOS, a tauopathy is the likely underlying pathology. Recently, [18F]AV-1451 was developed for the in-vivo assessment of tau. In this study, we compared patterns of tau tracer uptake in patients with agPPA with and without AOS. METHODS: Nine patients with agPPA (four without AOS) underwent tau positron emission tomography imaging with [18F]AV-1451. Uptake of [18F]AV-1451 was assessed as cortical to cerebellar crus ratio (standard uptake value ratio) in cortical regions of interest measured using the MCALT atlas and compared voxel-wise in SPM12. Each patient was age- and sex-matched to three controls. RESULTS: The agPPA without AOS showed uptake in the left frontal and temporal lobes, whereas agPPA with AOS showed uptake in the bilateral supplementary motor areas, frontal lobes, precuneus and precentral gyrus relative to controls. The left precentral gyrus had uptake in agPPA with AOS relative to those without AOS. CONCLUSIONS: This cross-sectional study suggests that [18F]AV-1451 uptake in the precentral gyrus is implicated in AOS in agPPA.

Clinical and imaging characterization of progressive spastic dysarthria.

BACKGROUND AND PURPOSE: To describe speech, neurological and imaging characteristics of a series of patients presenting with progressive spastic dysarthria as the first and predominant sign of a presumed neurodegenerative disease. METHODS: Participants were 25 patients with spastic dysarthria as the only or predominant speech disorder. Clinical features, pattern of MRI volume loss on voxel-based morphometry and pattern of hypometabolism on F18-fluorodeoxyglucose positron emission tomography (FDG-PET) scan are described. RESULTS: All patients demonstrated speech characteristics consistent with spastic dysarthria, including strained voice quality, slow speaking rate, monopitch and monoloudness, and slow and regular speech alternating motion rates. Eight patients did not have additional neurological findings on examination. Pseudobulbar affect, upper motor neuron pattern limb weakness, spasticity, Hoffman sign and positive Babinski reflexes were noted in some of the remaining patients. Twenty-three patients had electromyographic assessment and none had diffuse motor neuron disease or met El Escorial criteria for amyotrophic lateral sclerosis. Voxel-based morphometry revealed striking bilateral white matter volume loss affecting the motor cortex (BA 4), including the frontoparietal operculum (BA 43) with extension into the middle cerebral peduncle. FDG-PET showed subtle hypometabolism affecting the premotor and motor cortices in some patients, particularly in those who had a disease duration longer than 2 years. CONCLUSIONS: A neurodegenerative disorder that begins focally with spastic dysarthria due to involvement of the motor and premotor cortex and descending corticospinal and corticobulbar pathways is characterized. The descriptive label 'progressive spastic dysarthria' to best capture the dominant presenting feature of the syndrome is proposed.

Involvement of CDKN2 (p16INK4A/MTS1) and p15INK4B/MTS2 in human leukemias and lymphomas.

CDKN2 (p16INK4A/MTS1) and p15INK4B/MTS2 have been shown recently to be potent inhibitors of the cyclin D/cyclin-dependent kinase 4 complex. Both genes are candidates for the putative tumor suppressor gene located at chromosome 9p21. We examined a series of 14 hematopoietic cell lines and 117 primary lymphoid tumors for deletion and mutation of these genes. The primary tumors included 65 T-cell malignancies and 52 B-cell malignancies. The cell line study revealed 4 of 4 T-ALL lines to have homozygous deletions of CDKN2. Two of the 4 lines also showed homozygous deletions of MTS2, while the remaining 2 lines retained both MTS2 alleles. In the primary tumors, homozygous deletions of both CDKN2 and MTS2 were found in 35% of the T-ALL/lymphoblastic lymphoma (8 of 23). Homozygous deletions of both genes also occurred in 1 of 3 precursor B-ALLs. PCR-single strand conformational polymorphism analysis of CDKN2 exons 2 and 3 and MTS2 exon 2 failed to demonstrate mutations in either CDKN2 or MTS2 in any of the T- or B-cell malignancies, with two possible exceptions. These results are consistent with a role for CDKN2 and/or MTS2 in the pathogenesis of some lymphoid leukemia/lymphomas, particularly in T-ALL/lymphoblastic lymphoma.

Mutations in the coding region of c-MYC in AIDS-associated and other aggressive lymphomas.

Our previous studies of the translocated MYC gene in Burkitt's lymphoma showed the existence of clustered somatic mutations located in the transcriptional activation domain. We now report that aggressive lymphomas arising in the acquired immunodeficiency syndrome (AIDS) contain similar mutations and that the presence of mutations is correlated with the rearrangement of the oncogene. Mutations were also found in other de novo non-AIDS, non-Burkitt's aggressive lymphomas with MYC rearrangements. An unusual asparagine to serine mutation at codon 11 was identified in several transformed follicular lymphomas without MYC rearrangement but not in normal tissues from patients with this mutation. These findings indicate that AIDS-associated and other de novo aggressive lymphomas with the MYC gene rearrangement are subject to the same mutation and selection process that affects Burkitt's lymphomas.

Clustered mutations in the second exon of the MYC gene in sporadic Burkitt's lymphoma.

The primary tumors from 15 untreated patients with Burkitt's lymphoma were analysed for abnormalities in the coding region of the MYC gene by single stranded conformational polymorphism (SSCP) analysis followed by DNA sequencing. Fourteen of the 15 tumors had one or more clonal mutations. Forty one mutations were found in the second exon; only one occurred in the third exon. Seven tumors had mutations that clustered in a region spanning amino acids 38-63. Four of these possessed mutations that altered prolines at positions 57 (3), 60 (1), and 63 (1). Seven tumors were mutated in the central portions of the second exon. These occurred at position 95 (2), position 115 (2), position 137 (1), and position 138 (3). Analysis of the published sequences from five lymphoma cell lines and one primary tumor showed a similar clustering of mutations, with all six having mutations in codons between positions 38-63. The regions where mutations occurred have been associated with a variety of properties, including transcriptional activation and cellular transformation. The number and location of mutations showed no correlation with either chromosome 8 or chromosome 14 breakpoints or with the Epstein-Barr virus positivity of the tumors. This unexpected, frequent occurrence of clustered mutations in the second exon of the MYC gene suggests a role for the mutated MYC proteins in the pathogenesis of Burkitt's lymphoma, possibly through altered interactions of this domain with other cellular factors.

Mutation of the ras genes is a rare genetic event in the histologic transformation of follicular lymphoma.

The role of ras gene mutations in the progression of follicular lymphoma has been ascertained by SSCP-PCR and sequencing. A total of 40 transformed lymphomas were studied, 16 of which had a matched preceding low-grade biopsy. Only one transformed lymphoma was found to have a missense mutation at codon 12 of N-ras, resulting in an amino acid change of glycine to serine. We conclude that mutation within the ras gene family is a rare event in the transformation of follicular lymphoma.

Isolation of HIV-1 from plasma of infected individuals: an analysis of experimental conditions affecting successful virus propagation.

Experimental conditions affecting the successful propagation of HIV-1 from the plasma of seropositive individuals were examined. It was determined that whole blood samples collected with lithium heparin as the anticoagulant, immediate plasma separation, and immediate culturing were best suited for obtaining viable virus from plasma. Virus was isolated by infecting fresh phytohemagglutinin-stimulated normal donor peripheral blood mononuclear cells (PBMCs) with plasma followed by weekly cocultivation with new target cells. The plasma virus isolation rate was the greatest and HIV-1 titers were the highest for those individuals with less than 200 CD4+ cells/mm3 and decreased as the level of CD4+ cells approached normal values. We were able to obtain positive cultures from 29.5% of those patients with CD4+ counts greater than 500/mm3. HIV-1 titers in plasma also correlated with high serum p24 antigen levels when serum was treated with glycine to dissociate antigen-antibody complexes.

Reduction and release of ferritin iron by plant phenolics.

The reductive release of ferritin iron by several naturally occurring o-diphenols was studied. The initial rate of iron release was quantified by spectrophotometric measurement of the Fe(ferrozine)3(2+) complex, which absorbs maximally at 562 nm. The initial rate of iron release was dependent upon o-diphenol concentration, but not on the concentration of the chromophoric chelating agent, ferrozine, Stoichiometric measurements resulted in a ratio of 2Fe(II) released per molecule of o-diphenol. The series of o-diphenols studied included, caffeic acid, chlorogenic acid, dihydrocaffeic acid, 3,4-dihydroxybenzoic acid, and several analogs. These reductants represent an oxidation reduction potential range of 0.38 volts. A direct correlation between reducing power of the o-diphenols and rate of ferritin iron release was observed. Superoxide dismutase, catalase, mannitol, or general radical traps had no effect on the rate of iron removal; however, EDTA and oxalate inhibited iron release. A mechanism for ferritin iron reduction and release by o-diphenols consistent with the experimental observations is discussed.

Motor control in children and adults during a non-speech oral task.

Although decreased accuracy and increased variability of movement is a common developmental finding, the nature of these performance patterns remains poorly understood. The present study examined the accuracy and stability of several aspects of oral motor control. Specifically, we examined the control of absolute timing (temporal parameterization), absolute amplitude (amplitude parameterization), and relative timing and amplitude (generalized motor programs) in children and adults during a lip plus jaw opening and closing task. As was the case with similar reports, we found that children were both less accurate and less stable in their assignment of temporal and amplitude parameters. However, we further found that although children's underlying movement patterns were less accurate than those of adults, children exhibited similar variability in their generalized motor programs. The results are discussed within the framework of a schema model of motor control (Schmidt, 1975) with reference to the strategic allocation of resources during motor learning (e.g., Clark & Robin, 1998).

Analysis of carboxyhemoglobin and cyanide in blood from victims of the Dupont Plaza Hotel fire in Puerto Rico.

Ninety-seven people died from a fire that occurred in the Dupont Plaza Hotel in Puerto Rico on 31 Dec. 1986. All, except four who died later in the hospital, were found dead at the scene. All of the fatalities at the hotel (except for eight) were burned beyond recognition. Blood from seventy-eight of the victims was screened for carboxyhemoglobin at the Institute for Forensic Sciences in Puerto Rico and was then sent to the National Institute of Standards and Technology, Gaithersburg, Maryland, for analysis of carboxyhemoglobin and cyanide concentrations. The blood data indicated that carbon monoxide and hydrogen cyanide, singly or combined, were probably not responsible for the majority of the deaths that occurred in the badly burned victims. On the other hand, the significantly higher carboxyhemoglobin in the nonburned victims indicated that carbon monoxide alone or combined with hydrogen cyanide probably played a major role in the cause of their deaths.

The linkage that worked: the Catholic University of America/Carroll Manor Teaching Nursing Home Program.

The TNH at the CUA/CM site included a group of people who agreed to direct their mutual commitment to common goals; they operated within a shared belief system, agreed to model a liaison that would result in quality care for the elderly, and hoped to create interest in gerontological nursing by increasing the number of prepared gerontological nursing specialists. Four areas of clinical knowledge enabled the success of this project: practice, education, administration, and research. The elements of this one situation can be translated into criteria that guide the establishment and maintenance of a TNH, namely: Two critical ingredients: a nursing home and a school of nursing with an undergraduate and a graduate nursing program; A formal agreement that specifies; a shared mission statement; responsibilities in the school and in the nursing home for practice, education, administration, research, and consultation; Clearly defined roles for the nursing faculty in the nursing home, and for the professional nursing staff in the school of nursing; Opportunity for faculty and agency input into respective institutions at all levels, including the highest policy making level; and A steering committee with representation from the school of nursing and the nursing home that guides the functions of the teaching nursing home activities; Depending upon the circumstances, the environment, and the people, other persons may or may not be able to replicate this model. Whether or not replication is possible, there may be some aspects of this experience that will suggest positive avenues to explore with the hope of establishing collaboration linkages, between nursing education and nursing service.

The effects of interactive video on cognitive achievement and attitude toward learning.

The purpose of this experimentally designed study was to determine the effects of an interactive videodisc program, entitled "Diabetic Health Assessment," versus traditional lecture on cognitive learning and affective behaviors of baccalaureate nursing students. It was hypothesized that: 1) there would be no significant difference in the cognitive achievement scores between those students taught by an interactive videodisc program (experimental group) compared to those students taught by a traditional lecture method (control group), and 2) there would be a statistically significant difference in student attitude toward learning between those students taught by an interactive videodisc program compared to students taught by a traditional lecture method. Eighty-three third-year baccalaureate nursing students at a major urban university served as subjects and were randomly assigned to either a control (n = 41) or an experimental group (n = 42). The multivariate analysis of covariance with two criteria and the pretest as the covariate was significant (p = .000, df = 4, 140) indicating that the adjusted posttest scores on the two measures were significantly different for the experimental group compared to the control group. The univariate F for the cognitive measure was nonsignificant (p = .283, df = 2, 72) indicating that students' achievement under interactive video is not significantly different than under traditional lecture. The univariate F for the affective measure was significant (p = .000, df = 2, 72) indicating that the students learning by interactive video possessed a more positive attitude toward learning than those learning by traditional lecture method of instruction.

Predictors of hospital readmission among the elderly with congestive heart failure.

This study compared elderly patients with congestive heart failure discharged from home healthcare to the home vs. those rehospitalized. The rate of rehospitalization in this sample of 117 was 27%. Significant predictors of rehospitalization included number of home healthcare days, number of previous hospitalizations, and the services of a home health aide. Implications include the timing and nature of home health visits.

A clinical pathway for congestive heart failure.

This study has shown improved outcomes with the use of a clinical pathway. However, under PPS additional ways for coordination among healthcare providers and patients need to be developed to ensure improved care beyond those focusing on the use of the pathway. One recommendation is the use of telehealth.