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Biomedical subjects

W Silverman

Publications and source records attributed to W Silverman.

At least 19 recordsLinked to original sources
PubMed2001

Elevated plasma amyloid beta-peptide 1-42 and onset of dementia in adults with Down syndrome.

We compared levels of plasma amyloid beta-peptides Abeta1-42 and Abeta1-40 in 108 demented and nondemented adults with Down syndrome (DS) and 64 adults from the general population. Abeta1-42 and Abeta1-40 levels were significantly higher in adults with DS than in controls (P=0.0001). Compared to nondemented adults with DS, Abeta1-42 levels in demented adults with DS were selectively increased by 26% (28.2 pg/ml vs. 22.4 pg/ml, P=0.004). In addition, mean plasma levels of Abeta1-42 were 22% higher in DS cases with the apolipoprotein varepsilon4 allele than in DS subjects without an varepsilon4 allele (25.9 pg/ml vs. 21.2 pg/ml, P=0.01), while mean plasma levels of Abeta1-40 did not vary by APOE genotype. These results support the hypothesis that Abeta1-42 plays an important role in the pathogenesis of dementia associated with DS, as it does in Alzheimer's disease, and that variations in plasma levels may be related to disease progression.

Adult↗
PubMed2001

Representation and simulation of biochemical processes using the pi-calculus process algebra.

Despite the rapidly accumulating body of knowledge about protein networks, there is currently no convenient way of sharing and manipulation of such information. We suggest that a formal computer language for describing the biomolecular processes underlying protein networks is essential for rapid advancement in this field. We propose to model biomolecular processes by using the pi-Calculus, a process algebra, originally developed for describing computer processes. Our model for biochemical processes is mathematically well-defined, while remaining biologically faithful and transparent. It is amenable to computer simulation, analysis and formal verification. We have developed a computer simulation system, the PiFCP, for execution and analysis of pi-calculus programs. The system allows us to trace, debug and monitor the behavior of biochemical networks under various manipulations. We present a pi-calculus model for the RTK-MAPK signal transduction pathway, formally represent detailed molecular and biochemical information, and study it by various PiFCP simulations.

Biochemistry↗
PubMed1999

Continuous infusion cyclosporine and nifedipine to day +100 with short methotrexate and steroids as GVHD prophylaxis in unrelated donor transplants.

Unrelated donor marrow transplantation is associated with an increased incidence of graft-versus-host disease (GVHD) compared with sibling donor transplants. Forty-one patients undergoing unrelated donor transplants were treated with a GVHD prophylaxis regimen that consisted of continuous infusion cyclosporine from day -1 to 100 days post transplant along with nifedipine, glucocorticoids and short-course methotrexate. The regimen was well-tolerated in this cohort with mostly high risk disease. Fifty-one percent of patients developed acute GVHD, which was grade III-IV in 22% of patients. Six of 22 patients at risk for chronic GVHD developed extensive chronic GVHD, five of whom were adults. In patients <18 years of age, there was a >40% chance of 2 year disease-free survival. Use of continuous infusion cyclosporine with nifedipine as an immunosuppressant and protectant against cyclosporine-induced toxicities in unrelated donor transplants is well-tolerated, and results in acute GVHD incidence favorable to that reported with bolus cyclosporine.

Adolescent↗
PubMed1997

Gastrointestinal bleeding in cirrhotic patients with hepatocellular carcinoma undergoing intrahepatic artery chemotherapy.

BACKGROUND: Hepatocellular carcinoma in cirrhotic patients increases the risk of variceal bleeding. We sought to characterize bleeding in a cirrhotic patient population undergoing intrahepatic artery chemotherapy for hepatocellular carcinoma and to determine the possible influence of this treatment on gastrointestinal bleeding. METHODS: We retrospectively reviewed 179 patients with hepatocellular carcinoma who underwent intrahepatic artery doxorubicin and cis-platinum chemotherapy to determine the incidence of gastrointestinal bleeding and compared them with 434 hepatocellular carcinoma historic controls not undergoing regional chemotherapy. RESULTS: Of the 179 patients, 27 patients (15.1%) developed upper gastrointestinal bleeding over a mean follow-up of 15.2 months; 18 of the 27 (66.7%) bled from a variceal source and 9 (33.3%) bled from a nonvariceal source: ulcer (n = 6), gastropathy (n = 1), Mallory-Weiss (n = 1), erosive gastritis (n = 1). Twenty-one patients developed bleeding after initiation of chemotherapy (14 variceal and 7 nonvariceal). The number of chemotherapy sessions among patients with variceal and nonvariceal bleeding was similar (2.1 +/- 0.4 and 4.0 +/- 1.2; p = Not significant). Patients with variceal and nonvariceal bleeding were comparable with respect to Child-Pugh classification, pTNM stage, age, time to bleeding, and gender. CONCLUSIONS: Regional intra-arterial chemotherapy for hepatocellular carcinoma is associated with a low risk of variceal bleeding. Nonvariceal sources of upper gastrointestinal bleeding in this population account for a significant component of bleeding episodes.

Adolescent↗
PubMed1997

The epidemiology of Alzheimer disease in intellectual disability: results and recommendations from an international conference.

Among adults with intellectual disability, virtually everyone with Down's syndrome (DS) over the age of 40 years has neuropathology currently viewed to be consistent with a diagnosis of Alzheimer disease (AD), while other adults with intellectual disability without DS display an increased prevalence of Alzheimer-type neuropathology after they reach the age of 65. This paper presents the results of discussions by an epidemiology workgroup, formed at an international conference convened to discuss AD among people with intellectual disability, concerning: (1) the incidence and prevalence of clinical dementia in adults with intellectual disability; (2) risk factors for the development of AD in adults with intellectual disability; and (3) a minimum data set that would be of great utility for future research on AD in adults with intellectual disability.

Aged↗
PubMed1996

Prevalence of dementia in adults with and without Down syndrome.

Declines in adaptive behavior were examined in a study of dementia in adults with Down syndrome and other forms of mental retardation. No significant differences were found between adults under 50 years of age with and without Down syndrome. In contrast, individuals over 50 who had Down syndrome were more likely to be classified as having dementia over a range of quantitative decision criteria; nevertheless, prevalence estimates of dementia were substantially below the presumed 100% prevalence of neuropathological markers of Alzheimer disease. This apparent discrepancy between functional and neuropathological findings may be associated with variations in risk associated with Down syndrome genotypes and/or a true lack of correspondence between classical neuropathological hallmarks of Alzheimer disease in this population and clinical expression.

Adaptation, Psychological↗
PubMed1995

A comparison of nonionic versus ionic contrast media: results of a prospective, multicenter study. Midwest Pancreaticobiliary Study Group.

BACKGROUND: Pancreatitis is one of the most common complications associated with ERCP. Multiple factors have been implicated for this potentially serious complication. Numerous suggestions for minimizing risks at ERCP have been offered, one of which is to use nonionic, low osmolarity contrast agents for pancreatic injection. Results of previous studies comparing different contrast media have been inconclusive. METHODS: To evaluate the role contrast material plays in the development of post-ERCP pancreatitis, the Midwest Pancreaticobiliary Group performed a prospective double-blind controlled study. A total of 1,979 consecutive ERCP patients were enrolled, and 1,659 patients with pancreatic duct injections were divided into subgroups according to the complexity of the ERCP. Post-ERCP pancreatitis was compared between similar groups. Patients were randomized to receive injections of nonionic, low osmolarity contrast or standard ionic contrast media. RESULTS: The overall incidence of post-procedural pancreatitis was 10.2%. Those with diagnostic ERCP had the lowest incidence at 5.6%. Therapeutic procedures (12.3%) and sphincter of Oddi manometry (15.2%) had higher rates. Those injected with standard (ionic) contrast had an incidence of 10.4% and after injection with lower osmolar (nonionic) contrast, there was a 10% post-procedural pancreatitis rate. CONCLUSIONS: Patients with more complex procedures develop pancreatitis more frequently. The use of low osmolar (nonionic) contrast media does not decrease the incidence of post-ERCP pancreatitis.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1993

Alzheimer neuropathology in mentally retarded adults: statistical independence of regional amyloid plaque and neurofibrillary tangle densities.

The densities of neurofibrillary tangles (NFT) and neuritic plaques (NP) were assessed quantitatively in the brains of 303 mentally retarded adults 23 to 90 years of age at the time of their deaths (mean = 59.5 years). Cases with Down's syndrome, hydrocephalus and metabolic disorders were excluded from the study. Examinations of frontal, temporal, parietal, and occipital cortex, as well as hippocampus and parahippocampal gyrus were made in every case. NPs and/or NFTs were observed within the brains of 163 cases (53.8%). Detailed analyses indicated that NP density within all brain regions examined was positively related to age, with the largest age associated increases in density seen in frontal and temporal regions. In contrast, NFT density increased with age only within hippocampus and parahippocampal gyrus, but not neocortex. In addition, NP lesions within neocortex were more diffusely distributed across regions for older compared to younger cases, while no similar age-associated change in the topography of NFTs was observed. Finally, factor analyses of the combined NP and NFT data indicated that, while strong correlations existed across the various brain regions for measures of NP and NFT densities, considered separately, there was virtually no indication of regional associations between these two types of lesions. While these data, from cases with mental retardation, cannot be generalized directly to the nonretarded population, they provide strong evidence that models of Alzheimer pathogenesis must take into account the fact that regional densities of NPs and NFTs, and, therefore, the underlying processes associated with formation of these lesions, can be largely independent.

Adult↗
PubMed1990

Alzheimer neuropathology in non-Down's syndrome mentally retarded adults.

We examined the brains of 385 mentally retarded adults aged 23-90 years without Down's syndrome (DS), metabolic disorder, or hydrocephalus to extend our knowledge about the occurrence of Alzheimer-type neuropathology in this population. Relevant measures of neuropathology also were related to selected information available from clinical records. The presence of one or more neurofibrillary tangles (NFT) and/or neuritic plaques (NP) was observed in 63.4% of all cases and varied with age. The prevalence of positive cases was higher when mental retardation was due to head trauma, congenital malformation, or familial factors and when a history of seizures was reported. Comprehensive morphometric analyses of neocortical, hippocampal and parahippocampal areas indicated that recommended age-specific quantitative criteria for the diagnosis of Alzheimer disease [Khachaturian ZS (1985) Arch Neurol 42:1097-1105] were met in 9.5% of cases less than 50 years of age, 54.2% between 50 and 65, 70% between 66 and 75, and 87% of the cases greater than 75 years of age. However, a limited immunohistochemical study revealed that in most cases the NP did not have a neuritic component containing paired helical filaments and in this respect most of the plaques observed in this population may differ from those most strongly associated with Alzheimer disease. In addition, substantial numbers of NFT were seen in frontal cortex, contrasting with results reported in the literature for nonretarded populations. The number of NP per mm2 consistently increased with age for all areas examined, while the relationship between NFT density and age varied across areas, and was clearly not monotonic.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Specific motor abilities associated with speech fluency in Down's syndrome.

Eight adult male stutterers with Down's syndrome (DS) were compared with a matched group of fluent speakers with DS on verbal and manual motor production tasks at two levels of complexity. The simpler tasks involved diadochokinetic rate (syllable repetition) and finger tapping; the more complex tasks involved the imitation of sentences and placing pegs in the grooved pegboard. On both verbal and manual tasks, stutterers were faster on the simpler but slower on the more complex tasks than were the fluent speakers. The findings suggest that stutterers with DS have a different motor organization than fluent speakers with DS.

Adult↗
PubMed1990

Conversational analyses of males with fragile X, Down syndrome, and autism: comparison of the emergence of deviant language.

Deviant, repetitive language of 33 males (9 with Down syndrome, 12 with fragile X (fra[X]) syndrome, and 12 with autism) was analyzed within three conversational contexts: direct responses, initiation of new material, and topic maintenance. Results indicated that males with fra(X) manifest deviant, repetitive language that is distinct from males with either Down syndrome or autism. Thus, the deviant repetitive language of males with fra(X) cannot be accounted for by either their level of adaptive functioning or autistic-like behaviors per se. Possible explanations for this etiologically specific language deviance were discussed.

Adolescent↗