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Biomedical subjects

Donald A Young

Publications and source records attributed to Donald A Young.

10 recordsLinked to original sources
PubMed2007

Catechol-O-methyl transferase and expression of schizophrenia in 73 adults with 22q11 deletion syndrome.

BACKGROUND: Catechol-O-methyl transferase (COMT) is a candidate gene for schizophrenia with a role in dopamine metabolism, particularly in frontal cortex. COMT is within the region commonly deleted in 22q11 deletion syndrome (22q11DS), a syndrome with high prevalence of schizophrenia. We examined the role of COMT in schizophrenia-related expression in 22q11DS. METHODS: We genotyped the COMT functional Val(158/108)Met allele in 73 Caucasian adults with 22q11DS (36 men, 37 women; aged 33.8, SD 10.1 years; 37 Met, 36 Val hemizygosity) blind to clinical data and assessed effects on symptoms and frontal functioning. RESULTS: The lower activity Met allele was not significantly more prevalent than the Val allele in 33 subjects with schizophrenia. Excitement symptoms were more severe, however, and three frontal cognitive tests (theory of mind, Trails B, and olfactory identification), communication, and social functioning measures showed significantly worse performance with Met allele hemizygosity, even after accounting for effects of schizophrenia. CONCLUSIONS: The results suggest that hemizygosity of the COMT functional allele exerts an effect on some measures of frontal functioning in 22q11DS. Elevated levels of tonic dopamine activation associated with the COMT Met allele may underlie these aspects of expression. We must look elsewhere for causes of the high prevalence of schizophrenia in 22q11DS, however.

Adult↗
PubMed2006

Neurocognitive profile in 22q11 deletion syndrome and schizophrenia.

OBJECTIVE: Schizophrenia is associated with neurocognitive deficits, but its etiologic heterogeneity may complicate the delineation of a neurocognitive profile. Schizophrenia associated with 22q11 Deletion Syndrome (22qDS) represents a more genetically homogeneous subtype for study. We hypothesized that in adults with 22qDS the neurocognitive profiles would differ between those with and without schizophrenia. METHOD: Using a comprehensive battery of tests, we compared the neurocognitive performance profiles in those with schizophrenia (n=27; 14 M, 13 F; mean age=30.6 years, SD=7.7 years) and those with no history of psychosis (n=29; 16 M, 13 F; mean age=25.0 years, SD=9.0 years). RESULTS: The 22qDS groups with and without schizophrenia had similar mean estimated IQ (71.6, SD=8.2 and 74.8, SD=6.1, respectively) and academic achievement, however the neurocognitive profiles of the two groups differed significantly on multivariate analysis (F(24,31)=2.25, p=0.017). The group with schizophrenia performed significantly more poorly on tests of motor skills, verbal learning, and social cognition (effect sizes>or=0.8) after correction for multiple comparisons. Other tests, but not the attentional measures used, showed nominally significant differences. CONCLUSIONS: In adults with 22qDS, the pattern of neurocognitive differences between those with and without schizophrenia appears similar to that between patients with schizophrenia and controls. Attentional dysfunction may be a more general feature of 22qDS. The findings support 22qDS-schizophrenia as a genetic model for neurodevelopmental investigations of schizophrenia.

Adult↗
PubMed2005

Thymoma arising within cardiac myxoma.

Hematopoietic, glandular, and mesenchymal elements can be found within cardiac myxomas; ectopic endocrine tissues and "thymic rests" have also rarely been described. Atrial tumors (one right and one left) from 2 patients (a 69-year-old man and a 77-year-old woman) were encountered among the atrial myxoma cases in one of the author's consultation files. Both tumors were comprised of classic cardiac myxoma (with characteristic rings and syncytial chains of myxoma cells in a loose myxoid matrix) and cellular thymoma-like elements (characterized by a lobulated sheet-like growth of epithelioid spindle cells admixed with small lymphocytes punctuated by vessels with prominent perivascular spaces). Neither patient had evidence of thymoma elsewhere. Immunophenotypically, the thymoma-like component reacted strongly with antibodies to keratins (AE1/AE3, Cam 5.2, wide spectrum, CK19, CK7) and CD57 and weakly with antibodies to CD31, CD34, and calretinin. This intermediate phenotypic expression of both epithelial and vascular antigens likely reflects the multipotential nature of the cells comprising this lesion. The most likely explanation for this extremely unusual finding is neoplastic transformation of thymic rests within a myxoma.

Aged↗
PubMed2003

A comparison between an interview and a self-report method of insight assessment in chronic schizophrenia.

We examined the relationship between a researcher-rated and a self-report method of insight assessment in patients with schizophrenia. Previous research has established that a moderate correlation exists between several researcher-rated and self-report insight scales. Hence, we wanted to investigate this association using another combination of assessment techniques. Accordingly, 34 patients with chronic schizophrenia were administered the Scale to Assess Unawareness of Mental Disorder (SUMD) and the Birchwood self-report Insight Scale (IS). We found a significantly lower report of insight on the Birchwood IS, regardless of administration order. These findings suggest that inherent bias within the patient-examiner interaction may be responsible for this discrepancy. Overall, a significant positive correlation was observed between total scores on the SUMD and the Birchwood self-report IS. Unexpectedly, there was a remarkable difference in correlation with respect to the order of test administration. The "self-report first" group's scores were strongly correlated, whereas the "researcher-rated first" group's scores showed little relation. These results demonstrate the importance of investigating the effects of administration order, and also question the reliability of other correlational studies between researcher-rated and self-report insight scales that have failed to employ a counterbalanced research design.

Adult↗
PubMed2003

Neuropsychological differentiation of late-onset schizophrenia and dementia of the Alzheimer's type.

Late-onset schizophrenia and dementia of the Alzheimer's type (DAT) often present with some pathological and behavioral commonalities. Specifically, both illnesses may involve varying degrees of delusional manifestation, apathy, lateral/third-ventricular enlargement, reduced frontal lobe activity, and hippocampal atrophy. Moreover, patients with either disease have shown comparable cognitive impairment on standardized neuropsychological tests. As such, a differential diagnosis of the 2 disorders on the basis of such testing can prove to be difficult. This study evaluated the neuropsychological test results of 32 patients with late-onset schizophrenia and 32 patients with DAT to distinguish the tests that best differentiate the 2 disorders. Results indicate that the Wechsler Adult Intelligence Scale-Revised Similarities subtest and the California Verbal Learning Test (both short- and long-delay free recall) correspond to sensitive diagnostic neuropsychological measures. This investigation was preliminary in nature, and should aid in the development of a definitive differential profile.

Age of Onset↗
PubMed2002

Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair.

Preclinical and clinical studies suggest a possible role for cyclooxygenases in bone repair and create concerns about the use of nonsteroidal antiinflammatory drugs in patients with skeletal injury. We utilized wild-type, COX-1(-/-), and COX-2(-/-) mice to demonstrate that COX-2 plays an essential role in both endochondral and intramembranous bone formation during skeletal repair. The healing of stabilized tibia fractures was significantly delayed in COX-2(-/-) mice compared with COX-1(-/-) and wild-type controls. The histology was characterized by a persistence of undifferentiated mesenchyme and a marked reduction in osteoblastogenesis that resulted in a high incidence of fibrous nonunion in the COX-2(-/-) mice. Similarly, intramembranous bone formation on the calvaria was reduced 60% in COX-2(-/-) mice following in vivo injection of FGF-1 compared with either COX-1(-/-) or wild-type mice. To elucidate the mechanism involved in reduced bone formation, osteoblastogenesis was studied in bone marrow stromal cell cultures obtained from COX-2(-/-) and wild-type mice. Bone nodule formation was reduced 50% in COX-2(-/-) mice. The defect in osteogenesis was completely rescued by addition of prostaglandin E2 (PGE(2)) to the cultures. In the presence of bone morphogenetic protein (BMP-2), bone nodule formation was enhanced to a similar level above that observed with PGE(2) alone in both control and COX-2(-/-) cultures, indicating that BMPs complement COX-2 deficiency and are downstream of prostaglandins. Furthermore, we found that the defect in COX-2(-/-) cultures correlated with significantly reduced levels of cbfa1 and osterix, two genes necessary for bone formation. Addition of PGE(2) rescued this defect, while BMP-2 enhanced cbfa1 and osterix in both COX-2(-/-) and wild-type cultures. Finally, the effects of these agents were additive, indicating that COX-2 is involved in maximal induction of osteogenesis. These results provide a model whereby COX-2 regulates the induction of cbfa1 and osterix to mediate normal skeletal repair.

Animals↗
PubMed2002

Attentional processes in abstinent methylenedioxymethamphetamine (ecstasy) users.

In recent years, methylenedioxymethamphetamine (MDMA or ecstasy) has gained great popularity among young adults. Although human research in abstinent users has focused primarily on memory function, little attention has been given to other neuropsychological functions that may have some bearing on memory performance, such as attention. Hence, the purpose of this study was to examine the effects of MDMA on attentional processes. Accordingly, 24 MDMA users and 30 matched normal controls were tested on the Wechsler Abbreviated Scale of Intelligence (WASI) and the Test of Everyday Attention (TEA). We found MDMA users to show generally no significant difference on attention tasks compared with controls with the exception of a single TEA subtest. More interestingly, we found some preliminary evidence to indicate that dosage, in terms of the number of tablets used, may be related to impairment on specific component attentional tasks. This finding brings to light the important relationship between poor attentional processes and drug-taking behaviors and their reciprocal relationship.

Adult↗
PubMedDate not supplied

Expanding coverage: maintain a role for the individual market.

When most Americans think about health insurance, their frame of reference is employer- or government-sponsored health plans. But individual health insurance differs from these models. Most importantly, while individual insurance provides protection against unexpected medical expenses, it is limited in its ability to subsidize the expenses of people who already have serious health conditions when they enter the market. Nevertheless, it remains a vital part of our health care system, protecting millions of Americans against unexpected expenses at lower premium levels than many might assume.

Adolescent↗