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Biomedical subjects

R N Bryan

Publications and source records attributed to R N Bryan.

At least 37 records · Page 2Linked to original sources
PubMed1998

Sex differences in brain aging: a quantitative magnetic resonance imaging study.

BACKGROUND: Little is known about the effect of sex on age-related changes in brain structure. METHODS: Quantitative magnetic resonance imaging of the brain was performed in 330 elderly (age range, 66-96 years) volunteers living independently in the community, all of whom were participants in the Cardiovascular Health Study. Blinded measurements of global and regional brain size were made from T1-weighted axial images by means of computer-assisted edge detection and trace methods. High measurement reliabilities were obtained. RESULTS: Age-specific changes in brain size were significantly greater in men than women for the peripheral (sulcal) cerebrospinal fluid volume, the lateral (sylvian) fissure cerebrospinal fluid volume, and the parieto-occipital region area. Main effects of age were observed for all the remaining brain regions examined (cerebral hemisphere volume, frontal region area, temporoparietal region area, lateral ventricular volume, and third ventricle volume), but these effects were similar in men and women. Asymmetries in brain structures were not affected by aging in either sex. CONCLUSIONS: Our results are generally consistent with the few published studies on sex differences in brain aging and suggest that, for at least some structures, aging effects may be more apparent in men than women. The neurobiological bases and functional correlates of these sex differences require further investigation.

Age Distribution↗
PubMed1998

Craniocerebral magnetic resonance imaging measurement and findings in Lesch-Nyhan syndrome.

OBJECTIVE: To provide the first comprehensive magnetic resonance imaging (MRI) assessment of brain in a series of patients with Lesch-Nyhan syndrome (LNS), with emphasis on basal ganglia measurements. DESIGN: Routine readings of MRI studies, repeated reading in random order blinded to subject diagnosis, and 3-dimensional volumetric measures of basal ganglia regions. SETTING: The Johns Hopkins Hospital, Baltimore, Md. PATIENTS: Seven patients with LNS who have hypoxanthine guanine phosphoribosyltransferase levels less than 1.6% and characteristic clinical features of the disorder, which include hyperuricemia, cognitive impairment, and dystonic movement disorder, were compared with 7 age-matched control subjects. Five of the 7 patients demonstrated self-injurious behavior. MRI studies were performed using general anesthesia because of the severity of the movement disorder. MAIN OUTCOME MEASURES: Measurement of brain regions from MRI-obtained images. RESULTS: Routine readings described mild cerebral atrophy in 2 of 7 patients, but no caudate or putamen abnormalities were reported. However, on the directed blinded rereading, small caudates were suspected in 5 of 7 cases, and abnormalities in cerebral size and cranium were identified. Volumetric studies of the patients with LNS confirmed a 34% decrease in caudate volume (P<.001), a 17% decrease in total cerebral volume (P<.03), and a 12% decrease in putamen volume (P=.19). CONCLUSIONS: To our knowledge, this is the first demonstration of consistent neuroanatomic abnormalities in LNS. The findings of reduced basal ganglia volume are consistent with the dystonic movement disorder.

Adult↗
PubMed1998

bcl-2 antisense therapy chemosensitizes human melanoma in SCID mice.

Malignant melanoma is a prime example of cancers that respond poorly to various treatment modalities including chemotherapy. A number of chemotherapeutic agents have been shown recently to act by inducing apoptosis, a type of cell death antagonized by the bcl-2 gene. Human melanoma expresses Bcl-2 in up to 90% of all cases. In the present study we demonstrate that bcl-2 antisense oligonucleotide treatment improves the chemosensitivity of human melanoma grown in severe combined immunodeficient (SCID) mice. Our findings suggest that reduction of Bcl-2 in melanoma, and possibly also in a variety of other tumors, may be a novel and rational approach to improve chemosensitivity and treatment outcome.

Actins↗
PubMed1998

Premorbid prevalence of ADHD and development of secondary ADHD after closed head injury.

OBJECTIVE: To determine premorbid prevalence of attention-deficit hyperactivity disorder (ADHD) in children with moderate and severe closed head injury (CHI), to determine incidence of ADHD 1 year after injury, and to characterize children who develop ADHD by demographic, neuropsychiatric, and outcome variables. METHOD: Ninety-nine children who had severe and moderate CHI were followed up for 1 year. Premorbid and 1-year postinjury psychiatric status were ascertained by parent and child structured interviews and questionnaires measuring affective lability, aggression, apathy, and social judgment. RESULTS: Premorbid prevalence of ADHD was 0.20, significantly higher than in a reference population (0.045). Fifteen of the remaining 80 children (0.19) developed full ADHD criteria (except for age of onset) by the end of the first year. Children who developed secondary ADHD (S-ADHD) had significantly greater premorbid psychosocial adversity, posttraumatic affective lability and aggression, posttraumatic psychiatric comorbidity, and overall disability than children who did not develop S-ADHD. CONCLUSIONS: There is an excess prevalence of premorbid ADHD among children who present with moderate and severe CHI. Children with high psychosocial adversity are more likely to develop S-ADHD after CHI. S-ADHD has criteria in common with personality change due to CHI, a deficit in behavioral inhibition being the major overlapping feature.

Adolescent↗
PubMed1997

Patient characteristics associated with diagnostic imaging evaluation of persistent low back problems.

STUDY DESIGN: Post hoc analysis of data from the National Low Back Pain Study, a prospective observational multicenter study of patients referred for the evaluation and treatment of persistent low back problems. OBJECTIVE: To identify patient characteristics associated with use of particular diagnostic imaging examinations in patients with persistent low back problems. SUMMARY OF BACKGROUND DATA: The Agency for Health Care Policy and Research clinical practice guidelines on low back problems suggest that the use of particular diagnostic imaging tests for a given patient should be based on specific characteristics of that patient. METHODS: Use of diagnostic imaging examinations in 2,374 patients with persistent low back problems who were enrolled in the National Low Back Pain Study from 1986 to 1991 was analyzed. Stepwise logistic regression was used to identify patient characteristics that distinguish between enrollees who underwent particular imaging studies. RESULTS: Characteristics that distinguished patients who had undergone magnetic resonance imaging from those who had received only lumbo-sacral spine radiographs included higher socioeconomic status, greater resource use in the preceding 12 months, more functional impairment, presence of sciatica, and presence of neurologic signs/symptoms suggestive of nerve root compromise. Suspected soft tissue involvement was characteristic of enrollees who had undergone magnetic resonance imaging, whereas suspected structural involvement characterized patients who received noncontrast computed tomography. Only nonclinical factors, such as higher annual household income, disability compensation, and male gender distinguished enrollees who had undergone both magnetic resonance imaging and computed tomography-myelography from those who received only computed tomography-myelography. CONCLUSION: Particular patient socioeconomic and clinical characteristics are associated with receipt of specific imaging studies in evaluation of persistent low back problems.

Adult↗
PubMed1997

Multiple brain atlas database and atlas-based neuroimaging system.

For the purpose of developing multiple, complementary, fully labeled electronic brain atlases and an atlas-based neuroimaging system for analysis, quantification, and real-time manipulation of cerebral structures in two and three dimensions, we have digitized, enhanced, segmented, and labeled the following print brain atlases: Co-Planar Stereotaxic Atlas of the Human Brain by Talairach and Tournoux, Atlas for Stereotaxy of the Human Brain by Schaltenbrand and Wahren, Referentially Oriented Cerebral MRI Anatomy by Talairach and Tournoux, and Atlas of the Cerebral Sulci by Ono, Kubik, and Abernathey. Three-dimensional extensions of these atlases have been developed as well. All two- and three-dimensional atlases are mutually preregistered and may be interactively registered with an actual patient's data. An atlas-based neuroimaging system has been developed that provides support for reformatting, registration, visualization, navigation, image processing, and quantification of clinical data. The anatomical index contains about 1,000 structures and over 400 sulcal patterns. Several new applications of the brain atlas database also have been developed, supported by various technologies such as virtual reality, the Internet, and electronic publishing. Fusion of information from multiple atlases assists the user in comprehensively understanding brain structures and identifying and quantifying anatomical regions in clinical data. The multiple brain atlas database and atlas-based neuroimaging system have substantial potential impact in stereotactic neurosurgery and radiotherapy by assisting in visualization and real-time manipulation in three dimensions of anatomical structures, in quantitative neuroradiology by allowing interactive analysis of clinical data, in three-dimensional neuroeducation, and in brain function studies.

Anatomy, Artistic↗
PubMed1997

Description of the intrafollicular delivery of large molecular weight molecules to follicles of human scalp skin in vitro.

The objective of this study was to ascertain the elements that govern the intrafollicular delivery of large molecules to follicles of human scalp skin in vitro. The experiments were designed to assess the intrafollicular disposition of drug as a function of size, charge, and formulation. First, fluorescein covalently linked to antisense oligonucleotides and rhodamine-conjugated dextrans were topically applied to fresh human scalp skin in vitro. The drug position in the follicle was qualitatively determined by examining histologic sections of hair-bearing skin taken parallel to the skin surface at various depths and dissected hair follicles via fluorescent microscopy. Using radiolabeled antisense oligonucleotides we demonstrated that these cross sections can also be used to quantitatively localize the intrafollicular delivery of large molecules to follicles of human scalp skin in vitro. Experimental results showed that cationic lipid-based formulations enhanced delivery of oligonucleotides within the follicle. The qualitative analysis also illustrated that cationic lipid-based formulations directed the intrafollicular permeation along the junction of the internal and external root sheath. The charged, lower molecular weight (MW) dextrans permeated into all components of the hair follicle, including the hair shaft. The higher MW dextrans were confined to the follicular structures immediately surrounding the hair shaft. The demonstration of quantitation showed that approximately 0.5% of the applied dose was delivered to the hair bulbs and the deeper skin strata within 24 h of a single application. We conclude that topically applied agents of relatively large MW, in properly formulated delivery vehicles; have the potential to reach pharmacologically active concentrations at the hair bulb. It also should be noted that delivery takes place via the junction of the internal and external root sheath.

Dextrans↗
PubMed1997

Sulcal, ventricular, and white matter changes at MR imaging in the aging brain: data from the cardiovascular health study.

PURPOSE: To determine the distribution of changes in sulcal size, ventricular size, and white matter signal intensity depicted on cranial magnetic resonance (MR) images, with stratification according to age, race, and sex. MATERIALS AND METHODS: Ventricular size, sulcal size, and white matter signal intensity changes were graded on cranial MR images of 3,660 community-living, elderly participants in the Cardiovascular Health Study. A healthier subgroup was also defined. Summary statistics for both groups were generated for age, race, and sex. RESULTS: Regression models of the entire imaged cohort showed higher grades of all variables with increasing age, and higher ventricular and sulcal grades in men and in nonblack individuals. White matter grade was greater in women and in black individuals. Regression models of the healthier subgroup showed similar associations, except for a lack of association of sulcal and ventricular size with race. CONCLUSION: Sulcal width, ventricular size, and white matter signal intensity change with age, sex, and race. Knowledge of these changes is important in appropriate interpretation of MR images of the elderly.

Aged↗
PubMed1997

Infarctlike lesions in the brain: prevalence and anatomic characteristics at MR imaging of the elderly--data from the Cardiovascular Health Study.

PURPOSE: To determine the prevalence and anatomic characteristics of infarctlike lesions seen on cranial magnetic resonance (MR) images. MATERIALS AND METHODS: The study cohort consisted of 5,888 community-living individuals aged 65 years and older enrolled in a longitudinal, population-based study of cardiovascular disease. MR images were obtained from 3,658 participants and evaluated by trained readers. Lesion size, anatomic location, and signal intensity were recorded. Infarctlike lesion was defined as a nonmass, hyperintense region on spin-density- and T2-weighted images and, in cerebral white matter and brain stem, a hypointense region on T1-weighted images. RESULTS: Infarctlike lesions were depicted on MR images of 1,323 (36%) participants. Eighty-five percent (1,128 participants) had lesions 3 mm or larger in maximum dimension, although 70.9% (1,320 of 1,861) of these lesions were 10 mm or less. Lesion prevalence increased with age, especially with lesions 3 mm or larger, which increased from 22.1% (86 of 389) in the 65-69-year age group to 42.9% (88 of 205) in the over-85-year age group (P < .0001). Lesion prevalence was slightly greater in men (497 of 1,527 [32.5%]) than in women (631 of 2,131 [29.6%]), but did not differ between blacks and non-blacks. The deep nuclei were the most commonly affected anatomic sites, with 78.2% (1,451 of 1,856) of lesions. Lesions that involved the cerebrum and posterior fossa accounted for 11.7% (218 of 1,856) and 10.1% (187 of 1,856) of lesions, respectively. CONCLUSION: If the lesions reported in this study indicate cerebrovascular disease, subclinical disease may be more prevalent than clinical disease, and the prevalence of disease may rise with age. Also, infarctlike lesions have a distinctive anatomic profile.

Aged↗
PubMed1997

Trends in diagnostic imaging for low back pain: has MR imaging been a substitute or add-on?

PURPOSE: To assess whether magnetic resonance (MR) imaging has replaced other diagnostic imaging modalities in the evaluation of persistent low back pain. MATERIALS AND METHODS: Data on diagnostic imaging use in 2,374 adult patients with persistent low back pain in 1987-1990 were analyzed. Multiple logistic regression was used to estimate the annual adjusted odds of lumbosacral spine radiography, MR imaging, unenhanced computed tomography (CT), or CT myelography use. The national cost of diagnostic imaging for persistent low back pain in 1990 relative to 1987 was estimated. RESULTS: The adjusted odds of performing MR imaging in 1990 relative to 1987 was 3.44 (95% confidence interval, 2.63, 4.51), which reflects an estimated increase from 22 studies per 100 enrollees in 1987 to 75 studies per 100 enrollees in 1990. Use of MR imaging in combination with radiography, unenhanced CT, or CT myelography increased. The additional national cost of diagnostic imaging for persistent low back pain in 1990 relative to 1987 was estimated at $70-$176 million. CONCLUSION: MR imaging was used primarily as an add-on rather than a substitute for other imaging modalities in the evaluation of persistent low back pain. Thus, the volume and cost of diagnostic imaging for persistent low back pain have increased.

Adult↗
PubMed1997

Persistent low back pain in patients suspected of having herniated nucleus pulposus: radiologic predictors of functional outcome--implications for treatment selection.

PURPOSE: To assess the relationship between imaging findings, therapy, and functional outcome in patients with persistent low back pain who are suspected of having herniated nucleus pulposus. MATERIALS AND METHODS: Data collected during a multicenter, longitudinal study were retrospectively analyzed (n = 1,084). Multivariate regression was used to determine the association between imaging findings, therapy, and functional outcome. The patient outcome measure was disability days: the number of days the patient was unable to perform work-related activities. RESULTS: In patients with at least one normal advanced (imaging other than plain radiography) diagnostic study or with an unconfirmed diagnosis of herniated nucleus pulposus, outcome at 2-year follow-up was no better in patients who were treated than in those who were not. In patients with only abnormal advanced imaging results or with a concordant diagnosis based on clinical and imaging findings, outcome was better in patients who underwent surgery than in those treated nonsurgically. Patients with a free fragment, protrusion, or extrusion that was treated surgically had fewer disability days than patients treated nonsurgically. CONCLUSION: Advanced diagnostic imaging studies can play an important role in treatment selection in patients with persistent low back pain who are suspected of having herniated nucleus pulposus.

Absenteeism↗
PubMed1997

Absolute quantitation of diffusion constants in human stroke.

BACKGROUND AND PURPOSE: Animal studies have shown that MR diffusion imaging can outline acute ischemic regions before irreversible damage (infarction) occurs. To study evolution of ischemic lesions in humans, it is therefore important to quantify absolute diffusion constants (D values), but quantitation has not been reproducible among different clinics. These problems are explained, and a method for reproducible quantitation is suggested. METHODS: Diffusion-weighted and absolute diffusion images were acquired, and the absolute apparent diffusion constants in three orthogonal spatial directions (Dxx, Dyy, and Dzz) were measured. These were combined to calculate images of the orientation-independent apparent diffusion parameter Dav = 1/3 Trace[D] = 1/3(Dxx + Dyy + Dzz). Values of the individual diffusion constants and Dav were evaluated in 6 patients and 6 normal volunteers. RESULTS: Patient data show that comparison of diffusion constants between contralateral and ipsilateral hemispheres after ischemia may give results varying by more than 100% depending on orientation. Findings in normal-appearing regions containing a mixture of gray and white matter in patients (n = 5) and in normal volunteers (n = 6) show that Dav = (0.92+/-0.11) x 10(-3) mm2/s, with a small intersubject variation, whereas Dxx, Dyy, and Dzz vary strongly. Hemispheric ratios (ipsilateral/contralateral [I/C]) in these subjects were (I/C)Dav = 1.00+/-0.05, (I/C)Dxx = 1.02+/-0.15, (I/C)Dyy = 1.07+/-0.24, and (I/C)Dzz = 0.96+/-0.28. The individual subjects in this group all had an (I/C)Dav within 10% of unity, while the other three ratios showed intersubject variations as large as 100%. CONCLUSIONS: (I/C)Dav ratios are a reliable means to quantitate changes in absolute diffusion constants for the study of stroke evolution independent of tissue orientation, gradient orientation, and diffusion time. The use of these ratios will enable reproducible intersubject and interclinic quantitation.

Acute Disease↗