Biomedical subjects

D Norman

Publications and source records attributed to D Norman.

At least 37 records · Page 2Linked to original sources

PubMed2001

Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer's disease.

OBJECTIVES: To explore volume changes of the entorhinal cortex (ERC) and hippocampus in mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared with normal cognition (NC); to determine the powers of the ERC and the hippocampus for discrimination between these groups. METHODS: This study included 40 subjects with NC, 36 patients with MCI, and 29 patients with AD. Volumes of the ERC and hippocampus were manually measured based on coronal T1 weighted MR images. Global cerebral changes were assessed using semiautomatic image segmentation. RESULTS: Both ERC and hippocampal volumes were reduced in MCI (ERC 13%, hippocampus 11%, p<0.05) and AD (ERC 39%, hippocampus 27%, p<0.01) compared with NC. Furthermore, AD showed greater volume losses in the ERC than in the hippocampus (p<0.01). In addition, AD and MCI also had cortical grey matter loss (p< 0.01) and ventricular enlargement (p<0.01) when compared with NC. There was a significant correlation between ERC and hippocampal volumes in MCI and AD (both p<0.001), but not in NC. Using ERC and hippocampus together improved discrimination between AD and CN but did not improve discrimination between MCI and NC. The ERC was better than the hippocampus for distinguishing MCI from AD. In addition, loss of cortical grey matter significantly contributed to the hippocampus for discriminating MCI and AD from NC. CONCLUSIONS: Volume reductions in the ERC and hippocampus may be early signs of AD pathology that can be measured using MRI.

Aged↗

PubMed2001

Temporal lobe epilepsy: qualitative reading of 1H MR spectroscopic images for presurgical evaluation.

PURPOSE: To study the feasibility and clinical potential of visual inspection of hydrogen 1 magnetic resonance (MR) spectroscopic metabolite images for the lateralization of unilateral nonlesional temporal lobe epilepsy (TLE). MATERIALS AND METHODS: MR imaging and 1H MR spectroscopic imaging were performed of the temporal lobes in 50 patients with TLE and 23 age-matched healthy volunteers. N-acetylaspartate (NAA) and creatine plus choline metabolite images were read by two neuroradiologists who determined lateralization according to the side of lower NAA signal intensity. Quantitative estimates of NAA were calculated by using an automated fitting program. RESULTS: Agreement in lateralization between readers was significant with a kappa score of 0.53 for all patients with TLE and 0.63 for patients displaying mild or marked NAA asymmetry. Among the 50 patients with TLE, lateralization was determined correctly by reader 1 in 38 (76%) patients and by reader 2 in 31 (62%) patients. If limited to patients with mild or marked NAA asymmetry, correct lateralization improved to 30 (77%) of 39 and 16 (80%) of 20 patients, respectively. Combined qualitative reading and quantitative spectral fitting enabled lateralization in 34 (85%) of 40 patients with TLE for reader 1 and 30 (77%) of 39 for reader 2, including nine of 14 patients with TLE with negative MR images. CONCLUSION: Reading of metabolite images is a feasible and fast means for noninvasive evaluation of patients with TLE who are candidates for surgery and enables lateralization in some patients with negative MR images.

Adult↗

PubMed2001

Effects of non-weight bearing and hyperbaric oxygen therapy in vascular deprivation-induced osteonecrosis of the rat femoral head.

We examined the role of hyperbaric oxygenation (HBO2) combined with non-weight bearing (NWB) in the treatment of vascular deprivation-induced osteonecrosis of the femoral head in the rat. Group 1 included 16 rats treated by a combination of NWB and HBO2. Twenty animals treated by NWB alone (group 2), and 18 rats which received no treatment (group 3), served as the control groups. Maximal benefit of HBO2 was observed on Day 30 of the study. The femoral heads were less deformed in group 1 animals (P = 0.07). Preservation of the femoral heads was observed in a larger proportion of the HBO2-treated animals (P = 0.06). A smaller proportion of high-grade new bone formation was observed, and more animals demonstrated well-regenerated hematopoietic tissue (P = 0.08). The tendency for less deformation of the femoral head in the HBO2-treated group might be a predictor of better function of the hipjoint.

Animals↗

PubMed2000

Hippocampal and cortical atrophy predict dementia in subcortical ischemic vascular disease.

BACKGROUND: The cause of dementia in subcortical ischemic vascular disease (SIVD) is controversial. OBJECTIVES: To determine whether cognitive impairment in SIVD 1) correlates with measures of ischemic brain injury or brain atrophy, and/or 2) is due to concomitant AD. METHODS: Volumetric MRI of the brain was performed in 1) elderly subjects with lacunes (L) and a spectrum of cognitive impairment-normal cognition (NC+L, n = 32), mild cognitive impairment (CI+L, n = 26), and dementia (D+L, n = 29); 2) a comparison group with probable AD (n = 28); and 3) a control group with normal cognition and no lacunes (NC). The authors examined the relationship between the severity of cognitive impairment and 1) volume, number, and location of lacunes; 2) volume of white matter signal hyperintensities (WMSH); and 3) measures of brain atrophy (i. e., hippocampal, cortical gray matter, and CSF volumes). RESULTS: Among the three lacune groups, severity of cognitive impairment correlated with atrophy of the hippocampus and cortical gray matter, but not with any lacune measure. Although hippocampal atrophy was the best predictor of severity of cognitive impairment, there was evidence for a second, partially independent, atrophic process associated with ventricular dilation, cortical gray matter atrophy, and increase in WMSH. Eight autopsied SIVD cases showed variable severity of ischemic and neurofibrillary degeneration in the hippocampus, but no significant AD pathology in neocortex. The probable AD group gave evidence of only one atrophic process, reflected in the severity of hippocampal atrophy. Comparison of regional neocortical gray matter volumes showed sparing of the primary motor and visual cortices in the probable AD group, but relatively uniform atrophy in the D+L group. CONCLUSIONS: Dementia in SIVD, as in AD, correlates best with hippocampal and cortical atrophy, rather than any measure of lacunes. In SIVD, unlike AD, there is evidence for partial independence between these two atrophic processes. Hippocampal atrophy may result from a mixture of ischemic and degenerative pathologies. The cause of diffuse cortical atrophy is not known, but may be partially indexed by the severity of WMSH.

Aged↗

PubMed2000

The effect of conversion from cyclosporine to tacrolimus on gingival hyperplasia, hirsutism and cholesterol.

UNLABELLED: The use of cyclosporine for immunosuppression in renal transplantation allograft recipients is associated with hypertrichosis, gingival hyperplasia, and hypercholesterolemia. Conversion of patients to tacrolimus may lead to an improvement in these effects with minimal risk of rejection or allograft dysfunction. METHODS: Sixteen renal transplant recipients were prospectively converted from CsA to tacrolimus and followed for 1 year. Gingival hyperplasia index, total cholesterol, and blood pressure were recorded at the outset, 4-, 8-, and 12-month intervals. Glomerular filtration rate was checked before conversion and 1 year later. Photographs documenting hypertrichosis were taken before conversion and 1 year later. Adverse effects from tacrolimus were recorded at 4, 8, and 12 months. RESULTS: Twelve patients with hypertrichosis noted rapid improvement. Mean gingival hyperplasia index decreased from 24 to 6; mean total cholesterol decreased from 237 to 195. Glomerular filtration rate was essentially unchanged (56 to 54). One episode of rejection occurred, three patients developed diarrhea, three noted headaches, and one had a tremor. CONCLUSION: If carefully monitored, patients suffering adverse effects secondary to cyclosporine may be converted to tacrolimus with minimal risk of allograft dysfunction or rejection.

Adolescent↗

PubMed2000

Intravenous mycophenolate mofetil: safety, tolerability, and pharmacokinetics.

An intravenous (i.v.) formulation of mycophenolate mofetil (MMF; CellCept, Roche Pharmaceuticals, Inc., Palo Alto, CA) that will enable its administration to patients unable to tolerate oral medication is available. Two separate studies, an open-labeled pharmacokinetic (PK) study and a double-blind safety study, were performed. Within 24 h after transplant, 153 (safety study) and 45 (PK study) first or second renal transplant recipients were started on i.v. MMF 1 g Q12h or placebo (used in the safety study only, 2:1 MMF:placebo), given over 2 h via a dedicated peripheral venous catheter. In the safety study, per os (p.o.) MMF (1g Q12h) or placebo was administered, starting within 72 h after transplant, whereas in the PK study, p.o. MMF was started on the evening of day 5. Sequential blood samples obtained on study days 5 (i.v. MMF) and 6 (p.o. MMF) before and up to 12 h after the AM dose were analyzed for mycophenolic acid (MPA) and MPA glucuronide (MPAG) concentrations by high-performance liquid chromatography. The area under the concentration curve (AUC) was calculated using the linear trapezoidal rule. The MPA AUC(0-12) was higher for i.v. MMF than p.o. MMF (40.8 +/- 11.4 microg x h/ mL vs. 32.9 +/- 15, p < 0.001). There were no other significant PK differences for plasma MPA or MPAG. In the safety study (n = 98 i.v. MMF vs. n = 55 placebo), 11 patients (11%, i.v. MMF) and 4 patients (7%, placebo) discontinued their use of the drug because of an adverse event (AE). Overall, AEs were similar between i.v. MMF and placebo. Injection site phlebitis (4%) and thrombosis (4%) were observed only with i.v. MMF. MMF i.v. 1 g twice daily (b.i.d.) should provide efficacy at least equivalent to p.o. MMF without increased toxicity, and it provides an acceptable alternative dose form in the immediate period after transplant.

Administration, Oral↗

PubMed2000

Subcortical ischemic vascular dementia: assessment with quantitative MR imaging and 1H MR spectroscopy.

BACKGROUND AND PURPOSE: Subcortical ischemic vascular dementia is associated with cortical hypometabolism and hypoperfusion, and this reduced cortical metabolism or blood flow can be detected with functional imaging such as positron emission tomography. The aim of this study was to characterize, by means of MR imaging and 1H MR spectroscopy, the structural and metabolic brain changes that occur among patients with subcortical ischemic vascular dementia compared with those of elderly control volunteers and patients with Alzheimer's disease. METHODS: Patients with dementia and lacunes (n = 11), cognitive impairment and lacunes (n = 14), and dementia without lacunes (n = 18) and healthy age-matched control volunteers (n = 20) underwent MR imaging and 1H MR spectroscopy. 1H MR spectroscopy data were coanalyzed with coregistered segmented MR images to account for atrophy and tissue composition. RESULTS: Compared with healthy control volunteers, patients with dementia and lacunes had 11.74% lower N-acetylaspartate/creatine ratios (NAA/Cr) (P = .007) and 10.25% lower N-acetylaspartate measurements (NAA) in the cerebral cortex (P = .03). In white matter, patients with dementia and lacunes showed a 10.56% NAA/Cr reduction (P = .01) and a 12.64% NAA reduction (P = .04) compared with control subjects. NAA in the frontal cortex was negatively correlated with the volume of white matter signal hyperintensity among patients with cognitive impairment and lacunes (P = .002). Patients with dementia, but not patients with dementia and lacunes, showed a 10.33% NAA/Cr decrease (P = .02) in the hippocampus compared with healthy control volunteers. CONCLUSION: Patients with dementia and lacunes have reduced NAA and NAA/Cr in both cortical and white matter regions. Cortical changes may result from cortical ischemia/infarction, retrograde or trans-synaptic injury (or both) secondary to subcortical neuronal loss, or concurrent Alzheimer's pathologic abnormalities. Cortical derangement may contribute to dementia among patients with subcortical infarction.

Aged↗

PubMed1999

Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group.

BACKGROUND: Cytomegalovirus (CMV) disease is a major complication of organ transplantation. We hypothesized that prophylactic treatment with valacyclovir would reduce the risk of CMV disease. METHODS: A total of 208 CMV-negative recipients of a kidney from a seropositive donor and 408 CMV-positive recipients were randomly assigned to receive either 2 g of valacyclovir or placebo orally four times daily for 90 days after transplantation, with the dose adjusted according to renal function. The primary end point was laboratory-confirmed CMV disease in the first six months after transplantation. RESULTS: Treatment with valacyclovir reduced the incidence or delayed the onset of CMV disease in both the seronegative patients (P<0.001) and the seropositive patients (P=0.03). Among the seronegative patients, the incidence of CMV disease 90 days after transplantation was 45 percent among placebo recipients and 3 percent among valacyclovir recipients. Among the seropositive patients, the respective values were 6 percent and 0 percent. At six months, the incidence of CMV disease was 45 percent among seronegative recipients of placebo and 16 percent among seronegative recipients of valacyclovir; it was 6 percent among seropositive placebo recipients and 1 percent among seropositive valacyclovir recipients. At six months, the rate of biopsy-confirmed acute graft rejection in the seronegative group was 52 percent among placebo recipients and 26 percent among valacyclovir recipients (P=0.001). Treatment with valacyclovir also decreased the rates of CMV viremia and viruria, herpes simplex virus disease, and the use of inpatient medical resources. Hallucinations and confusion were more common with valacyclovir treatment, but these events were not severe or treatment-limiting. The rates of other adverse events were similar among the groups. CONCLUSIONS: Prophylactic treatment with valacyclovir is a safe and effective way to prevent CMV disease after renal transplantation.

Acyclovir↗

PubMed1999

Elevated subcortical choline metabolites in cognitively and clinically asymptomatic HIV+ patients.

OBJECTIVE: To determine whether the concentrations of the neuronal marker N-acetylaspartate (NAA) and the choline-containing metabolites (Cho) are altered in the subcortical brain of HIV+ patients who are cognitively normal and clinically asymptomatic, and to determine whether these alterations are greater in the presence of cognitive impairments and clinical symptoms. BACKGROUND: Pathologic studies suggest that subcortical gray matter carries a heavy HIV load, and neuropsychological test results are consistent with involvement of subcortical and frontostriatal brain systems in HIV disease. Noninvasive proton magnetic resonance spectroscopy (1H MRS) suggests neuronal preservation and macrophage infiltration in the subcortical brain of clinically symptomatic and cognitively impaired HIV+ individuals. Improved 1H MRS methods may allow the early detection of metabolite alterations in the subcortical brain of asymptomatic HIV+ individuals. METHODS: Two-dimensional 1H MRS imaging was performed on 30 HIV- control subjects and 70 HIV+ patients with varying severities of systemic disease and neuropsychological impairments, but without cerebral opportunistic infections. RESULTS: Subcortical Cho was elevated in HIV+ patients compared with control subjects regardless of the presence or absence of cognitive impairment or clinical symptoms. Subcortical NAA was lower than control NAA only in severely cognitively impaired HIV+ subjects. Subcortical NAA correlated with performance on a variety of neuropsychological tests but not with Centers for Disease Control clinical stage, whereas high-thalamic Cho was associated with low CD4 lymphocyte counts. CONCLUSIONS: 1H MRS imaging detects higher Cho in subcortical brain early in HIV disease, when individuals are clinically and neuropsychologically asymptomatic, whereas lower NAA is only found in subcortical brain in individuals with severe neuropsychological impairments. Quantitative 1H MRS imaging may play a role in the objective assessment of the presence, magnitude, and progression of brain involvement in HIV infection.

Adult↗

PubMed1999

Effects of subcortical cerebral infarction on cortical glucose metabolism and cognitive function.

BACKGROUND: The mechanism of dementia in subcortical cerebral infarction is incompletely understood. OBJECTIVE: To determine how cognitive function is related to cortical metabolism in patients with subcortical infarction and a continuum of cognitive impairment. METHODS: We used positron emission tomography (PET) and the glucose metabolic tracer fludeoxyglucose F 18 to study 8 patients with subcortical stroke and normal cognitive function (S-CN), 5 patients with subcortical stroke and cognitive impairment (S-CI) who did not have dementia, 8 patients with subcortical stroke and dementia (S-D), and 11 controls with no cognitive impairment or stroke. A subset of patients had absolute regional cerebral metabolic rate of glucose (CMRglc) determined, while in all subjects regional tracer uptake normalized to whole brain tracer uptake was calculated. PET data were analyzed by constructing volumes of interest using coregistered magnetic resonance imaging data and correcting the PET data for atrophy. RESULTS: Global CMRglc was significantly lower in the patients with S-D than in the control and S-CN groups, with S-CI rates intermediate to those of the S-D and S-CN groups. Absolute regional CMRs of glucose were similar in the S-D and S-CI groups and in the control and S-CN groups. The regional pattern, however, showed lower right frontal regional CMRglc ratios in all stroke groups compared with the controls. There were modest correlations between performance on the Mini-Mental State Examination and whole brain CMRglc when all 4 groups were included. CONCLUSIONS: These results demonstrate that subcortical infarction produces global cerebral hypometabolism, which is related to the clinical status of the patients. In addition, specific frontal lobe hypometabolism also appears to be a feature of subcortical infarction. Taken together, both global and regional effects on cortical function mediate the production of clinical symptoms in patients with subcortical strokes.

Aged↗

PubMed1999

Treatment of experimental avascular necrosis of the femoral head with hyperbaric oxygen in rats: histological evaluation of the femoral heads during the early phase of the reparative process.

The healing of vascular deprivation-induced necrosis of the femoral head of rats exposed to hyperbaric oxygen was compared with that in untreated rats. The amount of necrotic bone, extent of osteoneogenesis, degree of remodeling, and changes of the articular cartilage were histologically graded on a semiquantitative scale of 0 to 3+. On the 2nd, 7th, and 21st postoperative days, there were no differences between the two groups. Newly formed appositional and intramembranous bone was more abundant and remodeling was more advanced in the femoral heads of the hyperbaric oxygen-treated than untreated rats sacrificed on the 42nd postoperative day; also there was less necrotic debris in the femoral heads of the treated rats. There were no differences in the severity of the degenerative changes of the articular cartilage of the treated and untreated rats. Exposure of rats to hyperbaric oxygen does not preserve tissue viability after all arteries supplying the femoral head are severed. Yet, resulting in an increased oxygen tension of the tissues, it seems to provide the optimal settings for reparative processes. The results suggest that hyperoxygenation-mediated relief of ischemia enhances the fibroblastic, angioblastic, osteoblastic, and osteoclastic activities such that healing of the rats' necrotic femoral heads is expedited.

Animals↗

PubMed1999

Osteoarthritis-like disorder in rats with vascular deprivation-induced necrosis of the femoral head.

The reparative processes following vascular deprivation-induced necrosis of the femoral head were studied histologically in rats sacrificed 2, 7, 14, 21, 42 and 92 days postoperatively. The blood supply was severed by incision of the periosteum at the neck of the femoral head and transection of the ligamentum teres. Granulation tissue and a well-vascularized fibrous tissue originating from the joint capsule invaded the necrotic marrow spaces. With progressive resorption of the necrotic tissues and osteoneogenesis, both appositional and intramembranous, within the fibrotic intertrabecular spaces, the remodeling process led to a shift of the normal spongy architecture of the femoral head to a compacta-like one. In a few cases, osseous bridges bisected a necrotic physeal cartilage at the latest time intervals. The remodeling was associated with flattening of the femoral heads as well as with degenerative, regenerative and reparative alterations of the articular cartilage. In one of the two femoral heads obtained three months postoperatively, cystic spaces developed in the fibrous subchondral zone. Our findings are consistent with the view that ineffective attempts at restoring the prenecrotic state of the femoral head by replacing the necrotic with viable tissue triggers the collapse of the femoral head. Thickening and condensation of the subchondral bone, leading to increased stiffness of the subchondral zone, result in the osteoarthritis-like disorder. Mimicking the well-known phases of human osteonecrosis, the model readily allows for preclinical studies of therapeutic regimens.

Animals↗

PubMed1999

Characterization of a novel cellular defect in patients with phenotypic homozygous familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is characterized by a raised concentration of LDL in plasma that results in a significantly increased risk of premature atherosclerosis. In FH, impaired removal of LDL from the circulation results from inherited mutations in the LDL receptor gene or, more rarely, in the gene for apo B, the ligand for the LDL receptor. We have identified two unrelated clinically homozygous FH patients whose cells exhibit no measurable degradation of LDL in culture. Extensive analysis of DNA and mRNA revealed no defect in the LDL receptor, and alleles of the LDL receptor or apo B genes do not cosegregate with hypercholesterolemia in these families. FACS((R)) analysis of binding and uptake of fluorescent LDL or anti-LDL receptor antibodies showed that LDL receptors are on the cell surface and bind LDL normally, but fail to be internalized, suggesting that some component of endocytosis through clathrin-coated pits is defective. Internalization of the transferrin receptor occurs normally, suggesting that the defective gene product may interact specifically with the LDL receptor internalization signal. Identification of the defective gene will aid genetic diagnosis of other hypercholesterolemic patients and elucidate the mechanism by which LDL receptors are internalized.

Adolescent↗

PubMed1999

Magnetization transfer ratio of white matter hyperintensities in subcortical ischemic vascular dementia.

BACKGROUND AND PURPOSE: In subjects with subcortical ischemic vascular dementia (SIVD), tissue vacuolization, myelin pallor, and demyelination have been found on pathologic examination of white matter signal hyperintensities (WMSH). Magnetization transfer ratio (MTR) values provide a potential measure of compromised white matter integrity. The purpose of this study was to determine if there were differences in MTR of WMSH between subjects with SIVD and cognitively normal healthy control subjects. METHODS: Fifteen subjects with SIVD and 16 control subjects of comparable age and sex were studied. MTR images were coregistered to MR images segmented into tissue classes (gray matter, white matter, CSF, WMSH, and lacunar infarcts). MTR of WMSH was compared across groups and examined by WMSH location, size, and total burden. RESULTS: WMSH burden was greater in SIVD patients than in control subjects (2.4% vs 0.67%). MTR of WMSH did not differ between groups, but MTR of periventricular WMSH was lower in SIVD patients than in control subjects (37.6% vs 39.4%). Even after accounting for covariant effects of lesion burden, there was still a trend toward reduced periventricular WMSH MTR in the group with dementia. There was no correlation between WMSH MTR and WMSH lesion size. CONCLUSION: These findings are consistent with observations that pathologic changes in vascular dementia are most severe in the periventricular white matter and suggest that insight into the pathophysiology of SIVD might be gleaned from studies of the periventricular region.

Aged↗

PubMed1998

The effect of tolerance to noninherited maternal HLA antigens on the survival of renal transplants from sibling donors.

BACKGROUND: During pregnancy and nursing, a baby's developing immune system is intimately exposed to the mother's antigens. To determine whether this exposure is of clinical benefit to patients who later receive an allograft as an adult, we analyzed the outcome of primary renal transplantations from sibling donors. METHODS: We retrospectively studied graft survival and rejection episodes in 205 patients who had received renal transplants at nine centers between 1966 and 1996 from sibling donors bearing maternal or paternal HLA antigens not inherited by the recipient. The sibling donors were categorized by analysis of family HLA-typing data. RESULTS: In the multicenter analysis, graft survival was higher at 5 years and at 10 years after transplantation in recipients of kidneys from siblings expressing maternal HLA antigens not inherited by the recipient than in recipients of kidneys from siblings expressing paternal HLA antigens not inherited by the recipient (86 percent vs. 67 percent at 5 years and 77 percent vs. 49 percent at 10 years, P=0.006 for both). Paradoxically, there was a higher incidence of early rejection in the former group, suggesting that fetal and neonatal exposure to maternal antigens results in immunologic priming. Pretransplantation transfusions of donor blood reduced the incidence of acute rejection while preserving the beneficial effect of tolerance to noninherited maternal antigens on graft survival. Since 1986, new immunosuppressive drugs have lessened the short-term, but not the long-term, survival advantage of grafts expressing maternal HLA antigens not inherited by the recipient. CONCLUSIONS: In the transplantation of a kidney from a sibling donor who is mismatched with the recipient for one HLA haplotype, graft survival is higher when the donor has maternal HLA antigens not inherited by the recipient than when the donor has paternal HLA antigens not inherited by the recipient.

Fathers↗

PubMed1998

Demonstration of a tandem pair of complement protein modules in GABA(B) receptor 1a.

We have subcloned and expressed the N-terminal portion of the recently sequenced metabotropic GABA receptor, GABA(B)R1a. This region of the receptor contains a complement protein-like amino acid sequence. The purified 140-residue recombinant protein fragment was soluble and stable. Mass spectrometry indicated formation of four disulfide bonds, as expected if two complement protein modules (CPs, also known as SCRs, Sushi domains) are formed. The circular dichroism spectrum was unusual and characteristic of CPs. Differential scanning calorimetry demonstrated a melting point (64 degrees C), and total enthalpy commensurate with two fully folded domains. We thus conclude that the 1a subtype of the GABA(B) receptor, but not the 1b subtype, contains a pair of CPs and we present a three-dimensional model of this region.

Amino Acid Sequence↗

PubMed1998

The importance of combined clinical and sonographic examination of instability of the neonatal hip.

A clinically unstable hip in a new-born may be an early sign of congenital dysplasia. Unless followed and treated at a young age, it can progress to a degenerative hip joint disorder with considerable functional disability in adult life. For this reason, the early diagnosis of neonatal hip instability is crucial. We present our experience with 9199 neonates examined independently by clinical and ultrasonographic techniques. Instability was diagnosed in 0.8% of the hips. Only 47% of the unstable hips were diagnosed by the initial clinical examination, in the remainder the dysplasia was recognised only by sonography. Sonographic changes were also detected on re-examination in 6% of the unstable hips following the recognition of clinical instability. It is evident that combined clinical and ultrasonographic examination significantly improves the detection rate of dysplastic hips in new-borns.

Female↗

PubMed1998

Premorbid brain size is a determinant of functional reserve in abstinent crack-cocaine and crack-cocaine-alcohol-dependent adults.

Studies of Alzheimer's disease patients show that individuals with larger premorbid brains have a later onset of disease, or a lessened severity of cognitive impairment, or both. This may be due to a "functional reserve" associated with the greater number of neurons and synapses available in larger brains. We used magnetic resonance imaging and the MicroCog Assessment of Cognitive Functioning to examine the association between intracranial volume (premorbid brain size) and neuropsychological function in abstinent crack-cocaine and crack-cocaine-alcohol dependent individuals. There were no significant differences between the crack-only and the crack-alcohol dependent participants in neuropsychological performance or in intracranial volume. The abstinent cocaine-dependent individuals (both crack-only and crack-alcohol) were significantly impaired in many neuropsychological domains. Intracranial volume accounted for a significant proportion of the variance in neuropsychological performance. This result is consistent with the finding in the Alzheimer's literature that larger brains can maintain function to a greater degree, or for a longer period of time, in the face of cerebral disease or insult. Functional reserve may be a heretofore little recognized protective mechanism of the brain that has consequences for the severity of expression of cerebral disease or insult throughout life.

Adult↗