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Biomedical subjects

D Norman

Publications and source records attributed to D Norman.

At least 109 records · Page 6Linked to original sources
PubMed1991

Long-term metabolic and quality of life results with pancreatic/renal transplantation in insulin-dependent diabetes mellitus.

Evaluation of whole-organ pancreas transplantation in the therapy of IDDM has been difficult because of generally poor graft survival and significant complications in past experience. We report a technically successful simultaneous pancreas/kidney transplant program with patient and graft survival of 85% over 3 years of follow-up (mean 21 months) in 33 subjects with IDDM. Glucose metabolism was normalized without need for exogenous insulin immediately posttransplant in all but one recipient and remained normal in 85% of recipients. The outcome in pancreas/kidney recipients was compared with that in 18 insulin-dependent diabetic recipients of kidney transplant only performed in the same period. Quality of life was assessed with one general and one diabetes-specific questionnaire. General quality of life issues improved significantly in both pancreas/kidney and kidney recipients, but diabetes specific quality of life improved only in the pancreas/kidney recipients. Pancreas/kidney recipients required twice as long a period of hospitalization for the transplant and two times as many readmissions for a variety of complications. Only a minority of hospital admissions was strictly attributable to the pancreas graft. Of the five deaths in the pancreas/kidney recipients, two were attributable to the pancreas transplant. Pancreas transplantation in IDDM can now be accomplished with a high degree of success, resulting in normalized glucose metabolism and with overall mortality similar to kidney transplantation alone. Successful pancreas transplantation improves quality of life with respect to diabetes but this benefit is accomplished at a cost of increased hospital admissions and complications related to the transplanted pancreas. The effects of pancreas transplantation on the long-term complications of insulin-dependent diabetes remain unknown.

Adult↗
PubMed1991

Plasma tumour necrosis factor alpha in cystic fibrosis.

Plasma tumour necrosis factor alpha (alpha) concentration is increased in acute Gram negative sepsis, but the effect of chronic infection on plasma concentrations is unknown. A study was carried out in patients with cystic fibrosis to determine the effect of chronic lung infection with Pseudomonas aeruginosa on the plasma concentration of tumour necrosis factor and two other indicators of the inflammatory response, circulating C reactive protein and neutrophil elastase-alpha 1 antiproteinase complex (elastase complex). The concentration of immunoreactive tumour necrosis factor in plasma was greater than the upper 95% confidence interval for healthy subjects (2.6 U/ml) on 129 out of 189 occasions in 14 patients observed for about a year. The increase in tumour necrosis factor was associated with increased circulating C reactive protein and elastase complex. Twelve patients with an exacerbation of respiratory symptoms were studied before and after two weeks' treatment with anti-pseudomonal antibiotics. All three indicators of the inflammatory response fell after treatment, though median tumour necrosis factor (4.8 U/ml) and elastase complex (0.41 microgram/ml) concentrations remained above the upper limits for healthy subjects. During a period of clinical stability plasma tumour necrosis factor was increased in 10 of the 12 patients, elastase complex was increased in 10 of the 12, and C reactive protein was increased in seven. Increased plasma immunoreactive tumour necrosis factor was a feature of the near continuous inflammatory response to chronic P aeruginosa infection in cystic fibrosis and may be a factor contributing to the progressive lung destruction seen in this disease.

Adolescent↗
PubMed1991

Ischemic brain damage: reduction by sodium-calcium ion channel modulator RS-87476.

A novel sodium-calcium ion channel modulator, RS-87476, reduced cerebral infarct size in cats subjected to permanent unilateral occlusion of the middle cerebral artery. Cerebral injury was assessed in vivo with a combination of magnetic resonance (MR) imaging and spectroscopy for 5-12 hours after occlusion and was compared with the area of histochemically ischemic brain tissue. Compared with infarcts in placebo-treated animals, infarcts in cats given RS-87476 were reduced by an average of 70% at the lowest dose, 75% at the intermediate dose, and 88% at the highest dose. Tissue edema, observed as areas of signal hyperintensity on diffusion- and T2-weighted spin-echo images, was confined to small regions of the parietal cortex and basal ganglia in drug-treated animals. Mean plasma levels of RS-87476 at the lowest dose were 13 ng/mL initially, falling to maintenance levels of 3-5 ng/mL; at the intermediate and highest doses, plasma levels of drug were approximately five- and 20-fold greater. The drug was only slightly hypotensive. At least part of the potent cerebroprotective effects of RS-87476 result from its ability to stabilize metabolic energy reserves, reduce lactate formation in ischemic tissues, and attenuate intracerebral edema.

Animals↗
PubMed1991

HLA-A2, or a closely linked gene, confers susceptibility to early-onset sporadic Alzheimer's disease in men.

There is a weak association between Alzheimer's disease (AD) and the histocompatibility antigen HLA-A2, suggesting that A2 has either a minor role in AD or a major role in a subtype of it. To test these alternatives, we studied 54 consecutively ascertained AD patients diagnosed by NINCDS-ADRDA criteria. Patients had a higher frequency of A2 than control subjects, primarily due to the elevated frequency of this antigen in men with early onset of dementia (less than or equal to 60 years): 92% of early-onset men had A2 as compared with 44% of controls. This finding suggests that A2, or a closely linked gene, confers susceptibility to early-onset AD in men. Furthermore, A2 appears to be primarily associated with sporadic AD, rather than with the familial subtype.

Age Factors↗
PubMed1991

Cerebrovascular disease.

The recent literature addresses the early detection of cerebrovascular disease using imaging techniques, metabolic assessment using spectroscopy, developments in quantitative analysis of brain blood flow, and new interventional techniques for aneurysm obliteration and carotid angioplasty.

Cerebral Angiography↗
PubMed1990

Structure of the fibronectin type 1 module.

The rapid accumulation of sequence data has provided insight into the evolution of proteins and led to the identification of 'mosaic proteins'. These proteins have evolved by duplication, insertion and deletion of a common pool of structural units or modules, yet their biological functions are diverse. They are involved in cell adhesion and migration, embryogenesis and the pathways of blood clotting, fibrinolysis and complement. The modular units are defined by 'consensus sequences' which often include conserved disulphide bonds. Despite the available sequence information, little is known of the tertiary structure of mosaic proteins. If, however, the 'consensus structure' of the modules were known, valuable structural information could be inferred about a wide variety of proteins and biological systems. An important mosaic protein is fibronectin, an extracellular matrix protein that consists of three types of module (see refs 3, 7 for reviews). Here we describe the structure of the fibronectin type 1 module which appears twelve times in fibronectin and is also found in factor XII and tissue plasminogen activator. The module was produced using a yeast expression system and the structure was determined in solution using 1H NMR. This methodology promises to be extremely powerful in the investigation of modules from a wide range of mosaic proteins.

Amino Acid Sequence↗
PubMed1990

NMR and computational characterization of mitomycin cross-linked to adjacent deoxyguanosines in the minor groove of the d(T-A-C-G-T-A).d(T-A-C-G-T-A) duplex.

Two-dimensional homonuclear and heteronuclear NMR and minimized potential energy calculations have been combined to define the structure of the antitumor agent mitomycin C (MC) cross-linked to deoxyguanosines on adjacent base pairs in the d(T1-A2-C3-G4-T5-A6).d(T7-A8-C9-G10-T11-A12) duplex. The majority of the mitomycin and nucleic acid protons in the MC-X 6-mer complex have been assigned from through-bond and through-space two-dimensional proton NMR studies in aqueous solution at 5 and 20 degrees C. The C3.G10 and G4.C9 base pairs are intact at the cross-link site and stack on each other in the complex. The amino protons of G4 and G10 resonate at 9.36 and 8.87 ppm and exhibit slow exchange with solvent H2O. The NMR experimental data establish that the mitomycin is cross-linked to the DNA through the amino groups of G4 and G10 and is positioned in the minor groove. The conformation of the cross-link site is defined by a set of NOEs between the mitomycin H1" and H2" protons and the nucleic acid imino and amino protons of G4 and the H2 proton of A8 and another set of NOEs between the mitomycin geminal H10" protons and the nucleic acid imino and amino protons of G10 and the H2 proton of A2. Several phosphorus resonances of the d(T-A-C-G-T-A) duplex shift dramatically on mitomycin cross-link formation and have been assigned from proton-detected phosphorus-proton two-dimensional correlation experiments. The proton chemical shifts and NOEs establish fraying at the ends of the d(T-A-C-G-T-A) duplex, and this feature is retained on mitomycin cross-link formation. The base-base and base-sugar NOEs exhibit similar patterns for symmetry-related steps on the two nucleic acid strands in the MC-X 6-mer complex, while the proton and phosphorus chemical shifts are dramatically perturbed at the G10-T11 step on cross-link formation. The NMR distance constraints have been included in minimized potential energy computations on the MC-X 6-mer complex. These computations were undertaken with the nonplanar five-membered ring of mitomycin in each of two pucker orientations. The resulting low-energy structures MX1 and MX2 have the mitomycin cross-linked in a widened minor groove with the chromophore ring system in the vicinity of the G10-T11 step on one of the two strands in the duplex.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗
PubMed1990

Early detection of ischemic injury: comparison of spectroscopy, diffusion-, T2-, and magnetic susceptibility-weighted MRI in cats.

Within one hour following MCA-occlusion in cats, heavily diffusion-weighted spin-echo MR images exhibited a well-defined hyperintensity in the gray matter and basal ganglia of the occluded side over normal side. This hyperintensity correlated with lactate and inorganic phosphate increases in peak areas from MR surface coil spectroscopy. T2-weighted MRI showed no significant abnormality in signal intensity from the occluded hemisphere within several hours post-occlusion. Using a paramagnetic MR contrast agent, dysprosium-DTPA-BMA together with heavily T2-weighted spin-echo or with T2*-weighted echo-planar (EPI) MR imaging, perfusion deficits resulting from MCA-occlusion were detected as a relative hyperintensity of ischaemic tissues compared to normally-perfused cerebral tissues in the contralateral hemisphere. Evidence of these deficits was observed within minutes of occlusion, and spatially correlated well with the hyperintensity seen on the diffusion-weighted images. Diffusion- and susceptibility-weighted MRI was superior to conventional T2-weighted MRI in the detection of early ischaemic events. In contrast to surface coil spectroscopy, both techniques mapped regions of jeopardy throughout the brain, which later showed T2-weighted hyperintensity and lack of vital (TTC) staining.

Animals↗
PubMed1990

Diffusion-weighted MR imaging and T2-weighted MR imaging in acute cerebral ischaemia: comparison and correlation with histopathology.

Diffusion-weighted MR imaging is a new technique which measures the microscopic motion of water protons. Signal hyperintensity on diffusion-weighted images correlates closely with evidence of ischaemic damage on histopathologic sections. Following occlusion of the middle cerebral artery (MCA), diffusion-weighted images indicate the presence of early pathophysiologic changes occurring first in the basal ganglia and, subsequently, in cortical gray matter within the MCA vascular territory. Diffusion-weighted images also better define the anatomic locus of ischaemic tissue injury than T2-weighted images. Diffusion-weighted imaging thus appears to facilitate early detection and thereby possible therapeutic intervention in patients with acute stroke.

Acute Disease↗
PubMed1990

An outbreak of an influenza-like illness in a nursing home.

As part of an ongoing infection surveillance program, data were collected on an outbreak of respiratory illness affecting 29% of residents in a 231-bed long-term care facility. Viral titers could be collected on 60% of the ill residents and respiratory syncytial virus (RSV) was established in 14 of the symptomatic patients and was thought to be the probable cause of the outbreak. Compared with previously reported long-term institutional outbreaks of RSV, there were significantly fewer cases of pneumonia (5% vs. 14% to 55%) and deaths (2% vs. 6% to 20%). However, morbidity was substantial in this outbreak, with 46% of patients suffering prolonged malaise and anorexia; the mean duration of symptoms was four weeks. Respiratory syncytial virus may be an important cause of respiratory illness in nursing homes and may be unappreciated if specific diagnostic methods are not employed. The recent availability of rapid diagnostic tests and specific antiviral therapy for RSV warrant further clinical studies to develop management strategies for this infection.

Aged↗
PubMed1990

Diffusion-weighted MR imaging of anisotropic water diffusion in cat central nervous system.

The diffusion behavior of intracranial water in the cat brain and spine was examined with the use of diffusion-weighted magnetic resonance (MR) imaging, in which the direction of the diffusion-sensitizing gradient was varied between the x, y, and z axes of the magnet. At very high diffusion-sensitizing gradient strengths, no clear evidence of anisotropic water diffusion was found in either cortical or subcortical (basal ganglia) gray matter. Signal intensities clearly dependent on orientation were observed in the cortical and deep white matter of the brain and in the white matter of the spinal cord. Greater signal attenuation (faster diffusion) was observed when the relative orientation of white matter tracts to the diffusion-sensitizing gradient was parallel as compared to that obtained with a perpendicular alignment. These effects were seen on both premortem and immediate postmortem images obtained in all axial, sagittal, and coronal views. Potential applications of this MR imaging technique included the stereospecific evaluation of white matter in the brain and spinal cord and in the characterization of demyelinating and dysmyelinating diseases.

Animals↗
PubMed1990

Loss of the insular ribbon: another early CT sign of acute middle cerebral artery infarction.

Although computed tomography (CT) remains the most frequently used imaging examination in acute cerebral infarction, its sensitivity for early detection of strokes remains limited. In middle cerebral artery (MCA) strokes less than 6 hours old, loss of definition of the gray-white interface in the lateral margins of the insula ("insular ribbon") was observed. The acute and subacute CT findings in 11 retrospective and 16 prospective patients are presented. Loss of the insular ribbon was detected in 12 of the prospective cases and in all 11 retrospective cases. The insular ribbon is supplied by the insular segment of the MCA and its claustral branches. With cessation of MCA flow, the insular ribbon becomes the region most distal from the anterior and posterior cerebral collateral circulations. Consequently, the insular ribbon effectively becomes a watershed arterial zone. Loss of the insular ribbon is thus a reflection of acute edema due to infarction. Loss of the insular ribbon appears to be another frequent and reliable finding in acute MCA stroke.

Aged↗
PubMed1990

Three-dimensional gradient-recalled MR imaging as a screening tool for the diagnosis of cervical radiculopathy.

The purpose of the study was to implement and assess a fast-screening, three-dimensional Fourier transformation (3DFT) MR sequence for the cervical spine. This sequence maintains adequate signal-to-noise and image contrast similar to gradient-recalled echo two-dimensional Fourier transformation (2DFT) imaging. Thirty patients with radiculopathy were examined with 3DFT gradient-recalled echo imaging. The data set consisted of 60 contiguous 1.5- to 2.0-mm-thick axial slices with a total coverage of 9 to 12 cm. In 10 patients, comparison was made with 4-mm-thick axial T1-weighted spin-echo 2DFT or gradient-recalled echo 2DFT studies. With the use of a volume acquisition, adequate signal-to-noise and image contrast similar to T2-weighted gradient-recalled echo 2DFT acquisitions were obtainable. Coverage was improved despite the use of thinner sections without interslice gap. Thin-section 3DFT provided superior detail of acquired foraminal and spinal canal stenosis and disk morphology. Limitations included increased sensitivity to patient motion and "wraparound" artifact in the slice-select direction. Overall, diagnostic confidence was improved with 3DFT owing to the reduction of partial volume artifact. We have adopted this technique as the primary screening method for diagnosing cervical radiculopathy.

Cervical Vertebrae↗
PubMed1990

Diffusion-weighted MR imaging of the brain: value of differentiating between extraaxial cysts and epidermoid tumors.

This study demonstrates the use of diffusion-weighted MR imaging in improving the specificity of the diagnosis of extraaxial brain tumors. Three surgically proved lesions (one arachnoid cyst and two epidermoid tumors) and two nonsurgically proved lesions (arachnoid and ependymal cysts) were evaluated with T1- and T2-weighted spin-echo studies followed by intravoxel incoherent motion (IVIM) MR imaging. The IVIM images of the lesions were displayed as an apparent diffusion coefficient (ADC) image obtained at 0.65 G/cm (maximum gradient b value = 100 sec/mm2) and compared with external oil and water phantoms. The ADC of arachnoid cysts was similar to stationary water whereas the ADC of epidermoid tumors was similar to brain parenchyma, indicating the solid nature and the slower diffusion rate of the epidermoid tumors. Cisternal CSF demonstrated uniformly high ADC, primarily because of bulk flow, which enhanced image contrast. Improved delineation of postsurgical changes was also possible. Our preliminary results show that diffusion-weighted MR imaging can be useful in distinguishing between arachnoid cysts and epidermoid tumors.

Adult↗
PubMed1990

Diffusion-weighted MR imaging of acute stroke: correlation with T2-weighted and magnetic susceptibility-enhanced MR imaging in cats.

We evaluated the temporal and anatomic relationships between changes in diffusion-weighted MR image signal intensity, induced by unilateral occlusion of the middle cerebral artery in cats, and tissue perfusion deficits observed in the same animals on T2-weighted MR images after administration of a nonionic intravascular T2 shortening agent. Diffusion-weighted images obtained with strong diffusion-sensitizing gradient strengths (5.6 gauss/cm, corresponding to gradient attenuation factor, b, values of 1413 sec/mm2) displayed increased signal intensity in the ischemic middle cerebral artery territory less than 1 hr after occlusion, whereas T2-weighted images without contrast usually failed to detect injury for 2-3 hr after stroke. After contrast administration (0.5-1.0 mmol/kg by Dy-DTPA-BMA, IV), however, T2-weighted images revealed perfusion deficits (relative hyperintensity) within 1 hr after middle cerebral artery occlusion that corresponded closely to the anatomic regions of ischemic injury shown on diffusion-weighted MR images. Close correlations were also found between early increases in diffusion-weighted MR image signal intensity and disrupted phosphorus-31 and proton metabolite levels evaluated with surface coil MR spectroscopy, as well as with postmortem histopathology. These data indicate that diffusion-weighted MR images more accurately reflect early-onset pathophysiologic changes induced by acute cerebral ischemia than do T2-weighted spin-echo images.

Acute Disease↗