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Biomedical subjects

C A Clark

Publications and source records attributed to C A Clark.

At least 55 records · Page 3Linked to original sources

Wallerian degeneration in the optic radiation after temporal lobectomy demonstrated in vivo with diffusion tensor imaging.

PURPOSE: Diffusion tensor imaging allows the quantitative assessment of the microstructural organization of tracts in vivo (MR tractography). We used the new technique of MR tractography to demonstrate the effects of temporal lobectomy on the optic radiation. METHODS: Spatially normalised maps encoding magnitude of the bias (anisotropy) of diffusion of three patients with temporal lobe resections were compared with spatially normalised diffusion maps of 22 control subjects. All three patients were operated on for the treatment of medically intractable temporal lobe epilepsy and had a normal neurologic examination before surgery. One patient had an amygdalocorticectomy. Two patients had standard en bloc resections, one of whom developed a homonymous hemianopia after surgery. RESULTS: In the patient with hemianopia, a significant reduction of diffusion anisotropy (greater than mean+/-2 SD) consistent with wallerian degeneration was demonstrated in the optic radiation on the side of the temporal lobectomy, extending from the temporal to the occipital lobe. In the other patient with standard en bloc resection but clinically no hemianopia, the optic radiation was only marginally affected. In the third patient (amygdalocorticectomy), the diffusion anisotropy was within the normal range in the expected position of the optic radiation. CONCLUSIONS: Our findings show that MR tractography may be a useful tool to demonstrate wallerian degeneration in the optic radiation after temporal lobectomy in patients with hemianopia. This is the first time that this new method has been applied in postoperative imaging; it enables us to visualise the morphologic correlate of dysfunctional pathways after epilepsy surgery in vivo. The potential for using MR tractography to study other aspects of epilepsy is discussed.

Anisotropy↗

Clinical severity in CADASIL related to ultrastructural damage in white matter: in vivo study with diffusion tensor MRI.

BACKGROUND AND PURPOSE: CADASIL is a newly recognized cause of subcortical ischemic strokes that progressively leads to dementia associated with pseudobulbar palsy and severe motor disability. This deleterious progression and the severity of clinical presentation are widely variable among affected subjects. The exact role played by MRI white-matter abnormalities, a hallmark of the disease, in the severity of the clinical phenotype remains poorly understood. METHODS: To address this issue, we used diffusion tensor imaging (DTI), a new MRI technique highly sensitive to white-matter microstructural changes, in 16 symptomatic patients and 10 age-matched controls. Mean diffusivity and anisotropy of diffusion were measured within hyperintensities identified on T2-weighted images (T2WI) and outside these lesions on 4 slices at the level of centrum semiovale. RESULTS: We found a 60% increase of water mean diffusivity and a parallel loss of diffusion anisotropy in hyperintensities identified on T2WI. The same pattern of diffusion changes, but of lesser intensity, was found in the normal-appearing white matter on T2WI. Mean diffusivity in regions with increased signal on T2WI was higher in patients with severe clinical disability compared with those with no or mild deficit (1.33+/-0.11 versus 1.13+/-0.11 10(-3) mm(2)/s, P<0.01). Furthermore, diffusion measured within T2 hyperintensities correlated with both the Mini-Mental State Examination and Rankin scale scores. In patients with a severe clinical status, the increase of water diffusion in these regions exceeded 70% in comparison with values obtained in the normal white matter in control subjects. CONCLUSIONS: These results indicate that DTI is able to detect important ultrastructural changes in regions with increased signal on T2WI and within the normal-appearing white matter in CADASIL. The diffusion changes might be related to both neuronal loss and demyelination. The degree of the underlying ultrastructural alterations is related to the severity of the clinical status with a possible threshold level of white-matter damage above which severe neurological impairment may occur in this disease. DTI appears to be a promising technique for monitoring disease progression in CADASIL.

Adult↗

The structural and functional mechanisms of motor recovery: complementary use of diffusion tensor and functional magnetic resonance imaging in a traumatic injury of the internal capsule.

OBJECTIVES: Recovery from focal motor pathway lesions may be associated with a functional reorganisation of cortical motor areas. Previous studies of the relation between structural brain damage and the functional consequences have employed MRI and CT, which provide limited structural information. The recent development of diffusion tensor imaging (DTI) now provides quantitative measures of fibre tract integrity and orientation. The objective was to use DTI and functional MRI (fMRI) to determine the mechanisms underlying the excellent recovery found after a penetrating injury to the right capsular region. METHODS: DTI and fMRI were performed on the patient described; DTI was performed on five normal controls. RESULTS: The injury resulted in a left hemiplegia which resolved fully over several weeks. When studied 18 months later there was no pyramidal weakness, a mild hemidystonia, and sensory disturbance. fMRI activation maps showed contralateral primary and supplementary motor cortex activation during tapping of each hand; smaller ipsilateral primary motor areas were activated by the recovered hand only. DTI disclosed preserved structural integrity and orientation in the posterior capsular limb by contrast with the disrupted structure in the anterior limb on the injured side. CONCLUSIONS: The findings suggest that the main recovery mechanism was a preservation of the integrity and orientation of pyramidal tract fibres. The fMRI studies do not suggest substantial reorganisation of the motor cortex, although ipsilateral pathways may have contributed to the recovery. The initial deficit was probably due to reversible local factors including oedema and mass effect; permanent damage to fibre tracts in the anterior capsular limb may account for the persistent sensory deficit. This study shows for the first time the potential value of combining fMRI and DTI together to investigate mechanisms of recovery and persistent deficit in an individual patient.

Adult↗

Consumer satisfaction with nursing care in a rural community hospital emergency department.

The article describes a study undertaken to assess patient satisfaction with nursing care in a rural hospital emergency department with respect to psychological safety, discharge teaching, information giving, and technical competence. This descriptive research utilized Davis' Consumer Emergency Care Satisfaction Scale to determine the degree to which 52 patients perceived overall satisfaction with nursing care. Findings indicated that patients were satisfied with nursing care. No statistically significant effect of gender or education level on consumer satisfaction or on any subscale was detected, but African American consumers were less satisfied with discharge teaching, which may suggest that discharge teaching should reflect the cultural diversity of consumers presenting to the emergency department. Nursing staff may need to spend more time with rural African American consumers. Staff may need to be inserviced to meet the cultural and educational needs of African Americans.

Adult↗

The dietary adequacy of edentulous older adults.

This study tested the null hypothesis that there are no differences in dietary patterns or adequacy between edentulous patients and individuals with nearly complete dentitions. The research design involved comparing the dietary patterns and adequacies of 34 edentulous subjects who regularly wear dentures with 38 subjects who had nearly complete dentitions. The subjects were between the ages of 51 and 83 years and were sampled from patients attending Case Western Reserve University Dental Clinic. Although edentulous subjects were more likely to claim that they had trouble chewing their food, they were not more likely to select easy-to-chew foods. On the other hand, the diet of dentate subjects tended to be superior to that of edentulous subjects, as indicated by a lower fat and cholesterol consumption and a higher consumption of protein and all of the vitamins and minerals (significantly or nearly significantly for vitamin A, ascorbic acid, calcium, and riboflavin).

Aged↗

Identification of VCR, a repeated sequence associated with a locus encoding a hemagglutinin in Vibrio cholerae O1.

We have determined the nucleotide sequence of a 6.3-kb BamHI fragment of the chromosome of Vibrio cholerae 569B that includes the sequence of the mannose-fucose-resistant hemagglutinin reported previously (V.L. Franzon, A. Barker, and P. A. Manning, Infect. Immun. 61:3032-3037, 1993). This region contains nine copies of a 124-bp direct repeat, here named VCR, of imperfect dyad symmetry, that are shown by Southern hybridization to occur at least 60 to 100 times in the V. cholerae O1 chromosome. Large-scale chromosomal mapping suggests that the repeats are confined to about 10% of the chromosome. Related sequences are also found in non-O1 V. cholerae but not in other members of the family Vibrionaceae. However, VCR is unrelated to other previously described repetitive sequences.

Amino Acid Sequence↗

Elevated glucose alters A23187-induced release of arachidonic acid from porcine aortic endothelial cells by enhancing reacylation.

Cultured porcine aortic endothelial cells were conditioned in normal (5.2 mM) and elevated (15.6 mM) glucose, prelabeled with [14C]arachidonic acid and stimulated with ionophore A23187. Elevated glucose cultures released less radiolabeled products and less [14C]arachidonic acid. Analysis of cellular lipids revealed that elevated glucose reduced net loss of radiolabel from diacylphosphatidylethanolamine, did not affect early phosphatidylinositol hydrolysis, and increased net loss from diacylphosphatidylcholine and alkenylacylphosphatidylethanolamine. Uptake of radiolabel upon stimulation was examined to measure the role of reacylation on the diminished net release of radiolabel in elevated glucose cultures. Enhanced acylation of [3H]arachidonic acid into cellular lipids, especially PI, was observed in stimulated and resting cultures with elevated glucose. Further, pretreatment of the cultures with an acyltransferase inhibitor, thimerosal, prior to A23187 stimulation in radiolabeled cultures, abolished the effects of glucose on eicosanoid and arachidonic acid release. Differences in the ionophore-induced net loss of radiolabel from diacylphosphatidylethanolamine and phosphatidylinositol of the two glucose treatments were diminished by thimerosal exposure, while net loss of radiolabel from diacylphosphatidylcholine and alkenylacylphosphatidylethanolamine were unaffected. The data indicate that elevated glucose alters deacylation and enhances reacylation of arachidonic acid into endothelial cells and particularly into phosphatidylinositol. Enhanced reacylation may explain some of the altered lipid pathways that have been observed in experiments that elevate glucose concentrations or involve diabetes.

Acylation↗

Complications associated with the use of an infusion pump during knee arthroscopy.

This is a report of four complications from the use of an automated arthroscopy pump in 283 patients undergoing knee arthroscopy. The first patient had extravasation of fluid into the thigh, requiring discontinuation of the procedure. The second patient developed a compartment syndrome of the leg, necessitating a four-compartment fasciotomy of the leg. The third patient developed severe fluid extravasation into the anterior thigh compartment. A limited fasciotomy of the anterior thigh compartment was performed. The fourth patient developed moderate extravasation into the anterior part of the thigh and groin, necessitating discontinuation of pump irrigation and conversion to gravity irrigation to complete a partial medial meniscectomy. During a 15-month period, a complication rate of 1.4% from fluid extravasation during knee arthroscopy was noted. This review represents our initial experience with the infusion pump. No cases of fluid extravasation have occurred subsequently during a 12-month period.

Adult↗

Colonization factor antigen CFA/IV (PCF8775) of human enterotoxigenic Escherichia coli: nucleotide sequence of the CS5 determinant.

Human enterotoxigenic Escherichia coli isolates expressing the colonization factor antigen CFA/IV (previously designated PCF8775) produce plasmid-encoded CS5 fimbriae. The nucleotide sequence of the region encoding the major CS5 fimbrial subunit was determined. The subunit is synthesized as a precursor of 203 amino acids (20.85 kDa) with a mature protein of 181 amino acids corresponding to a size of 18.6 kDa. The CS5 subunit shows homology to the corresponding component of porcine enterotoxigenic E. coli F41, particularly within the signal sequence and at the carboxy terminus.

Amino Acid Sequence↗

Priming of anti-human immunodeficiency virus (HIV) CD8+ cytotoxic T cells in vivo by carrier-free HIV synthetic peptides.

The generation of antiviral cytotoxic T lymphocytes (CTLs) is a critical component of the immune response to viral infections. A safe and nontoxic vaccine for AIDS would optimally use a carrier-free synthetic peptide immunogen containing only components of HIV necessary for induction of protective immune responses. We report that hybrid synthetic peptides containing either a HIV envelope gp120 T-cell determinant (T1) or the envelope gp41 fusion domain (F) N-terminal to HIV CTL determinants are capable of priming murine CD8+, major histocompatibility complex class I-restricted anti-HIV CTLs in vivo. These data demonstrate that carrier-free, nonderivatized synthetic peptides can be used in vivo to induce anti-HIV CTL responses.

Amino Acid Sequence↗

The oac gene encoding a lipopolysaccharide O-antigen acetylase maps adjacent to the integrase-encoding gene on the genome of Shigella flexneri bacteriophage Sf6.

Lysogens of Shigella flexneri harbouring the temperate bacteriophage, Sf6, have been previously shown to undergo a serotype conversion due to O-acetylation of the O-antigen of the lipopolysaccharide. A partial physical map of the phage genome has been constructed. Analysis of the phage DNA suggests that the phage packages by a headful mechanism and that the mature DNA molecules are terminally redundant. Cloning of the PstI fragments of Sf6 enabled the region encoding the serotype conversion to be localized, showing that this was clearly phage-encoded. The gene was further localized by mutagenesis with Tn5 and the nucleotide sequence of the entire 2693-bp PstI fragment was determined. Two major open reading frames (ORFs) were found capable of encoding proteins of 44.1 and 37.2 kDa. The latter corresponds to the O-antigen acetylase and its gene has been designated oac. The oac gene is capable of converting Sh. flexneri serotypes X, Y, 1a and 4a to 3a, 3b, 1b and 4b, respectively. The Oac protein bears a high degree of homology to the NodX protein of Rhizobium leguminosarum suggesting that it, too, may be a sugar acetylase. The second ORF immediately upstream from oac corresponds to the bacteriophage Sf6 integrase responsible for chromosomal integration and is highly homologous to the integrases of Escherichia coli bacteriophages P4 and phi 80, but less closely related to those of P1, P2, P22, 186 and lambda.

Acetylesterase↗

Graded exercise testing and postthoracotomy complications.

A controversy exists over whether or not preoperative exercise testing can predict postthoracotomy complications. This study was designed to evaluate the usefulness of a presurgical exercise protocol in patients with lung disease, but no evidence of cardiac disease. Seventy patients underwent baseline pulmonary function testing and split function perfusion studies, when indicated, to calculate predicted postoperative pulmonary function. Noninvasive data were incrementally collected from 17 patients by using a treadmill exercise tolerance test that was designed to elicit maximal performance. Inhaled and exhaled gas flow and volume, the partial pressure of O2 and CO2, maximal O2 consumption (VO2max), and maximal minute ventilation (VE max) were measured. The breathing and heart rate reserves were calculated by standard formulae in an attempt to separate cardiac from pulmonary exercise limitation. Two patients had postoperative cardiopulmonary complications after thoracotomy and lung resection, and six patients had noncardiopulmonary complications. There was no significant prognostic relationship among VO2max, VE max, maximum O2 pulse, and the incidence of postoperative cardiopulmonary complications. The percentages of predicted VE max and predicted maximum heart rate were related to the occurrence of total complications, but not specifically to cardiopulmonary complications. The results emphasize the difficulty in attempting to exercise thoracotomy candidates with chronic lung disease to maximal performance. Excluding patients from further surgical consideration because of exercise limitation is not feasible based on these data.

Aged↗

The effects of capsular polysaccharide on the capacity of serum to support the killing of type 3 Streptococcus pneumoniae by human neutrophils.

To assess the effects of purified capsular polysaccharide from type 3 S. pneumoniae (PPS-3) on the capacity of serum to support pneumococcal killing by human neutrophils, varying concentrations of PPS-3 (0.01-100 micrograms/ml) were incubated (4 degrees C) with pooled serum for 30 min, and the resulting preparation, termed absorbed serum, was evaluated in bactericidal and phagocytic assays. The ability of serum to promote the killing of type 3 S. pneumoniae was significantly reduced at greater than or equal to 1.0 micrograms/ml PPS-3; similarly, serum absorbed with greater than or equal to 1.0 micrograms/ml PPS-2 failed to support the killing of type 2 S. penumoniae. However, the impact of these penumococcal polysaccharides was serotype specific, since the killing of type 3 S. pneumoniae was not impaired in serum absorbed with PPS-2, and the killing of type 2 S. pneumoniae was not attenuated in serum treated with PPS-3. The failure of serum absorbed with PPS-3 to promote the killing of type 3 S. pneumoniae was primarily a consequence of impaired bacterial ingestion; the reduction in phagocytosis was associated with parallel changes in superoxide anion release. The defects in phagocytosis and killing induced by PPS-3 were not associated with alterations in classical or alternative complement pathway activity; however, they were highly correlated with changes in serum antibody levels to the polysaccharide. The addition of polyclonal human IgG to serum treated with PPS-3 did not restore its capacity to support killing; however, preopsonization of the bacterium with the IgG preparation did partially correct the deficiency. Finally, neutrophils preincubated with serum containing greater than or equal to 10.0 micrograms/ml PPS-3 exhibited an impaired bactericidal activity against type 3 S. pneumoniae. Thus, these studies demonstrate that the presence of PPS-3 decreases the capacity of serum to support the killing of type 3 S. pneumoniae by absorbing immunoglobulins and by generating factors that interfere with neutrophil function.

Adult↗

In vitro assessment of chemotaxis by peripheral blood neutrophils from adult and senescent C57BL/6 mice: correlation with in vivo responses to pulmonary infection with type 3 Streptococcus pneumoniae.

To assess the effects of advanced age on the ability of circulating neutrophils to respond to biologically relevant chemoattractants, cells were isolated from the peripheral blood of pathogen and disease-free C57BL/6 mice and evaluated in a microchemotaxis chamber. The responses of granulocytes obtained from senescent mice (26-28 months) to the chemotactic peptide, FMLP, and to leukotriene B4 were similar to those found with cells from the younger animals (8-10 months). In contrast, the migration of neutrophils in response to sonicated type 3 Streptococcus pneumoniae was significantly greater with cells from the older animals. Similarly, the chemotactic response of neutrophils to zymosan-activated serum was greater with cells and serum from the senescent animals; however, the enhanced chemotaxis exhibited by granulocytes from the aged mice was a consequence of serum factors. Following the deposition of viable type 3 S. pneumoniae into the lower respiratory tract, the neutrophil influx at 24 h after challenge was significantly greater in the senescent mice; however, age-related differences in survival rates and LD50 were not detected. Thus, in the C57BL/6 mouse, senescence is not associated with deficiencies in the response of neutrophils in vitro to chemoattractants that contribute to lung host defense against the pneumococcus; further, in this murine strain, advanced age does not result in an attenuation of the pulmonary inflammatory reaction to infection with type 3 S. pneumoniae.

Aging↗

An assessment of the factors contributing to the killing of type 3 Streptococcus pneumoniae by human polymorphonuclear leukocytes in vitro.

To characterize the factors that contribute to the killing of type 3 S. pneumoniae, human neutrophils were obtained from healthy donors and incubated with viable organisms. In contrast to prior observations with other pneumococcal serotypes, killing was not detected when 10(6) colony forming units (cfu) were incubated at 37 degrees C for 2-4 hours with 10(6) neutrophils in the presence of 20-80% fresh autologous serum; further, pneumococcidal activity was not found when preopsonized bacteria and primed neutrophils were employed in the standard assay. However, when the bacterium to cell ratio was reduced to 1:100 and 1:1000, microbicidal action was detected; a 10-fold reduction in the number of viable bacteria was observed when 2 x 10(3) cfu were incubated with 2 x 10(6) neutrophils and 80% autologous serum at 37 degrees C for 4 hours. To assess the effects of serum factors on killing, bactericidal assays were performed in the presence of normal human serum (NHS), heat-inactivated human serum (HIHS) and absorbed human serum (AHS); heating reduced and absorption eliminated the capacity of serum to support killing. Studies performed with mutanolysin, an enzyme that lyses type 3 pneumococci, demonstrated that the effects of HIHS and AHS on bactericidal activity were highly correlated with alterations in the ability of the sera to support phagocytosis. Studies of neutrophil activation revealed changes in the production of superoxide anion that correlated well with phagocytosis and killing; however, the results of assays of leukotriene B4 generation and degranulation (beta-glucuronidase and lactoferrin release) were more variable. In mixing experiments, the capacity of HIHS to support killing was normalized with NHS; however, the ability of AHS to promote killing was not restored with HIHS or NHS. Thus, these studies demonstrate the relatively limited capacity of human serum to support the killing of type 3 pneumococci, and they emphasize the importance of killing assays in assessing interactions between the bacterium and neutrophils.

Blood Bactericidal Activity↗