Search PubMed⌕ Search

Biomedical subjects

K Young

Publications and source records attributed to K Young.

At least 37 records · Page 2Linked to original sources

Prion proteins with different conformations accumulate in Gerstmann-Sträussler-Scheinker disease caused by A117V and F198S mutations.

Gerstmann-Sträussler-Scheinker disease (GSS) is characterized by the accumulation of proteinase K (PK)-resistant prion protein fragments (PrP(sc)) of approximately 7 to 15 kd in the brain. Purified GSS amyloid is composed primarily of approximately 7-kd PrP peptides, whose N terminus corresponds to residues W(81) and G(88) to G(90) in patients with the A117V mutation and to residue W(81) in patients with the F198S mutation. The aim of this study was to characterize PrP in brain extracts, microsomal preparations, and purified fractions from A117V patients and to determine the N terminus of PrP(sc) species in both GSS A117V and F198S. In all GSS A117V patients, the approximately 7-kd PrP(sc) fragment isolated from nondigested and PK-digested samples had the major N terminus at residue G(88) and G(90), respectively. Conversely, in all patients with GSS F198S, an approximately 8-kd PrP(sc) fragment was isolated having the major N terminus start at residue G(74). It is possible that a further degradation of this fragment generates the amyloid subunit starting at W(81). The finding that patients with GSS A117V and F198S accumulate PrP(sc) fragments of different size and N-terminal sequence, suggests that these mutations generate two distinct PrP conformers.

Amyloid↗

Transcatheter intraarterial infusion of rt-PA for acute lower limb ischemia: results and complications.

PURPOSE: To determine the success and complication rates of intraarterial recombinant tissue-type plasminogen activator (rt-PA) infusion for the treatment of acute lower extremity artery and bypass graft occlusions. MATERIALS AND METHODS: The results of 74 limbs in 70 patients (mean age, 66 y) treated with catheter-directed rt-PA infusion for the treatment of acute lower extremity ischemia were retrospectively evaluated. The group included 42 bypass grafts and 32 native arteries. All limbs were viable at presentation. The mean duration of symptoms was 11.9 days. rt-PA was infused for a mean of 27.9 hours for a mean total dose of 38.7 mg. Initial infusion rates of 3-6 mg/h were lowered to a preferred rate of 1.5 mg/h. Thrombolytic success was defined as 95% thrombolysis of an occluded segment with return of antegrade flow. Major bleeding complications were defined as any hemorrhagic event leading to surgery, extended or unexpected hospitalization, transfusion, death, intracranial hemorrhage, or a decrease in hemoglobin of 5 g/dL or in hematocrit of 15%. Thirty-day mortality and amputation rates were calculated. Patient characteristics and infusion parameters were evaluated as to whether they contributed to thrombolytic success or major bleeding events. RESULTS: Thrombolytic success was achieved in 64 limbs (86%). Major bleeding complications occurred in 33 (47%) patients. In 22 of these patients, bleeding occurred at a vascular puncture site, whereas remote bleeding occurred in seven patients. Remote bleeding complications included two retroperitoneal hematomas, two rectus sheath hematomas, one lower gastrointestinal hemorrhage, one episode of hemoptysis, and one dehiscence of a femoral-popliteal bypass graft revision. No parameters were found to be predictive of thrombolytic success, whereas a negative history of smoking, increasing duration of infusion, and a low preprocedural ankle-brachial index (ABI) were found to be associated with major hemorrhagic events. Four patients (6%) underwent amputation and one patient (1%) died, resulting in a 30-day amputation-free survival rate of 93%. CONCLUSION: Catheter-directed rt-PA infusion is effective in achieving thrombolysis. Despite a significant number of bleeding complications, 30-day mortality and amputation rates were favorable. Nonetheless, complication rates related to bleeding were not trivial and further evaluation with use of variable dosing regimens is indicated.

Adult↗

A brief report on the Penn Inventory for posttraumatic stress disorder.

In this report we provide normative data for the Penn Inventory for posttraumatic stress disorder for men and women who were referred to a specialist outpatient clinic following a range of traumatic events. Data are provided from clinical assessment of 80 people. There was no significant difference between male and female scores. Using the Clinician Administered PTSD Scale to ascertain diagnostic status and Hammarberg's cut-off criterion of 35, the Penn Inventory showed a sensitivity of .90 for male participants and .89 for female participants and a specificity of .55 for male participants and .67 for female participants. The Penn Inventory correlated highly with other measures of psychological distress. We discuss that the Penn Inventory may be best used as a screening instrument or measure of change of general mental well-being after trauma, rather than a diagnostic tool for specific traumatic stress symptoms.

Adult↗

High detection rate for BRCA2 mutations in male breast cancer families from North West England.

33 families with a history of male breast cancer aged 60 or less or with a family history of male and female breast cancer were screened for the presence of BRCA2 mutations. 12 pathogenic BRCA2 mutations were identified (36%) in samples from an affected family member. All mutations segregated with disease where it was possible to check. Of the 14 families fulfilling BCLC criteria, 9 (64%) had mutations whilst only 3/16 (19%) of male breast cancer patients with less significant female breast cancer family history having a mutation. All 3 families with ovarian cancer and 3 families with multiple male breast cancer cases had BRCA2 mutations. These data are a further guide to how to prioritise samples for BRCA2 mutation analysis.

Adult↗

Isolation, cloning and functional characterization of porcine mannose-binding lectin.

Binding of mannose-binding lectin (MBL), a C-type lectin, and its associated serine proteases, MASP-1 and MASP-2, to cell surface carbohydrates activates the lectin complement pathway. As MBL plays an important role in innate immunity, it has been cloned and characterized in several species. While the pig may be used as a source of organs/tissues for xenotransplantation, little is known about its MBL, thus, we report the isolation of three monomeric forms of MBL from porcine serum. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Coomassie staining of reduced porcine MBL revealed the presence of three monomeric forms with approximate molecular masses of 30 000, 32 000 and 34 000. Protein sequencing identified these monomeric forms as one single protein, suggesting post-translational modification. Western blot analysis demonstrated the cross-reactivity of anti-human MBL polyclonal antibody with porcine MBL. A full-length porcine liver MBL cDNA was isolated and the predicted amino acid sequence exhibited 64.9% identity with human MBL and 50.2% and 56.7% identity with rat A and C MBL, respectively. Furthermore, Northern blot analysis demonstrated the presence of a single ( approximately 1.4-1.6 kilobase pair) transcript in porcine liver. Addition of purified porcine MBL to MBL-deficient human sera augmented N-acetylglucosamine inhibitable C3 deposition to mannan-coated plates in a dose-dependent manner. Taken together, these data demonstrate that porcine and human MBL are highly conserved, sharing structural and functional characteristics.

Amino Acid Sequence↗

Measurement of first-ray mobility in normal vs. hallux valgus patients.

Hypermobility of the first ray is one causative factor in development of hallux valgus and an important factor in the treatment of hallux valgus, but measuring first-ray motion is difficult. There are two known ways of measuring first-ray motion. One is measuring the bony angle on the lateral foot X-ray using a modified Coleman block. The other is using devices. However, neither is suitable for clinical application. We introduce a simple, fast and easy way of measuring first-ray range of motion. Using this method, we compared the first-ray motion between a normal group and a hallux valgus group. Forty normal and 60 hallux valgus patients were included in the measurement. We measured the first-ray range of motion in the following way: with one hand we held the 2nd, 3rd, 4th, and 5th rays at the metatarsal head level with a simple right-angled indicator. With the other hand, we held the first ray at the metatarsal head level using a simple right-angled device, such as a scale. Keeping the other rays fixed, we moved the first ray up and down and recorded the average distance (d) 10 times to reduce intra-measurement differences. We also measured and recorded the first metatarsal length (L) on the anteroposterior foot X-ray film. Finally, we calculated the first-ray range of motion (alpha) using the above data. We also measured the hallux valgus angle and intermetatarsal angle in the hallux valgus patient group. With this method, the average first-ray motion was 10.3 degrees in the normal group and 12.9 degrees in the hallux valgus patient group. If we define 14 degrees, (that is, above the 95th percentile in the normal group) as having hypermobility, 38% of hallux valgus patients had first ray hypermobility. There was no correlation between first-ray hypermobility and either hallux valgus angle or intermetatarsal angle.

Adult↗

Department of Veterans Affairs Cooperative Studies Program genetic linkage study of schizophrenia: ascertainment methods and sample description.

To help clarify the genetics of schizophrenia, the Department of Veterans Affairs Cooperative Studies Program has completed data collection for a genetic linkage study of schizophrenia. This article describes the methodological details of the data collection. Subsequent articles will describe the results of our genome scan, which is now in progress. The data collection protocol included the Diagnostic Interview for Genetic Studies, the Family Interview for Genetic Studies, a review of medical records, and the collection of blood for transformation into lymphoblast cell lines. Among relatives of schizophrenic probands, we assessed auditory attention and verbal memory with neuropsychological tests. Among the 166 families ascertained for the study, 143 had a single affected sib-pair, 17 had three affected siblings, one had five affected siblings and five had two sets of affected siblings. There was a total of 216 affected sib-pairs in these families. Using the n-1 rule, these families contain 188 independent affected sib-pairs.

Adult↗

Interrelations between plasma homocysteine and intracellular S-adenosylhomocysteine.

S-Adenosylhomocysteine, a potent intracellular methylation inhibitor, is suggested as a potential mediator for hyperhomocysteinemia-related vascular changes. We investigated the effect of acute and chronic hyperhomocysteinemia on intracellular S-adenosylhomocysteine and S-adenosylmethionine in rats and humans. Elevated plasma homocysteine in rats infused with homocysteine produced an increase in S-adenosylhomocysteine (P < 0.001) but not S-adenosylmethionine levels (P > 0.05) in various rat tissues. However intraerythrocyte S-adenosylhomocysteine and S-adenosylmethionine levels were not changed in homocysteine-infused rats and human subjects with experimentally acute hyperhomocysteinemia by methionine loading test. In contrast, erythrocyte S-adenosylhomocysteine levels were significantly higher in chronic renal failure patients, who had chronically elevated plasma homocysteine levels, than in either vascular disease patients or healthy controls (P < 0.05). In conclusion, acute hyperhomocysteinemia can increase intracellular S-adenosylhomocysteine levels in tissues actively involved in homocysteine metabolism. The findings are relevant to homocysteine-related endothelial dysfunction since S-adenosylhomocysteine modulates endothelial cell apoptosis.

Adult↗

Proton NMR chemical shifts and coupling constants for brain metabolites.

Proton NMR chemical shift and J-coupling values are presented for 35 metabolites that can be detected by in vivo or in vitro NMR studies of mammalian brain. Measurements were obtained using high-field NMR spectra of metabolites in solution, under conditions typical for normal physiological temperature and pH. This information is presented with an accuracy that is suitable for computer simulation of metabolite spectra to be used as basis functions of a parametric spectral analysis procedure. This procedure is verified by the analysis of a rat brain extract spectrum, using the measured spectral parameters. In addition, the metabolite structures and example spectra are presented, and clinical applications and MR spectroscopic measurements of these metabolites are reviewed.

Acetic Acid↗

Confidence images for MR spectroscopic imaging.

Automated spectral analysis and estimation of signal amplitudes from magnetic resonance data generally constitutes a difficult nonlinear optimization problem. Obtaining a measure of the degree of confidence that one has in the estimated parameters is as important as the estimates themselves. This is particularly important if clinical diagnoses are to be based on estimated metabolite levels, as in applications of MR Spectroscopic Imaging for human studies. In this report, a standard method of obtaining confidence intervals for nonlinear estimation is applied to simulated data and short-TE clinical proton spectroscopic imaging data sets of human brain. So-called "confidence images" are generated to serve as visual indicators of how much trust should be placed in interpretation of spatial variations seen in images derived from fitted metabolite parameter estimates. This method is introduced in a Bayesian framework to enable comparison with similar techniques using Cramer-Rao bounds and the residuals of fitted results.

Bayes Theorem↗

Sentinel node biopsy and internal mammary lymphatic mapping in breast cancer.

BACKGROUND: Currently outer quadrant breast tumors are not felt to have significant drainage to the internal mammary nodal chain. We evaluated the incidence of internal mammary sentinel nodes (IMSN) found with lymphoscintigraphy for all breast quadrants. METHODS: Eighty women were prospectively studied by technitium-sulfur colloid injection, nuclear medicine imaging, and intraoperative gamma probe identification of sentinel nodes. IMSN detected were surgically removed. RESULTS: Ten of 80 ( 12%) patients had IMSN identified in addition to axillary sentinel nodes (AXSN). Four tumors were located medially, 6 (60%) were in the outer quadrants. Metastatic disease was present in 3 of 10 women. Patients with positive IMSN also had positive AXSN. CONCLUSIONS: Patients undergoing lymphatic mapping for the management of breast cancer should have radiolabelled tracer and gamma probe sentinel node identification regardless of tumor location in the breast.

Biopsy↗

Generalising to theory: the use of a multiple case study design to investigate needs assessment and quality of care in community nursing.

This paper outlines the detail of the case study method used in a project commissioned by the English National Board for Nursing, Midwifery and Health Visiting (ENB) to investigate the changing educational needs of community nurses with regard to needs assessment and quality of care in the context of the NHS and Community Care Act, 1990. It explains the methodological procedures and analytic processes which led to integration of data across the whole study, focusing on the role of a prior theoretical framework in case study design. Recently qualified practitioners (health visitors and district nurses) were observed during a regular shift (N=134 visits), concentrating on their practice of assessing needs, and on liaison and collaboration within teams and across sectors. They were interviewed after the observation period (N=33 practitioners), to determine the extent of formality they attached to each assessment, and elicit information about aspects which may be embedded in everyday practice as well as those recorded for explicit requirements.The preliminary analysis resulted in the modification of a model for assessing service quality, and identified various points where a 'policy-practice gap' might arise between policies and practice in both the health service and education. The practicalities of operationalising a multiple case study design into research are highlighted, and the mechanism for 'generalising to theory' illustrated.

Community Health Nursing↗

Assessment of a polyester-covered nitinol stent in an atherosclerotic swine model.

PURPOSE: To evaluate the short-term patency and healing characteristics of the Cragg EndoPro covered stent in an atherosclerotic model as one of the Food and Drug Administration requirements before possible approval of the device for human use in the United States. MATERIALS AND METHODS: Seventeen self-expanding stent-grafts were placed in the aorta and right and left iliac arteries of six Yucatan microswine exposed to a regimen of accelerated atherosclerosis. The stent-grafts were constructed from nitinol wire formed into a tubular zigzag configuration. The stent frame was covered by a thin woven polyester fabric tube, with medium permeability, available in multiple diameters and lengths. The animals were killed at 24 hours, 3 months, and 6 months. Assessment was done by angiography and histology. RESULTS: All stents were patent immediately after deployment. Two stents were occluded at follow-up, indicating an 88% patency rate. Minor lumen narrowing was found at the follow-up intervals. Histologic examination revealed a mixture of mature and immature endothelial cells lining both the native and stented regions in all vessels examined. The new endoluminal surface was composed primarily of fibrocollagen and elastic fibers and smooth muscle cells. Intimal thickness was inversely correlated to medial thickness. Medial compression with atrophy was observed routinely with rare necrosis. Complete tissue ingrowth was seen by 3 months. The degree of vascular inflammation increased over time, as well as the foreign body giant cell reaction to the polyester fabric. CONCLUSION: The patency rate does not appear to be better than that with angioplasty or noncovered stent placement in the studied time frame. The progressive vascular inflammatory changes noted should be further investigated in longer-term animal trials to ensure its safety in humans because this device is meant to be permanent.

Alloys↗

A method for establishing primary cultures of human gastric epithelial cells.

Long-term culture of human gastric epithelial cells has been difficult, and at present no normal human gastric epithelial cell lines are readily available. As part of our experiments to study pathogenesis of H. pylori, a bacterium that infects the stomach, we developed methods to culture normal human gastric epithelial cells. Primary cultures of human gastric epithelial cells can be established from gastric biopsies taken at upper G.I. endoscopy. Enzymatically isolated gastric epithelial-like cells are present in tight colonies on culture dishes within 24 hours of placing the cells in culture. Cells isolated stain positively for cytokeratin and produce neutral mucins, indicating that they are mucin secreting epithelial cells, consistent with gastric epithelial cells. Epithelial cells can be maintained up to 4 weeks in culture with evidence of DNA synthesis up through the first week of culture.

Biopsy↗

A taxonomy of needs assessment, elicited from a multiple case study of community nursing education and practice.

The role and expectations of community nurses in carrying out needs assessments changed when an internal quasi-market was introduced to the British health service under the National Health Service (NHS) & Community Care Act 1990. This paper reports on a study commissioned by the English National Board for Nursing, Midwifery and Health Visiting (ENB) to investigate the changing educational needs of community nurses with regard to needs assessment in the context of this legislation. A multiple case study design was utilized and four cases identified, incorporating the geographical variation in England. Recently qualified practitioners (health visitors and district nurses) were observed during a regular shift (n=134 visits), concentrating on their practice of assessing needs, and on liaison and collaboration within teams and across sectors. Participants were interviewed after the observation period (n=33 practitioners), to determine the extent of formality they attached to each assessment, and to elicit information about aspects which may be embedded in everyday practice. Single and multiple case analyses across the four cases used an iterative process of pattern-matching, replication logic and explanation building. The preliminary analysis yielded a descriptive 'taxonomy' which could serve as a basis for classifying the variants of needs assessment and help to clarify the whole phenomenon. When applied further to the data, this revealed the complex interactions between the different ideals (relating to policy, nursing and ascribed worth), the various types (purpose, formality/specificity and complexity) and timing (in relation to client, service and practice issues) within needs assessment.

Community Health Nursing↗

The effect of vitamin-mineral supplementation on the intelligence of American schoolchildren: a randomized, double-blind placebo-controlled trial.

CONTEXT: Many medical, nutrition, and education professionals have long suspected that poor diet impairs the academic performance of Western schoolchildren; academic performance often improves after improved diet. However, others have suggested that such academic gains may be due to psychologic effects rather than nutrition. To resolve this issue, two independent research teams conducted randomized trials in which children were given placebos or low-dose vitamin-mineral tablets designed to raise nutrient intake to the equivalent of a well-balanced diet. Both teams reported significantly greater gains in nonverbal intelligence among the supplemented groups. The findings were important because of the apparent inadequacy of diet they revealed and the magnitude of the potential for increased intelligence. However, none of the ten subsequent replications, or the two original trials, were without limitations leaving this issue in controversy. OBJECTIVES: To determine if schoolchildren who consume low-dose vitamin-mineral tablets will have a significantly larger increase in nonverbal intelligence than children who consume placebos in a study that overcomes the primary criticisms directed at the previous 12 controlled trials. DESIGN: A double-blind, placebo-controlled trial using stratified randomization within each teacher's class based on preintervention nonverbal intelligence. SETTINGS AND SUBJECTS: Two "working class," primarily Hispanic, elementary schools in Phoenix, Arizona, participated in the study. Slightly more than half the teachers in each school distributed the tablets daily to 245 schoolchildren aged 6 to 12 years. INTERVENTION: Daily vitamin-mineral supplementation at 50% of the U.S. daily recommended allowance (RDA) for 3 months versus placebo. OUTCOME MEASURES: Post-test nonverbal IQ, as measured by the Wechsler Intelligence Scale for Children-Revised (WISC-R), while controlling for pretest nonverbal IQ as a covariate. FOUR MAIN RESULTS: First, a significant difference of 2.5 IQ points (95% CI: 1.85-3.15) was found between 125 children given active tablets and 120 children given placebo tablets (p = 0.038). Second, this finding is consistent with the mean 3.2 IQ point net gain found in the 12 similar but less rigorous studies. Third, a significantly higher proportion of children in the active group gained 15 or more IQ points when compared to the placebo group (p < 0.01). Fourth, although 81 matched pairs produced no difference at all in nonverbal IQ gain, the modest 2.5 IQ point net gain for the entire sample can be explained by the remaining 24 children who took active tablets, and had a 16 point higher net gain in IQ than the remaining 19 placebo controls. CONCLUSIONS: This study confirms that vitamin-mineral supplementation modestly raised the nonverbal intelligence of some groups of Western schoolchildren by 2 to 3 points but not that of most Western schoolchildren, presumably because the majority were already adequately nourished. This study also confirms that vitamin-mineral supplementation markedly raises the non-verbal intelligence of a minority of Western schoolchildren, presumably because they were too poorly nourished before supplementation for optimal brain function. Because nonverbal intelligence is closely associated with academic performance, it follows that schools with children who consume substandard diets should find it difficult to produce academic performance equal to those schools with children who consume diets that come closer to providing the nutrients suggested in the U.S. RDA. The parents of schoolchildren whose academic performance is substandard would be well advised to seek a nutritionally oriented physician for assessment of their children's nutritional status as a possible etiology.

Arizona↗