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Biomedical subjects

M S Meyer

Publications and source records attributed to M S Meyer.

At least 19 recordsLinked to original sources

Linkage studies suggest a possible locus for developmental dyslexia on chromosome 1p.

Eight extended dyslexic families with at least four affected individuals were genotyped with twelve genetic markers spanning the Rh (rhesus factor) locus. Eleven of these markers were located on the short arm and the other was on the long arm of chromosome 1. Five theoretically derived phenotypes were used in the linkage analyses: 1) phonemic awareness; 2) phonological decoding; 3) rapid automatized naming; 4) single word reading; and 5) vocabulary. In addition, a lifetime diagnosis of dyslexia was used as a phenotype. Both parametric and non-parametric genetic analyses were completed. The results supported the importance of a putative locus on 1p. In addition, two-locus analyses assuming the interaction between a 1p locus and a 6p locus, previously shown to be of interest for dyslexia, were conducted. As a result, the nonparametric linkage (NPL) scores for rapid automatized naming and phonological decoding were significantly increased. In particular, the NPL scores for rapid automatized naming exceeded 5.0 for certain markers. These results provide strong evidence for separate but jointly acting contributions of the 1p and 6p loci to the reading impairments associated with rapid naming and suggestive evidence for a similar mechanism involving phonological decoding.

Adolescent↗

Chromosome 6p influences on different dyslexia-related cognitive processes: further confirmation.

In this study, which is a continuation and an extension of an earlier study, we enrolled two new families (N=31) and recruited more individuals from the previously ascertained families (N=56). The eight multiplex families (N=171) presented in this study were ascertained from a sample of adult probands whose childhood reading history is well documented through archival information. Six phenotypes were constructed to span a range of dyslexia-related cognitive processes. These phenotypes were (1) phonemic awareness (of spoken words); (2) phonological decoding (of printed nonwords); (3) rapid automatized naming (of colored squares or object drawings); (4) single-word reading (orally, of printed real words); (5) vocabulary; and (6) spelling (of dictated words). In addition, the diagnosis of lifelong dyslexia was established by clinical means. Genotyping was done with nine highly polymorphic markers from the 6p22.3-6p21.3 region. The results of two- and multipoint identity-by-descent and identity-by-state analyses supported the importance of a putative locus in the D6S464-D6S273 region for a number of dyslexia-related cognitive deficits.

Adolescent↗

Evaluating marrow margins for resection of osteosarcoma. A modern approach.

Intraoperative evaluation of bone marrow margins by frozen section analysis is a common practice in the surgical treatment of osteogenic sarcoma. The purpose of this study was to assess the clinical use of intraoperative marrow margin evaluation to rule out occult intramedullary tumor extension in osteosarcoma surgery. One hundred twenty-eight consecutive patients with high grade osteosarcoma diagnosed between 1988 and 1996 (Group 1) were reviewed retrospectively and compared with 92 consecutive patients treated from 1979 to 1984 (Group 2). Eighty-five patients in Group 1 met the inclusion criteria of having high grade intramedullary lesions of the long bones observed on preoperative magnetic resonance imaging evaluation of the lesion and intraoperative frozen section analysis of the bone marrow margin. Thirty-three patients in Group 2 met the same inclusion criteria with the exception of having preoperative magnetic resonance imaging. Ninety-two marrow margins in Group 1 and 33 marrow margins in Group 2 were evaluated by frozen section. All 92 marrow margins in patients in Group 1 were negative by frozen section analysis and permanent histologic analysis. Of the 33 marrow margins in patients in Group 2, three (9.1%) were reported positive for tumor. Of these, one was found to be a false positive result on permanent pathologic examination. In addition, one false negative frozen section result was found, which was positive for tumor on permanent pathologic examination. The difference in true positive results of marrow margins between Group 1 and Group 2 was statistically significant. Intraoperative marrow margin evaluation by frozen section is not mandatory with modern imaging techniques. Preoperative evaluation of tumor extent using magnetic resonance imaging and intraoperative evaluation of the specimen by the pathologist (done by bivalving the specimen) are reliable methods to ensure adequate surgical margins in most cases of conventional osteosarcoma of the long bones.

Adolescent↗

Susceptibility loci for distinct components of developmental dyslexia on chromosomes 6 and 15.

Six extended dyslexic families with at least four affected individuals were genotyped with markers in three chromosomal regions: 6p23-p21.3, 15pter-qter, and 16pter-qter. Five theoretically derived phenotypes were used in the linkage analyses: (1) phonological awareness; (2) phonological decoding; (3) rapid automatized naming; (4) single-word reading; and (5) discrepancy between intelligence and reading performance, an empirically derived, commonly used phenotype. Two-point and multipoint allele-sharing analyses of chromosome 6 markers revealed significant evidence (P < 10(-6)) for linkage of the phonological awareness phenotype to five adjacent markers (D6S109, D6S461, D6S299, D6S464, and D6S306). The least compelling results were obtained with single-word reading. In contrast, with chromosome 15 markers, a LOD score of 3.15 was obtained for marker D15S143 at theta = 0.0 with single-word reading. Multipoint analyses with markers adjacent to D15S143 (D15S126, D15S132, D15S214, and D15S128) were positive, but none reached acceptable significance levels. Chromosome 15 analyses with the phonological awareness phenotype were negative. Parametric and nonparametric linkage analyses with chromosome 16 markers were negative. The most intriguing aspect of the current findings is that two very distinct reading-related phenotypes, reflecting different levels in the hierarchy of reading-related skills, each contributing to different processes, appear to be linked to two different chromosomal regions.

Adolescent↗

Triple arthrodesis: a biomechanical evaluation of screw versus staple fixation.

The subtalar, talonavicular, and calcaneocuboid joints were internally fixed to simulate triple arthrodesis was performed on eight matched pairs of human cadaver feet. Feet were randomly assigned such that one specimen in each pair was internally fixed with cobalt-chrome staples and one specimen with stainless steel screws. Liquid metal strain gauges were placed in a perpendicular fashion across the three joints of each specimen. Each foot was then secured to the Shore Western Materials Test System where a series of 10 increasing eversion stresses across the foot was created. Displacement was measured at each joint with every increase in eversion stress. Our results show that there is no statistical difference in fixation strength between screws and staples at the talonavicular, calcaneocuboid, or subtalar joints (P = 0.862). Although many studies determining the strength to failure of different implants have been performed, shear stress and micromotion at the joint surfaces have not been evaluated, to our knowledge, and no single implant in this study has shown superior immobilization characteristics to recommend its use as the implant of choice in triple arthrodesis.

Arthrodesis↗

Congestive heart failure: meet the challenge.

Congestive heart failure is an increasingly common, complex disease process with far reaching consequences for patients and caregivers. Thorough knowledge of the pathophysiology, assessment, and management of congestive heart failure affords nurses the opportunity to improve patient functional status and quality of life.

Heart Failure↗

Prevention of stress gastritis with tissue preservation solution.

Stress gastritis frequently occurs in association with shock or sepsis. Gastric mucosal ischemia appears to be a key feature in these critically ill patients. The University of Wisconsin cold preservation solution (UWS) is an isoosmolar, nonglucose-based perfusate that minimizes hypothermia-induced cell swelling and prevents intracellular acidosis and oxygen-free radical injury, while providing high energy substrates for donor organs. In a prospective, single-blind study, 18 similar Sprague-Dawley rats were randomly divided to receive only 5 per cent dextrose and water (D5W) (Group 1) or a 50 per cent solution of D5W+UWS (Group 2) for 72 hours. At the end of 72 hours the animals were stressed by the cold-restraint model. The mean number of ulcers for Group 2 was nearly half that of Group 1. Also, Group 2 had a significantly lower mean total ulcer length (P less than 0.005) and ulcer index (P less than 0.05). Most of Group 2 had mild gastritis changes (grade 0 to 1), while more than half of Group 1 had severe gastritis (grade 3). Gastric mucosal pH was similar for both groups. Topically applied UWS appears to reduce the severity and incidence of stress gastritis in this experimental model. Because mucosal pH values were similar, it is thought that UWS may alter the effects of gastric mucosal ischemia at a cellular level.

Adenosine↗

Biochemical and biomechanical properties of avian callus after local administration of dihydroxylated vitamin D metabolites.

In vitamin D-fed chicks 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 were implanted into experimentally-produced fractures of the mid-tibia. The mechanical and biochemical properties of the tibia were evaluated for two weeks, including torsion tests, measurement of alkaline phosphatase activity, 45Ca incorporation, and Ca2+ content. Both dihydroxylated metabolites of vitamin D3 had a direct effect on endochondral bone formation. 24,25(OH)2D3 strengthened the callus, and raised alkaline phosphate activity in the first seven days after fracture. 1,25(OH)2D3 decreased the strength of the callus concomitant with a reduction in 45Ca incorporation. It is suggested that local application of 24,25(OH)2D3 into fractures may accelerate healing and prevent non-union.

24,25-Dihydroxyvitamin D 3↗

Mechanical, biochemical, and structural effects of vitamin D deficiency on the chick heart.

The effects of vitamin D deprivation on the chick heart were investigated from three aspects: cardiac contractility (+/- dP/dT), intracellular high-energy phosphorus compounds, and structural differences. Four-week-old vitamin D-deficient chicks were divided into four groups: Group A served as the normal group and received subcutaneous injections of cholecalciferol; Groups B and C were vitamin D-deficient hearts but perfused differently; Group D received daily subcutaneous injections of 5 micrograms of 1,25(OH)2D3. When the isolated spontaneously beating hearts (modified Langendorff preparation) were perfused with Krebs-Henseleit (KH) solution containing a calcium concentration of 2.5mM, the myocardial contractility of the vitamin D-deficient hearts was significantly increased when compared with group A. After the isolated heart had beaten for one hour, the myocardial contractility in the vitamin D-deficient hearts was found to decline to significantly lower values. Presacrifice administration of 1,25(OH)2D3 improved cardiac performance. Vitamin D deficiency resulted in an enhanced rate of decline of the intracellular high-energy phosphorus compounds. No differences were found in the microscopic study. These observations suggest that vitamin D has a role in cardiac function.

Adenosine Triphosphate↗

The effect of disodium ethane-1-hydroxy-1,1-diphosphonate on the metabolism of calcitriol in chicks.

Decreased intestinal absorption of Ca2+ occurs in response to treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP). The effect is due to decreased 1-hydroxylation of calcidiol (25-hydroxycholecalciferol) in the kidney. In an attempt to establish whether impairment of vitamin D metabolism at steps beyond kidney hydroxylation occurs due to treatment with EHDP, chicks were depleted of vitamin D and were treated with calcitriol (1,25-dihydroxycholecalciferol) as their sole source of the vitamin. The chicks were then divided into two groups, one being treated with EHDP while the second group served as control. Intestinal absorption of Ca2+ in the EHDP-treated group was found to be impaired, along with decreases in concentrations of calbindin D28K (the 28,000-Mr vitamin D-dependent Ca2+-binding protein). When the chicks were dosed with [3H]calcitriol, significantly lower concentrations of the sterol were detected in the duodena of EHDP-treated birds. Measurement of levels of receptors for calcitriol in duodena showed no difference between groups, but levels of calcitriol in sera were considerably lower in the EHDP-treated group along with the elevated biliary and urinary excretion of glucuronidated conjugates. It is therefore concluded that treatment with EHDP results in increased catabolism of calcitriol in addition to the known suppression of the renal production of the hormone.

Animals↗

Increased 25-hydroxyvitamin D levels in portal blood following cholecystokinin injection in the dog.

To establish whether an enterohepatic circulation of the metabolites of vitamin D exists, polyethylene catheters were cannulated into the portal vein of dogs. The dogs were then starved for 24 h and injected with cholecystokinin (CCK) to induce gall bladder contraction. At various time intervals thereafter blood samples were collected from the portal and the saphena veins, and sera prepared and analyzed for the metabolites of vitamin D. The serum levels of 25-hydroxyvitamin D [25(OH)D] were found to be significantly higher in the portal blood when compared with levels in peripheral blood following CCK injection. Since portal blood collects nutrients absorbed from the gut and as the dogs were starved for 24 h prior to blood collection, the only source of the increased concentrations of 25(OH)D in portal blood is likely to be bile. These findings support the notion that an enterohepatic circulation of 25(OH)D does exist under normal physiological conditions.

Animals↗

Fecal loss of cholecalciferol in gastrectomized rats.

Rats were gastrectomized, and the intestinal absorption and fecal excretion of cholecalciferol were studied following the administration of radioactive cholecalciferol, either by subcutaneous injection or with the aid of a gastric tube. From measurements of radioactivity in feces and sera it has been possible to establish that gastrectomy in rats results in impaired intestinal absorption and increased fecal excretion of cholecalciferol. These findings indicate that gastrectomy alters the nutritional status of vitamin D, and may explain the high incidence of osteomalacia as a complication of gastrectomy.

Animals↗

Intestinal loss of vitamin D3 metabolites in rats with cirrhosis of the liver.

The metabolism of cholecalciferol (vitamin D3) was studied in cirrhotic and in control rats that were either depleted of or supplemented with vitamin D3. The vitamin was supplemented by s.c. injections of radiolabeled cholecalciferol at doses which meat the daily nutritional requirements of rats. Excretion of vitamin D3 metabolites in the feces of the cirrhotic rats was greater than that in the control rats. Fecal excretion consisted mainly of vitamin D3 ester the unchanged vitamin D3 and 25-hydroxyvitamin D3. It is suggested that one of the causes for vitamin D3 depletion in cirrhosis of the liver is fecal loss.

Animals↗

Metabolism of cholecalciferol in land snails.

1. Radioactively labelled cholecalciferol was injected into the land snails Levantina hiersolyma and Theba pisana. Three metabolites (C, D and E), more polar than cholecalciferol, were found. 2. Metabolite C was found to be identical with 25-hydroxycholecalciferol. On injection of 25-hydroxy[26,27-3H]cholecalciferol, metabolite E was predominantly formed. Metabolite D was predominantly formed from cholecalciferol. Metabolites D and E differ from any known cholecalciferol metabolites. 3. The intestine was found to be the tissue capable of carrying out the transformation of 25-hydroxycholecalciferol into metabolite E. 4. 25-Hydroxycholecalciferol and metabolite E were localized in the digestive gland of the snail, the tissue responsible for the absorption of Ca2+ and its storage. Metabolite D was not localized in any specific tissue.

Animals↗

Low levels of serum calcium, phosphorus and plasma 25-hydroxy vitamin D in cirrhosis of the liver.

In a retrospective analysis of 78 patients with liver cirrhosis, we found low serum levels of calcium and phosphorus. The low calcium levels showed a better correlation with high activity of aspartate aminotransferase than with low levels of albumin. In addition, there was a relationship between low calcium and low phosphorus levels. Therefore, factors other than, and in addition to, hypoalbuminemia seem to be responsible for the low calcium and phosphorus levels in cirrhosis patients. Although low levels of serum 25-hydroxyvitamin D were found in 23 of our patients, there was no indication that hypovitaminosis D was causative factor in the hypocalcemia and hypophosphatemia.

Aspartate Aminotransferases↗