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Biomedical subjects

D Walker

Publications and source records attributed to D Walker.

At least 37 records · Page 2Linked to original sources

Analysis of hepatitis C virus genome in patients with autoimmune hepatitis type 2.

BACKGROUND/AIMS: Hepatitis C virus (HCV) RNA is detectable in a proportion of patients with autoimmune hepatitis type 2, which is characterized by liver-kidney microsomal antibodies (LKM). Therefore, the genotype and sequence of HCV were studied in these patients. METHODS: Sera from 43 LKM-positive and anti-HCV-positive patients (15 from Germany and 28 from Italy) and 82 LKM-negative and anti-HCV-positive patients (57 from Germany and 25 from Italy) were examined. RESULTS: Genotyping revealed that the rate of genotype III HCV according to Okamoto's classification in patients with LKM antibody-positive autoimmune hepatitis type 2 was higher than in LKM-negative patients (22.0% vs. 2.4%; P < 0.05). This was because of an increase of genotype III in our patients from Italy. No HCV mutations were found that show a closer sequence homology to cytochrome P450IID6, the major LKM-1 antigen. Deletions in the envelope and nonstructural region 5 were found. CONCLUSIONS: Because a specific HCV sequence is not associated with the induction of LKM-1 autoantibodies, future research must focus on host factors and possibly additional environmental factors.

Adult

QRST changes during and after percutaneous transluminal coronary angioplasty.

This study reports preliminary results on 45 patients who underwent percutaneous transluminal coronary angioplasty (PTCA); 120-lead data (including the 12-lead standard electrocardiogram [ECG]) were recorded before, during, and after balloon inflation. Twenty-one patients underwent PTCA for left anterior descending coronary disease, 13 for right coronary artery disease, and 10 for left circumflex; 1 patient had combined left anterior descending and right coronary artery disease. In each patient, voltage data recorded during the various phases of the procedure were compared with the patient's own baseline data. In 18 patients, 120 leads were also recorded 24 hours after PTCA. In this study, the usefulness of the standard 12-lead ECG was investigated in locating the coronary artery being occluded, in elucidating the mechanisms of the QRS changes, and in identifying changes occurring 24 hours after completion of the procedure. Results indicate that the observation of ST elevation in the 12-lead ECG may lead to ambiguous interpretation. Also, limiting observation to ST-T patterns alone instead of including QRS changes further hampers correct identification of the involved vessel. QRS modifications during inflation are interpreted as conduction disturbances, although other mechanisms are evoked: study of surface maps may contribute to the understanding of these mechanisms. Changes present 24 hours later are visible in the standard leads, but again, in the absence of the thoracic potential distribution, these are difficult to interpret. These changes were different from those observed after cessation of inflation at the end of the procedure. It is hypothesized that next-day changes may reflect reperfusion injury and/or represent myocardial stunning. Presence of injury and reversibility of changes require further investigation. Also, biochemical markers such as creatine kinase-MB mass, creatine kinase-MB activity, myoglobin, and troponin-T may help elucidate the significance of these findings.

Angioplasty, Balloon, Coronary

Strategies for state statutory language changes granting fully independent nurse practitioner practice.

For nurse practitioners (NPs) to be considered as a critical component of health care reform, they must change their state statutes to permit independent practice. This can be accomplished by plenary prescriptive authority including controlled substances. This article provides a summary of NP scope of practice and prescriptive privileges to date, together with a discussion of the strong statutory language used by Alaska and New Mexico with regard to independent practice. Comparisons of model independent scope and prescriptive authority statutory language are discussed along with prevalent opposition arguments, appropriate practitioner titles, and an enumeration of strategies for effective lobbying.

Alaska

Effect of hyperthermia on uterine and umbilical blood flows in pregnant sheep.

Uterine and umbilical blood flows were measured in pregnant sheep (125-142 days gestation) under normothermic and hyperthermic conditions using the Fick principle with [14C]antipyrine as the indicator. Exposure of the sheep to an ambient temperature of 43 +/- 1 degrees C (25-30% relative humidity) for 8 h increased maternal and fetal core temperatures 1.19 +/- 0.15 and 1.39 +/- 0.12 degrees C respectively. Maternal hyperventilation caused a significant decrease of both maternal and fetal arterial partial pressure of CO2 (Pa,CO2) and increase of arterial pH. Uterine blood flow increased significantly during the hyperthermia (+54.2 +/- 14.1%), the increase being correlated with the magnitude of the decrease of maternal Pa,CO2 (r = -0.84, P < 0.05) but not with the increase of maternal core temperature. The increase of uterine blood flow was not associated with a concomitant increase in the placental clearance of [14C]antipyrine, a result which could arise if the increase of blood flow was non-placental (i.e. did not occur within the cotyledons), or occurred through uterine arteriovenous shunts during the period of heat stress. Hyperthermia was not associated with a significant change of umbilical blood flow, placental transfer of glucose, or fetal glucose uptake. Since the loss of heat from the fetus occurs mainly across the placenta, we speculate that the apparent increase of uterine blood flow during maternal hyperthermia has an adaptive significance by maintaining conductive heat flux in a fetomaternal direction, even though cotyledonary (placental) blood flows did not increase.

Animals

Does genetic anticipation occur in familial rheumatoid arthritis?

OBJECTIVE: To determine if there is evidence for genetic anticipation in rheumatoid arthritis (RA) by analysing the possibility that parental disease status and age at proband conception influence the age of onset and disease severity of the proband. METHOD: RA outpatients were identified and data were also taken from Newcastle multicase RA pedigrees. Comparisons of age of onset and parental age at proband conception were made for pedigrees grouped according to the disease status of the parents. Correlation coefficients and linear regression models were calculated for the age of RA onset in the probands. Measures of disease severity were compared in RA mother-proband pairs. RESULTS: The results were similar in both the outpatient (n = 153) and multicase pedigree (n = 15) samples. Significant results were confined to pedigrees in which the mother had RA (20 of the outpatient probands and seven of the multicase group). Probands in these sibships had a younger age of RA onset than their affected mothers (38.3 years (95% confidence interval (CI) 33.8 to 42.8) versus 53.7 (47.3 to 60.0) (p = 0.002) in the outpatient sample; 32.4 years (25.3 to 39.6) versus 43.4 years (29.0 to 57.9) (p = 0.1) in the multicase pedigrees). In the maternal RA group, both the maternal and paternal age at proband conception showed significant negative correlations (r = -0.65, p = 0.002 and r = -0.60, p = 0.005, respectively in the outpatient sample) and linear regression coefficients with age of proband disease onset. In seven affected mother-proband pairs, the probands had a tendency to more severe disease, despite shorter disease duration and younger age. CONCLUSIONS: This preliminary analysis has suggested that within pedigrees in which the mother has RA, the features of genetic anticipation and observations consistent with premutation models may prevail.

Adolescent

Molecular evidence for non-penetrance in Best's disease.

The present study provides evidence for a possible case of non-penetrance in Best's disease. We have analysed the at risk members of a three generation family with an established history of Best's disease by ophthalmoscopic examination, electrophysiological tests, and genetic analysis. The clinical examination identified 10 affected and five unaffected persons in this family. Genetic linkage analysis strongly supports linkage of the disease locus to DNA microsatellite markers from proximal 11q. The genotyping data were used to construct the familial haplotype associated with Best's disease. One person was identified who has inherited the Best's disease haplotype from his affected mother. Fundus examination and electrophysiological tests have repeatedly been performed in this patient but failed to show any signs of the disease. Based on these findings we have jointly estimated the most likely order of the Best's disease locus relative to the closet flanking markers at various penetrance values. A maximum likelihood estimate for the heterozygote penetrance was reached for the locus order D11S903-Best's disease-PYGM at a penetrance value of 0.96.

Adult

Enhanced glucose oxidation in exercise-induced myocardial ischemia.

BACKGROUND: In animal models, dichloroacetate (DCA) facilitates recovery from severe myocardial ischemia by stimulating glucose oxidation. OBJECTIVE: To evaluate the acute efficacy of DCA as a metabolic anti-ischemic intervention in patients with coronary artery disease (CAD) and exercise-induced myocardial ischemia in a clinical trial. METHODS: Double-blind, randomized, crossover comparison of single dose (50 mg/kg intravenously) DCA versus placebo on clinical and electrocardiographic variables in seven patients with single vessel CAD and 34 patients with multiple vessel CAD during standard dynamic exercise testing. RESULTS: Blood pressure did not differ with placebo or DCA but mean heart rate was higher with DCA at rest (62 versus 59, P < 0.004) and at 5 mins of recovery (78 versus 75, P < 0.02). Exercise duration averaged 538 s with DCA and 534 s with placebo (not significant). Chest pain occurred in 14 patients in both tests, clinical ST depression occurred, in 34 placebo tests and 37 DCA tests (not significant). Body surface potential maps (BSPM) of the decrease in the area under the ST curve from rest to peak exercise averaged -5096 microV's with DCA and -5159 microV's with placebo (not significant). BSPM at 1 and 5 mins postexercise also showed no differences in rate of ST integral recovery. CONCLUSIONS: In the transient regional model of human myocardial ischemia induced by dynamic exercise, the acute administration of the pyruvate dehydrogenase agonist DCA was not associated with clinical or electrocardiographic moderation of, nor accelerated recovery from, ischemia. Whether DCA or metabolically similar agents that enhance oxidative metabolism are beneficial in other ischemic settings, such as the no-flow states of acute ST elevation myocardial infarction or angioplasty, requires further systematic evaluation.

Adult

High-resolution meiotic and physical mapping of the best vitelliform macular dystrophy (VMD2) locus to pericentromeric chromosome 11.

Best vitelliform macular dystrophy (VMD2) has previously been linked to several microsatellite markers from chromosome 11. Subsequently, additional genetic studies have refined the Best disease region to a 3.7-cM interval flanked by markers at D11S903 and PYGM. To further narrow the interval containing the Best disease gene and to obtain an estimate of the physical size of the minimal candidate region, we used a combination of high-resolution PCR hybrid mapping and analysis of recombinant Best disease chromosomes. We identified six markers from within the D11S903-PYGM interval that show no recombination with the defective gene in three multigeneration Best disease pedigrees. Our hybrid panel localizes these markers on either side of the centromere on chromosome 11. The closest markers flanking the disease gene are at D11S986 in band p12-11.22 on the short arm and at D11S480 in band q13.2-13.3 on the proximal long arm. This study demonstrates that the physical size of the Best disease region is exceedingly larger than previously estimated from the genetic data, because of the proximity of the defective gene to the centromere of chromosome 11.

Base Sequence

Prediction of school outcomes based on early language production and socioeconomic factors.

Early differences in family SES, child language production, and IQ were related to outcomes in early elementary school in the present prospective, 10-year longitudinal study. In a prior study of family interactional variables associated with language learning, major differences in parenting (i.e., time, attention, and talking) were found to be associated with differences in child productive vocabulary between 7 to 36 months of age, and child IQ, favoring higher-SES parents. Lower-SES children were exposed less often than higher-SES children to diverse vocabulary through their parents' attention and talking, and they were prohibited from talking more often. In the current study, 32 children involved in the earlier study were repeatedly assessed between 5 to 10 years of age, while in kindergarten through third grade. Results indicated that SES-related differences in child language prior to school were predictive of subsequent verbal ability, receptive and spoken language, and academic achievement assessed on standardized tests in kindergarten through grade 3. However, none of the predictor variables were related to direct measures of elementary schooling. When combined with a composite SES indicator, early child language production significantly increased the variance accounted for in the prediction of elementary language and academic competencies in each subsequent year in elementary school. Implications are discussed in terms of the stability of performance on language and academic performance measures of children who entered school with different early language learning experiences, and the need to consider early home- and school-based intervention designed to prevent or ameliorate these trends.

Child

Effects of antiplatelet therapy with indobufen or aspirin-dipyridamole on graft patency one year after coronary artery bypass grafting.

Saphenous vein coronary artery bypass graft patency can be increased by antiplatelet therapy. Aspirin plus dipyridamole are effective but are associated with tolerability problems. Indobufen is a possible alternative antiplatelet agent that may be better tolerated. A prospective, randomized, double-blind, parallel-group study was undertaken to compare the efficacy and safety of indobufen 200 mg twice daily with aspirin 300 mg thrice daily plus dipyridamole 75 mg thrice daily in preventing occlusion of autologous saphenous vein coronary artery bypass grafts. A total of 803 patients were randomized in the study, of whom 552 had a follow-up coronary angiogram approximately 1 year after operation. All anastomoses were patent in 56% of indobufen-treated patients and 59% of aspirin-dipyridamole recipients (p = 0.384). The percentage of all anastomoses patent was 82% in the indobufen group and 83% in the aspirin-dipyridamole group (p = 0.297). Mean postoperative blood loss was significantly less in the indobufen group (p = 0.043). Patients who received indobufen also had significantly fewer adverse events considered to be treatment-related compared with aspirin-dipyridamole recipients (p = 0.02). At the doses tested indobufen was as effective as aspirin plus dipyridamole in preventing occlusion of saphenous vein grafts and was better tolerated. Because indobufen was associated with less postoperative blood loss it may be used before operation in coronary artery bypass grafting.

Adolescent

Ocular clinicopathologic study of the mitochondrial encephalomyopathy overlap syndromes.

Recent advances in molecular genetics have led to a better understanding of mitochondrially inherited diseases. Mitochondrial encephalomyopathy overlap syndrome is one such group of diseases in which ocular abnormalities are frequently manifest. The authors describe the clinical, molecular genetic, and pathologic findings of two patients with the mitochondrial encephalomyopathy overlap syndrome. The patients shared a similar clinical course with features overlapping the three traditionally distinct clinical phenotypes (the Kearns-Sayre syndrome; the syndrome of mitochondrial encephalopathy, lactic acidosis, and stroke [MELAS], and the syndrome of myoclonus, epilepsy, and ragged red fibers [MERRF]). The patients had identical mitochondrial DNA mutations (at nucleotide position 3243) and had similar ultrastructural abnormalities, including abundant enlarged mitochondria with "whorled" and "tubular" cristae. These abnormal mitochondria appeared to be preferentially distributed in cells with high metabolic activity (retinal pigment epithelium, corneal endothelium, and extraocular muscles).

Abnormalities, Multiple

Linkage studies of HLA and primary Sjögren's syndrome in multicase families.

OBJECTIVE: To define the role of HLA-DR phenotype in the expression of primary Sjögren's syndrome (SS). METHODS: A family study of Caucasian probands with definite primary SS was conducted. Relatives with features of primary SS were classified according to the Fox criteria. Several types of linkage analysis between primary SS and HLA haplotype (HLA-A, B, and DR) were performed. RESULTS: A trend toward haplotype sharing between affected siblings was evident for definite/probable primary SS when analyzed by the Green and Woodrow method. This reached statistical significance when data from other published family studies were included. LOD scores and analyses using the Penrose method showed little evidence of linkage. CONCLUSION: In view of the strong association with HLA-DR3, these results suggest that the HLA-DR3 allele is an important susceptibility factor for expression of primary SS in Caucasians. The apparent haplotype sharing may be a consequence of this association. The potential influence of other genetic factors (major histocompatibility complex [MHC] and non-MHC) is discussed.

Adolescent

Cartilage and bone formation in repairing Achilles tendons within diffusion chambers: evidence for tendon-cartilage and cartilage-bone conversion in vivo.

Rodent Achilles tendons were subjected to midpoint tenotomy and allowed to recover for various times in situ before the operated tissue was removed, placed into a Millipore diffusion chamber, and inserted intraperitoneally into syngeneic hosts. Diffusion chambers were then removed at weekly intervals, such that the total time after the operation (i.e., time allowed to recover in situ plus time within the diffusion chamber) was up to 8 weeks, and examined histologically. Ectopic cartilage was produced within the diffusion chamber after a total of 4 weeks but only if the first 2 weeks of recovery were in situ. With increasing time, calcified cartilage, osteoid, and bone were also observed. Overall, the evidence suggests that the cartilage forms via a direct conversion from tendon tissue and that the bone may form as a result of differentiative changes of hypertrophic chondrocytes.

Achilles Tendon