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Biomedical subjects

D Walker

Publications and source records attributed to D Walker.

At least 271 records · Page 15Linked to original sources
PubMed1992

Skeletal muscle metabolism in the chronic fatigue syndrome. In vivo assessment by 31P nuclear magnetic resonance spectroscopy.

BACKGROUND: Previous study of patients with chronic fatigue syndrome (CFS) has demonstrated a markedly reduced dynamic exercise capacity, not limited by cardiac performance and in the absence of clinical neuromuscular dysfunction, suggesting the possibility of a subclinical defect of skeletal muscle. METHODS: The in vivo metabolism of the gastrocnemius muscles of 22 CFS patients and 21 normal control subjects was compared during rest, graded dynamic exercise to exhaustion and recovery, using 31P nuclear magnetic resonance (NMR) spectroscopy to reflect minute-to-minute intracellular high-energy phosphate metabolism. RESULTS: Duration of exercise was markedly shorter in the CFS patients (8.1 +/- 2.8 min) compared with the normal subjects (11.3 +/- 4.3 min) (p = 0.005). There were large changes in phosphocreatine (PCr), inorganic phosphate (Pi), and pH from rest to clinical fatigue in all subjects, reflecting the high intensity of the exercise. The temporal metabolic patterns were qualitatively similar in the CFS patients and normal subjects. There were early and continuous changes in PCr and Pi that peaked at the point of fatigue and rapidly reversed after exercise. In contrast, pH was relatively static in early exercise, not declining noticeably until 50 percent of total exercise duration was achieved, and reaching a nadir at 2 min postexercise, before rapidly reversing. There were no differences in pH at rest (7.08 +/- 0.04 vs 7.10 +/- 0.04), exhaustion (6.85 +/- 0.17 vs 6.76 +/- 0.17) or early (6.64 +/- 0.25 vs 6.56 +/- 0.24) or late recovery (7.09 +/- 0.04 vs 7.10 +/- 0.05), CFS patients vs normal subjects, respectively (NS). Neither were there intergroup differences (NS) in PCr or Pi. Although, quantitatively, the changes in PCr, Pi, and pH were marked and similar in both groups from rest to exhaustion, the changes all occurred much more rapidly in the CFS patients. Moreover, adenosine triphosphate (ATP) was significantly (p = 0.007) less at exhaustion in the CFS group. CONCLUSIONS: Patients with CFS and normal control subjects have similar skeletal muscle metabolic patterns during dynamic exercise and reach similar clinical and metabolic end points. However, CFS patients reach exhaustion much more rapidly than normal subjects, at which point they also have relatively reduced intracellular concentrations of ATP. These data suggest a defect of oxidative metabolism with a resultant acceleration of glycolysis in the working skeletal muscles of CFS patients. This metabolic defect may contribute to the reduced physical endurance of CFS patients. Its etiology is unknown. Whether CFS patients' overwhelming tiredness at rest has a similar metabolic pathophysiology or etiology also remains unknown.

Adenosine Triphosphate↗
PubMed1992

Characterization of chemotherapy mobilized peripheral blood progenitor cells for use in autologous stem cell transplantation.

Twenty patients were treated with chemotherapy to mobilize progenitors into the blood. Peripheral blood stem cells were quantitated in peripheral blood or leukapheresis products using colony assays and flow cytometric measurement of CD34+ cells. In four patients where complete sets of serial samples were obtained, the appearance of CD34+ cells preceded the increase in CFU-GM by 24-48 h. Peak levels of CD34+ cells ranged from 0.6-5% and coincided with the peak increase in CFU-GM. Mobilized CD34+ cells contained subsets expressing CD33, CD13, CD45RA, CD38, HLA-DR, CD61 and CD41. Subsets of CD34+ cells expressing CD33, CD13, or CD45RA represent committed myeloid progenitors. In contrast to bone marrow CD34+ cells, few mobilized CD34+ cells expressed CD71, CD7, CD19 or CD10. Prompt engraftment of granulocytes greater than 500 x 10(6)/l at a median of 13 days and platelets greater than 50 x 10(9)/l at a median of 15 days was observed in patients reconstituted with mobilized cells. These data indicate that CD34+ cells mobilized during recovery from chemotherapy are predominantly myeloid in phenotype and contain few actively proliferating cells or cells with lymphoid phenotypes.

Antigens, CD↗
PubMed1992

In vivo skeletal muscle metabolism during dynamic exercise and recovery: assessment by nuclear magnetic resonance spectroscopy.

BACKGROUND: The purpose of this study was to define temporally phosphorus metabolism and pH in the gastrocnemius muscles of 21 normal adult subjects during rest, dynamic exercise to exhaustion, and early and late recovery. METHODS: In vivo nuclear magnetic resonance spectroscopy. RESULTS: At rest, the ratio of phosphocreatine to the alpha peak of ATP averaged 2.26 +/- 0.25, the inorganic phosphate to ATP ratio averaged 0.31 +/- 0.08 and pH averaged 7.10 +/- 0.04. The phosphorus metabolites exhibited immediate and progressive changes with exercise, reaching their minimum (phosphocreatine, 0.95 +/- 0.41) or maximum (inorganic phosphate, 1.95 +/- 0.75) values at exhaustion, after an average exercise of 11 +/- 4 mins. In contrast, pH changed slowly during early exercise, but fell abruptly thereafter and averaged 6.76 +/- 0.17 at exhaustion. Phosphocreatine and inorganic phosphate began to return rapidly towards preexercise values immediately on cessation of exercise. However, pH declined further in the period immediately following cessation of exercise, reaching a nadir of 6.56 +/- 0.24 an average of 2 mins into recovery. Exercise duration did not correlate highly with any metabolic variable. CONCLUSIONS: The data support the concept that the metabolic physiology underlying physical exhaustion of dynamic exercising muscle is multifactorial. The post exercise drop in pH also suggests that normal subjects have a greater contribution to high energy phosphate production from glycolysis, as opposed to oxidative metabolism, in early recovery.

Acid-Base Equilibrium↗
PubMed1991

Pharmacokinetic and pharmacodynamic effects of UK-68,798, a new potential class III antiarrhythmic drug.

1. The pharmacokinetic and pharmacodynamic properties of UK-68,798, a novel selective potential class III antiarrhythmic agent, were studied in 18 patients with coronary artery disease. Three groups of four patients received intravenous doses of 1.5, 3.0 and 4.5 micrograms kg-1 respectively over 10 min. 2. UK-68,798 caused a mean increase in electrocardiographic QTc interval of 41, 40 and 81 ms, and in uncorrected QT interval of 36, 52 and 83 ms at the three dose levels. There were no significant effects on heart rate, blood pressure, PR interval and QRS duration. UK-68,798 was well tolerated with no significant adverse effects. 3. A dosing regimen using a loading infusion of two thirds of the total dose over 15 min with the remainder given over the following 45 min in six patients produced stable plasma concentrations and lengthening in QTc during the maintenance infusion. 4. There was a linear correlation between plasma concentration and change in QTc. The drug exhibited first-order kinetics with a mean clearance of 4.7 +/- 1.2 ml min-1 kg-1 and a mean terminal plasma half-life of 9.7 h. 5. UK-68,798 warrants further study as a selective potential Class III antiarrhythmic agent.

Adult↗
PubMed1991

Effects of thyroidectomy on development of skeletal muscle in fetal sheep.

The influence of the thyroid gland on the functional and histochemical development of fast- and slow-twitch skeletal muscle of fetal sheep has been studied in euthyroid fetal sheep (n = 6) and athyroid fetuses (n = 4) surgically thyroid-ectomized at 70-75 days of gestation. Two fast-twitch muscles, the medial gastrocnemius and extensor digitorum longus, and the slow-twitch soleus muscle were studied at the fetal age of 140 days gestation. The athyroid fetuses had significantly slower twitch contraction and relaxation times in both the medial gastrocnemius and extensor digitorum longus muscles compared with the euthyroid fetuses. Twitch contraction and relaxation times of the soleus were not different in the two groups. Thyroidectomy resulted in an increase in the proportion of fast (type II) muscle fibers and myosin, as shown histochemically and by gel electrophoresis of heavy-chain myosins. These results indicate that the functional maturation of the fast-twitch muscles of sheep is influenced by the presence of an intact thyroid gland from at least 70 days of gestation. In contrast, the slow-twitch soleus muscle fiber diameter and twitch contraction and relaxation times were not different in the two groups.

Animals↗
PubMed1991

Surgical mandibular advancement in adolescents: postsurgical growth related to stability.

Ten of 12 adolescents treated with surgical mandibular advancement showed postsurgical mandibular growth, as indicated by an increase in the distance from condylion to pogonion. In all cases, the growth was expressed vertically relative to the cranial base, so that the chin did not come forward. None of the patients had significant increments of anterior maxillary growth postsurgically. Several patients had vertical maxillary growth, which was compensated by vertical mandibular growth, so that the anteroposterior position of the chin was maintained. Forward growth of the maxilla is minimal after the peak of the adolescent growth spurt, and results of mandibular advancement surgery can be acceptably stable after that time.

Adolescent↗
PubMed1991

The relationship of loneliness, social isolation, and physical health to dietary adequacy of independently living elderly.

This study evaluated the dietary adequacy of elderly individuals to determine whether factors such as loneliness, social isolation, or physical health were related to nutrient intake. The participants (n = 61) were independently living individuals aged 60 to 94 years recruited through senior citizen centers, residential housing areas, and social agencies in Rutherford County, Tennessee. Three-day food records were used to collect dietary data, and nutrient intakes were compared with the 1989 Recommended Dietary Allowances. Three-day social contact diaries were used to measure frequency of interaction with others. The Physical Health Questionnaire was used to evaluate subjectively the number and severity of disease states, and the loneliness index was computed using the revised UCLA Loneliness Scale. Energy and calcium were most likely to be underconsumed, and poor physical health was related to decreased intakes of vitamin A and ascorbic acid. Loneliness was related to dietary inadequacies. We recommend emphasis on education and services to provide home-delivered meals and groceries as well as affordable convenience foods of high nutrient density to enable older individuals to achieve adequate nutrient intake while maintaining an independent life-style.

Black or African American↗
PubMed1990

A comparison of the relative sensitivity of two types of Heaf gun.

A total of 696 secondary school children were given a Heaf test in one forearm with a magnetic head Heaf gun and in the other forearm with a fixed head gun. One week later the results were read blind. In 333 (48%) children the fixed head gun gave a more strongly positive result than the magnetic head gun, while in only 27 (4%) children did the magnetic head gun gives a more strongly positive result. These findings are statistically highly significant (p less than 0.001).

Adolescent↗
PubMed1990

No effect of prostaglandin synthesis inhibition on muscle reflexes in fetal lambs.

The effects of inhibiting prostaglandin (PG) synthesis on fetal breathing movements and on the amplitude of reflex contraction of the digastric muscle (five trials) or hindlimb semitendinosus muscle (seven trials) has been studied in six fetal lambs at 123-139 days gestation. Infusion of either indomethacin (100 mg) or acetaminophen (300 mg) in 30 ml saline over 30 min resulted in an increase in the amplitude and incidence of breathing movements for 3-18 h in the different trials, but there was no change in the mean amplitude of either reflex or in the normal variation of reflex amplitude with changes in electrocortical activity. It is concluded that PGs modulate fetal breathing movements by an action on the brain stem chemoreceptors but do not alter the excitability of neural pathways subserving some cranial and spinal reflexes.

Acetaminophen↗
PubMed1990

Pertussis immunisation: professional attitudes and knowledge.

A survey in Fife found that 98 per cent of health professionals were committed to the prevention of whooping cough. Ninety seven per cent considered pertussis vaccine to be relatively safe and 98 per cent found the current immunisation guidelines satisfactory. However the survey also identified considerable misinterpretation of vaccine contra-indications which would result in many eligible children not being immunised.

Attitude of Health Personnel↗
PubMed1989

Glycosylation of human apolipoprotein E. The carbohydrate attachment site is threonine 194.

The glycosylation of human apolipoprotein (apo) E was examined with purified plasma apoE and apoE produced by transfected cell lines. The carbohydrate attachment site of plasma apoE was localized to a single tryptic peptide (residues 192-206). Sequence analysis and amino sugar analysis of this peptide derived from asialo-, monosialo-, or disialo-apoE indicated that the carbohydrate moiety is attached only to Thr194 in monosialo- and disialo-apoE and that asialo-apoE is not glycosylated. Mammalian cells that normally do not express apoE were transfected with human apoE plasmid expression vectors to test the utilization of potential carbohydrate attachment sites and the role of apoE glycosylation in secretion. Site-specific mutants of apoE, designed to eliminate or alter glycosylation sites, were expressed in HeLa cells by acute transfection. Apolipoprotein E(Thr194----Ala) was secreted exclusively as the asialo isoform, confirming that Thr194 is the site of carbohydrate attachment in these cells and indicating that glycosylation of apoE is not essential for secretion. Apolipoprotein E(Thr194----Asn,Gly196----Ser), which introduces a potential site for N-glycosylation at position 194, was secreted with a higher apparent molecular weight than native, O-glycosylated apoE. Studies with tunicamycin indicated that this apoE was N-glycosylated at Asn194. Stably transfected cell lines expressing human apoE were prepared from wild-type Chinese hamster ovary (CHO) cells and from CHO ldlD cells, which are defective in glycosylation. The transfected wild-type cells secreted multiply sialylated apoE. The transfected ldlD cells also secreted high levels of apoE even in the absence of glycosylation, which confirms that glycosylation is not essential for secretion of apoE.

Animals↗