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Biomedical subjects

K D Williams

Publications and source records attributed to K D Williams.

At least 19 recordsLinked to original sources

Skin surface cooling improves orthostatic tolerance in normothermic individuals.

Previous studies suggest that skin surface cooling (SSC) preserves orthostatic tolerance; however, this hypothesis has not been experimentally tested. Thus the purpose of this project was to identify whether SSC improves orthostatic tolerance in otherwise normothermic individuals. Eight subjects underwent two presyncope limited graded lower-body negative pressure (LBNP) tolerance tests. On different days, and randomly assigned, LBNP tolerance was assessed under control conditions and during SSC (perfused 16 degrees C water through tube-lined suit worn by each subject). Orthostatic tolerance was significantly elevated in each individual due to SSC, as evidenced by a significant increase in a standardized cumulative stress index (normothermia 564 +/- 58 mmHg.min; SSC 752 +/- 58 mmHg.min; P < 0.05). At most levels of LBNP, blood pressure during the SSC tolerance test was significantly greater than during the control test. Furthermore, the reduction in cerebral blood flow velocity was attenuated during some of the early stages of LBNP for the SSC trial. Plasma norepinephrine concentrations were significantly higher during LBNP with SSC, suggesting that SSC may improve orthostatic tolerance through increased sympathetic activity. These data demonstrate that SSC is effective in improving orthostatic tolerance in otherwise normothermic individuals.

Adaptation, Physiological↗

Correlation of early lymphocyte recovery and progression-free survival after autologous stem-cell transplant in patients with Hodgkin's and non-Hodgkin's Lymphoma.

The importance of the association between early lymphocyte recovery and outcome has not been well studied in autologous stem cell transplantation (ASCT). In this retrospective study, we analyzed 90 consecutive patients with non-Hodgkin's and Hodgkin's lymphoma who underwent ASCT. Patients were divided into two groups: group 1 with absolute lymphocyte count (ALC) on day +15 below the median of 667/mm(3), and group 2 with ALC >or=667/mm(3). The median progression-free survival (PFS), but not overall survival (OS), was significantly longer in group 2 when compared to group 1 (16 months vs not reached P=0.02). Group 2 patients also had significantly shorter hospital stay, received higher CD34(+) cell dose, and had shorter time to neutrophil recovery. Multivariate analysis demonstrated day +15 ALC to be an independent prognostic indicator for PFS, but not OS, while CD34(+) cell dose and the number of pretransplant treatments were better predictors for both PFS and OS. We conclude that higher day +15 ALC may independently predict better PFS after ASCT for lymphoma patients; however, whether this merely reflects faster overall recovery caused by higher infused CD34(+) cell dose and less pretransplant therapy needs further investigation.

Adolescent↗

Poor mobilization of peripheral blood stem cells is a risk factor for worse outcome in lymphoma patients undergoing autologous stem cell transplantation.

The effect of poor blood stem cells mobilization on the outcome of autologous stem cell transplantation (ASCT) has not been well studied. Our aim is to evaluate poor mobilization as a prognostic factor in lymphoma patients undergoing ASCT. We analyzed 90 consecutive patients with Hodgkin's (HD) and non-Hodgkin's lymphoma (NHL) who underwent ASCT. Poor mobilization was defined as the inability to obtain > or = 1 x 10(6) CD34+ cells/kg ideal body weight with two large volume aphereses. Patients were divided into 2 groups: group 1 = poor mobilizers, and group 2 = good mobilizers. The poor mobilizers received lower median transplant CD34+ cell dose (2 x 10(6) vs. 4.5 x 10(6)/kg for good mobilizers, P = 0.001), were more heavily pretreated (P = 0.01), and required higher number of aphereses for PBSC collection (P = 0.0006). The median progression-free survival (PFS) in groups 1 and 2 was 10 and 41 months (P = 0.04), while the median overall survival (OS) was 38 months and not reached (P = 0.02), respectively. Univariate analysis showed that > or = 3 pre-transplant treatments, CD34+ cell dose < or = 2 x 10(6), elevated LDH before transplant, and poor mobilization were significant prognostic factors for poor PFS, while only the first three were significant for worse OS. Multivariate analysis using these same four factors revealed that number of pre-transplant treatments (HR = 6.03, P = 0.001), CD34+ cell dose (HR = 0.1, P = 0.0007) were the only independent predictive factors for worse overall outcome. In conclusion, our data show that poor mobilization could indicate poor outcome in lymphoma patients undergoing ASCT, however, it is more likely to be a reflection of the heavy pre-transplant therapy and lower CD34+ cell dose re-infused in this group of patients.

Adolescent↗

The role of interpersonal stress in overeating among high and low disinhibitors.

This study was concerned with the role of interpersonal stress in precipitating eating for high and low disinhibitors. Two forms of stress, ostracism and argument, were compared. A second comparison focused on targets and sources of both forms of interpersonal stress. Fifty-seven females who differed in their level of disinhibition participated in a two-stage experiment. In the first stage, they were engaged in a social interaction with two other people. The second stage involved a taste test; the dependent variable was the amount of food eaten. There were no differences between the ostracism and argument conditions for the amount of food eaten; nor did high and low disinhibitors differ. There was, however, a significant interaction between level of disinhibition and role (target vs. source) for the amount of food eaten. High disinhibitors ate markedly more than low disinhibitors when they were targets; the two groups ate similar amounts when they were sources. Strategies that dieters can employ in order to overcome the tendency to overeat are outlined.

Journal Article↗

The white coat.

Explore the source record for details and available documents.

Humans↗

Cyberostracism: effects of being ignored over the Internet.

Ostracism is such a widely used and powerful tactic that the authors tested whether people would be affected by it even under remote and artificial circumstances. In Study 1, 1,486 participants from 62 countries accessed the authors' on-line experiment on the Internet. They were asked to use mental visualization while playing a virtual tossing game with two others (who were actually computer generated and controlled). Despite the minimal nature of their experience, the more participants were ostracized, the more they reported feeling bad, having less control, and losing a sense of belonging. In Study 2, ostracized participants were more likely to conform on a subsequent task. The results are discussed in terms of supporting K. D. Williams's (1997) need threat theory of ostracism.

Adolescent↗

52-Week oral gavage chronic toxicity study with ubiquinone in rats with a 4-week recovery.

Potential ubiquinone (CoQ10; a natural fermentation product) toxicity was assessed in rats administered CoQ(10) by oral gavage for 1 year at 100, 300, 600, and 1200 mg/(kg day). No adverse changes in mortality, clinical signs, body weight, food consumption, or clinical pathology results occurred. CoQ(10) had elimination half-lives ranging from 10.7 to 15.2 h. At 1200 mg/(kg day), a high incidence of orange, granular, lumenal exudate in nasal turbinates occurred; microscopically, findings similar to those in the turbinates were occasionally observed in small granulomas within lung alveoli. A dose-related increased incidence of vacuolated macrophages (mesenteric lymph nodes) and vacuolated hepatic periportal cells was noted. Neither were associated with tissue damage or organ dysfunction, so they were not considered to be adverse. The nasal turbinate and lung findings were probably secondary to incidental exposure to crystallized test material. Overall, CoQ(10) was well tolerated by male and female rats at dose levels up to 1200 mg/(kg day).

Administration, Oral↗

Preclinical evaluation of single-cell oils that are highly enriched with arachidonic acid and docosahexaenoic acid.

Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important in human brain and retina development, and there is growing evidence showing the importance of these fatty acids in infant nutrition. Triglyceride oils, highly enriched in ARA (ARASCO) and DHA (DHASCO), were evaluated using very high dose acute (20 g/kg) and 4-wk subchronic gavage feedings in weanling Sprague-Dawley rats. The combination of these oils, Formulaid, was also tested in the 4-wk subchronic study, ARASCO, DHASCO and Formulaid were found to have a no-observable-adverse-effect level of more than 2.5 g/ kg/day, 1.25 g/kg/day and 3.75 g/kg/day, respectively. This represents a 50-fold safety margin over the intended use of Formulaid in infant formula. Survival, clinical signs, body weight gain, food consumption, haematology, clinical chemistry and histopathological evaluations failed to show any significant differences in animals administered ARASCO, DHASCO or Formulaid compared with that in control animals administered equal amounts of high oleic sunflower oil. The bioavailability of ARASCO, DHASCO and Formulaid was verified by increases in DHA and ARA levels in heart and liver tissues in these animals. Because these oils are enriched in only a single bioactive fatty acid, and they have been shown to be safe, they may offer a new source of these fatty acids in speciality foods such as infant formula.

Administration, Oral↗

Diapause in Drosophila melanogaster females: a genetic analysis.

Female Drosophila melanogaster exhibit ovarian diapause at low temperatures and short day lengths. We found that D. melanogaster isofemale lines from Windsor (Ontario, Canada) had a significantly higher percentage of females in diapause than did those from Cartersville (Georgia, U.S.A.). To investigate the heredity of this trait, we performed a 16-reciprocal cross analysis using two extreme isofemale lines called W and C. We found that diapause in D. melanogaster is inherited as a simple autosomal recessive trait with the C response (less flies in diapause) completely dominant to the W one. Maternal and cytoplasmic factors did not affect differences in diapause in these lines. The result of our genetic analysis of diapause in D. melanogaster opens may avenues for the genetic dissection of this ecologically relevant trait.

Adaptation, Physiological↗

High dose refractoriness to the neuromuscular toxicity of dithiobiuret in rats.

Increasing the daily dose of dithiobiuret (DTB) given to rats from 0.5 to 1 to 5 mg/kg shortened the latency to onset of treadmill failure and associated flaccid muscle tone from 7 to 5 to 3 days, respectively. Death generally did not follow treadmill failure for at least 2-3 days. After 3 consecutive days of treatment with 5 mg/kg, gastrocnemius muscle contractions elicited by high frequency trains of nerve stimulation were lower in peak tension and more susceptible to tetanic fade (rapid tension decline in tetanus) than were contractions from control rats. Conversely, rats given 12 mg/kg of DTB for 3 days did not exhibit treadmill failure, flaccid skeletal muscle tone, or tetanic contractile abnormalities. Additional treatment with this dose for 2-3 days was required to produce treadmill failure which was not accompanied by flaccid muscle tone. Refractoriness to development of toxicity with DTB was limited in its spectrum; decreased feed and water intake, weight loss, diuresis, dehydration, chromodacryorrhea, and production of mucoid feces occurred even in the absence of flaccid muscle tone. Tissue distribution of DTB-derived [14C] determined 3 hr after injection of [14C]-DTB (12 mg/kg) was largely unaffected by prior treatment with unlabeled DTB (12 mg/kg/day x 2 days). Conventional microelectrode recording studies using end-plates of extensor digitorum longus muscles indicated that abnormalities occurred in quantal release of acetylcholine (ACh) after 5mg/kg/day but not 12 mg/kg/day of DTB. Specifically, reduced quantal content, increased amplitude and prolonged decay of miniature end-plate potentials were observed. The mechanism by which large daily doses overcome or prevent the expected development of flaccid muscle tone and depressed release of ACh typically associated with treatment with DTB does not involve compensatory increases in quantal release of ACh, or altered distribution of the compound.

Animals↗

Iselin's disease.

Iselin's disease (traction apophysitis of the tuberosity of the fifth metatarsal) has been reported rarely, but is probably more common than appreciated. It appears to be more common in athletically active older children and adolescents. Four patients with this condition were treated conservatively and all had resolution or improvement of symptoms. In one, however, nonunion developed and continues to cause intermittent pain at age 20 years. Early recognition and treatment may prevent long-term complications.

Adolescent↗

Social loafing and social compensation: the effects of expectations of co-worker performance.

Previous research has suggested that people tend to engage in social loafing when working collectively. The present research tested the social compensation hypothesis, which states that people will work harder collectively than individually when they expect their co-workers to perform poorly on a meaningful task. In 3 experiments, participants worked either collectively or coactively on an idea generation task. Expectations of co-worker performance were either inferred from participants' interpersonal trust scores (Experiment 1) or were directly manipulated by a confederate coworker's statement of either his intended effort (Experiment 2) or his ability at the task (Experiment 3). All 3 studies supported the social compensation hypothesis. Additionally, Experiment 3 supported the hypothesis that participants would not socially compensate for a poorly performing co-worker when working on a task that was low in meaningfulness.

Adult↗

Changes in acetylcholine receptor distribution and binding properties at the neuromuscular junction during aging.

Junctional and extrajunctional acetylcholine receptors were characterized in diaphragm muscle obtained from mature adult and aged rats. Rhodamine-conjugated alpha-bungarotoxin was used to visualize receptor localization. At this level of resolution, there were no major changes in receptor distribution, and nerve terminals were consistently associated with receptors and vice versa. Specific binding characteristics were assayed by measuring 125I-alpha-bungarotoxin binding. Maximal binding to intact junctional and extrajunctional tissue samples was greater in the older rats. The association rate constant in minced tissue decreased in the older animals. Retardation of the initial rate of toxin binding by d-tubocurarine was described by a two-component nonlinear Hofstee plot; values of Ki were about the same for both age groups, but there was a significant shift towards the low-affinity values in the aged rats. Miniature end-plate currents (m.e.p.c.s.) were recorded under voltage-clamp conditions before and after AChE inhibition. When AChE activity was inhibited m.e.p.c. amplitudes and decay time-constants increased in both age groups. The magnitude of these increases was larger in the older animals. Inhibition of AChE did not affect mean channel open time, which was estimated from spectral analyses of ACH-induced membrane noise. Lipid composition was assayed in whole muscle and isolated sarcolemma. Muscle cholesterol concentration rose 15-20 percent, but phospholipid concentrations were maintained. However, neither cholesterol, phospholipid levels, nor membrane fluidity changed significantly with age in isolated sarcolemmal membrane fractions. These data indicate that the numbers of junctional and extrajunctional receptors increase with age. In the junctional region, this is quite likely due to an expanded field of receptors and not an increased density. This is associated with an increased fraction of receptors with lower binding affinity during aging. These changes apparently are not caused by major changes in membrane fluidity or lipid composition.

Aging↗

Synovial cysts of the lumbosacral spine: diagnosis by MR imaging.

Intraspinal synovial or ganglion cysts are uncommon lesions associated with degenerative lumbosacral spine disease. CT usually reveals cystic lesions adjacent to a facet joint, and they may show calcification. MR imaging of four surgically confirmed cases of intraspinal synovial cysts revealed subtle signal changes compared with CSF. Short TR/TE images showed the lesions to be slightly hyperintense in three cases and isointense in one case. Long TR/TE sequences revealed a hyperintense appearance in two cases and a hypointense appearance in the others. A peripheral rim of decreased signal on long TR/TE images probably reflects fine calcification or hemorrhage in the margins of the cysts. The multiplanar and contrast characteristics of MR make this technique well suited to the diagnosis of herniated disk, degenerative facet disease, and synovial cyst.

Aged↗

Cholesterol conservation in skeletal muscle associated with age- and denervation-related atrophy.

The lipid composition of muscles with age- and denervation-atrophy was assayed in whole muscle and isolated sarcolemma of rats aged 10 and 25 months. Although muscle mass decreased at least 17% during aging, muscle cholesterol concentration rose 15-20%. However, phospholipid concentrations were maintained; therefore, the cholesterol-to-phospholipid ratio increased during aging. Plasma cholesterol levels also rose 35%, but this could account for only about 10% of the age-related difference in muscle cholesterol. Likewise, following denervation (7 days) muscle mass decreased by at least 30%, but muscle cholesterol-to-phospholipid ratio increased; the magnitude of the denervation-induced response was unaffected by aging. To localize the source of cholesterol deposition during aging, these assays were repeated on isolated sarcolemma, sarcoplasmic reticulum, and mitochondria membrane fractions. Neither cholesterol nor phospholipid levels changed significantly with age in any of these major membrane systems. Furthermore, sarcolemmal fluidity, which depends on cholesterol content, did not vary significantly with age. At this level of resolution, it thus appears that skeletal muscle membrane phospholipid composition and fluidity do not change appreciably with age. Elevated cholesterol-to-phospholipid ratios detected in whole muscle may be due to cholesterol deposition in non-myofiber locations.

Aging↗

MR angiography with two-dimensional acquisition and three-dimensional display. Work in progress.

Magnetic resonance arteriograms of healthy volunteers and selected patients were produced with a new spoiled gradient-echo pulse sequence based on time-of-flight phenomena. The procedure involves sequential acquisition of many contiguous, thin (1.5-mm) axial two-dimensional sections. These volume data are then submitted to a raytracing projection program, which retrospectively yields multiple arbitrary projection angles rotating through any plane. Venous structures are suppressed with a presaturation slab superior to the current section. The slab location is advanced in concert with advancement of each new section location. The acquisition time varies from 6 to 13 minutes, depending on the number of sections acquired for three-dimensional display. This method obviates the subtraction of image data sets to suppress signals from stationary spins, is more sensitive to slow blood flow than three-dimensional methods of acquisition, and shows special promise for the study of extracranial vascular disease.

Adult↗

Temporal analysis of dithiobiuret neurotoxicity in rats and assessment of potential nonneural causes.

To evaluate the hypothesis that depressed neuromuscular transmission causes dithiobiuret (DTB)-induced muscle weakness in rats, the temporal development of impaired treadmill performance and deficits in the nerve-elicited muscle contractions were compared during daily treatment with the toxicant (DTB, 1 mg/kg/day X 6 days). Diminished treadmill test performance after 4 days of treatment marked the initial detection of impaired motor function. At this time fading (loss of tension during tetanus) of gastrocnemius contractions elicited in response to 100-Hz sciatic nerve stimulation occurred in DTB-treated rats but not in controls. After 5 and 6 days of treatment, treadmill failure became complete, tetanic fade worsened dramatically, and peak contractile tension measured during trains of nerve stimulation (10-250 Hz) decreased progressively. Appearing by Day 6 were marked body weight loss, dehydration, hypothermia, and a depression in serum concentrations of thyroid hormones. Total oxygen content of the blood was not reduced at any time during treatment, and serum concentrations of glucose, sodium, potassium, calcium, chloride, and phosphorus in DTB-treated rats on Day 6 were similar to those of control animals. Therefore, hypoxia, hypoglycemia, or a serum electrolyte imbalance do not initiate or modulate the neuromuscular toxicity. Light microscopic evaluation of liver, kidney, lung, thyroid, and other organs in intoxicated rats was unremarkable and in skeletal muscles and selected sites of brain, spinal cord, and sciatic nerve no morphologically significant lesions were observed. Even when DTB-intoxicated rats were maintained in a state of flaccid muscle weakness for 5 continuous days, peripheral nerve lesions proximal to the intramuscular nerves were not detected. Thus, depressed neuromuscular transmission appears to be the primary cause of the flaccid muscle weakness and no evidence was obtained that nonneural effects of DTB initiate or modulate this effect.

Animals↗