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Biomedical subjects

R A Williams

Publications and source records attributed to R A Williams.

At least 37 records · Page 2Linked to original sources

Effects of noradrenergic and serotonergic antidepressants on chronic low back pain intensity.

To understand the relative efficacy of noradrenergic and serotonergic antidepressants as analgesics in chronic back pain without depression, we conducted a randomized, double-blind, placebo-control head-to-head comparison of maprotiline (a norepinephrine reuptake blocker) and paroxetine (a serotonin reuptake blocker) in 103 patients with chronic low back pain. Of these 74 completed the trial; of the 29 who did not complete, 19 were withdrawn because of adverse effects. The intervention consisted of an 8-week course of maprotiline (up to 150 mg daily) or paroxetine (up to 30 mg daily) or an active placebo, diphenhydramine hydrochloride (up to 37.5 mg daily). Patients were excluded for current major depression. Reduction in pain intensity (Descriptor Differential Scale scores) was significantly greater for study completers randomized to maprotiline compared to placebo (P=0.023), and to paroxetine (P=0.013), with a reduction of pain by 45% compared to 27% on placebo and 26% on paroxetine. These results suggest that at standard dosages noradrenergic agents may provide more effective analgesia in back pain than do selective serotonergic reuptake inhibitors.

Adrenergic Uptake Inhibitors↗

Health beliefs and reported symptoms among a sample of incarcerated adolescent females.

PURPOSE: To understand the health care needs (or perceived needs) of incarcerated female adolescents by comparing their rates of physical complaints, health attitudes, and treatment seeking to a normative sample. METHODS: A sample (n = 138) of incarcerated girls was administered the Somatic Symptom Checklist, the Illness Attitudes Scales, and the Reynolds Adolescent Depression Scale to assess lifetime prevalence of physical symptoms, attitudes toward health, treatment-seeking experience, and emotional distress, and allow for comparison with a normative sample. Information regarding length of incarceration, race, and school achievement was obtained from institutional records. RESULTS: A median lifetime prevalence of 12 symptoms for the incarcerated sample differed significantly from the median of six symptoms reported by a normative sample. The symptoms most commonly expressed by the detainees were dizziness, heart pounding, chest pains, and nausea. In both their attitudes toward illness and actual physical complaints, these subjects were more concerned about illness and perceived themselves to be more physically impaired. Self-reported symptoms of depression and illness were positively correlated. Physical complaints were independent of age, race, length of incarceration, or achievement scores. CONCLUSIONS: The frequency and variety of somatic complaints, as well as their relationship to emotional distress, among these incarcerated girls highlight the need for integration of physical and mental health services within juvenile facilities.

Adolescent↗

Discrimination between benign and malignant melanocytic skin lesions by multivariate analysis, quantitative S-100 immunohistochemistry, nuclear morphometry and DNA cytometry.

OBJECTIVE: To determine whether combined quantitative immunohistochemistry of S-100, nuclear morphometry and DNA image cytometry improves discrimination between benign and malignant melanocytic skin lesions (MSLs). STUDY DESIGN: S-100 protein expression was measured in tissue sections of MSLs using an image cytometry system. Localized areas of high S-100 expression were used to identify regions in sequential, facing sections in which morphometric and cytometric features of nuclei, including DNA ploidy, were also measured. RESULTS: Malignant cases had significantly higher S-100 protein staining intensity, larger nuclei and greater DNA content (P < .05). High staining intensity for S-100 protein weakly correlated with variation in size of the mean nuclear area (P = .04) and DNA content (P = .03). Combining the features of nuclear area and DNA integrated optical density in areas of high-intensity staining for S-100 protein discriminated more accurately between 12 benign and 16 malignant areas than any of the features along (P = .0003). CONCLUSION: Combined multivariate quantitative immunohistochemical, morphometric and DNA cytometric analysis greatly improves discrimination between benign MSLs and malignant melanoma. Larger test sets are required to confirm the promising results of this initial study.

Cell Nucleus↗

Influence of section thickness, mean nuclear diameter and nuclear crowding on DNA ploidy in histologic sections of melanocytic skin lesions.

OBJECTIVE: To determine the influence of section thickness, nuclear diameter (MND) and area percentage of nuclei (a measure of nuclear crowding) on histologic DNA ploidy assessed by image cytometry (ICM) of primary melanocytic skin neoplasms (MSNs). STUDY DESIGN: Initially a feasibility study was performed to determine if comparable DNA ploidy histograms could be obtained from cell disaggregates and tissue sections. Following this, DNA ICM was performed on Feulgen-stained tissue sections (4, 6, 8 and 10 microns thick) from 30 primary MSNs (20 benign, 10 malignant) with nuclear diameters from 5.6 to 8.6 microns. Area percentage of nuclei was assessed in all cases at all section thicknesses. RESULTS: The feasibility study produced comparable results for cytocentrifuge and tissue section preparations. For sectioned MSNs, DNA ploidy histograms from 4-micron sections had a higher coefficient of variation of the 2c peak than those from 6-, 8- and 10-micron sections. Ten-micrometer sections had marked overlapping of nuclei, and only small numbers of cells could be measured, giving inadequate results. MND and area percentage of nuclei did not have an important influence on the results. CONCLUSION: Adequate DNA ploidy profiles can be obtained by DNA ICM on 6- and 8-micron-thick histologic sections of MSNs, provided that a strict measurement protocol is followed.

Cell Count↗

DNA ploidy and nuclear morphometry for the classification of dysplastic nevi.

OBJECTIVE: To examine the diagnostic value of DNA ploidy and nuclear morphometric features in sporadic dysplastic nevi as compared to those in compound nevi and melanoma. STUDY DESIGN: DNA ploidy profiles plus seven direct and three derived nuclear features were obtained in a series of 120 melanocytic skin neoplasms (30 dysplastic nevi [DN], 30 melanomas [MM], 60 compound nevi [CN]) and the results compared. RESULTS: DNA ploidy separated melanomas from benign melanocytic skin neoplasms with 96.5% accuracy in classifying the grouped cases. The derived nuclear shape factor Form PE and nuclear axis ratio were the most successful discriminants separating DN from MM but allowed only 73.3% correct classification of cases. Separation of DN from CN was best achieved using Form PE and mean nuclear area (74.4% correctly classified). Results from compound nevi in subjects < 25 years of age fell between those for DN and MM. CONCLUSION: Quantitative nuclear cytologic characteristics in sporadic dysplastic nevi span a range seen in common nevi through to those in thin melanomas. Cytologic changes in sporadic dysplastic nevi overlap those seen in other melanocytic skin neoplasms. Therefore, other reproducible morphometric features need to be assessed in order to further refine the histopathologic diagnosis of this entity.

Adult↗

Depression in the workplace. Impact on employees.

Given the current high incidence of depression, occupational health nurses in all work settings are likely to encounter many employees who suffer from some form of depression. Depression has the highest medical benefit costs for all behavioral conditions and results in more days of disability than chronic medical conditions such as heart disease, hypertension, diabetes, and lower back pain. Advances in understanding the physiologic changes in the brain which cause depression have lead to development of effective psychopharmacologic agents for treatment. Depressed individuals have the most positive responses with a combination of medication and psychotherapy. Nurses need to assist affected employees to obtain optimal mental health care so they may remain as functional as possible, thereby diminishing the detrimental effects of the illness.

Antidepressive Agents↗

Cloning and thermostability of TaqI endonuclease isoschizomers from Thermus species SM32 and Thermus filiformis Tok6A1.

Two TaqI endonuclease (hereafter referred to as TaqI) isoschizomer genes, tsp32IR from Thermus species SM32 of Azores and tfiTok6A1I from T. filiformis Tok6A1 of New Zealand, were cloned in Escherichia coli. The overexpressed enzymes were partly purified and their thermostability was determined. In the medium-salt buffer, Tsp32IR, TfiTok6A1I and one previously cloned TaqI isoschizomer (TthHB8I) were more thermostable than TaqI. Tsp32IR remained partly active up to 90 degreesC in the low-salt buffer. Six amino acid residues that are identical in the three high thermostability isoschizomers (Tsp32IR, TfiTok6A1I and TthHB8I) but differ in TaqI might provide added rigidity for thermostabilization. These include four proline residues located in or near loop regions, and one alanine and one arginine located at helix regions in the predicted TaqI endonuclease secondary structure. The possible role of these residues in thermostabilization was evaluated by mutagenizing the TaqI enzyme. Mutants generated at these six positions were less thermostable than wild-type TaqI. The results suggest that the surrounding sequence or structural context might be as important as the mutation itself.

Amino Acid Sequence↗

BstB7SI (R decreases CCGGY), a thermostable isoschizomer of Cfr10I, from a strain of Bacillus stearothermophilus isolated from oil-contaminated soil in Kuwait.

Isolates of thermophilic bacteria from desert soil in Kuwait, heavily contaminated with crude oil, have been screened for the presence of restriction endonuclease activity. One of the isolates (B7S), identified as Bacillus stearothermophilus, showed a high level of restriction endonuclease activity when a cell-free extract was incubated with lambda bacteriophage DNA at 65 degrees C. A type II restriction endonuclease (BstB7SI) has been partially purified from this isolate. BstB7SI recognises the six-base sequence RCCGGY (R = A or G; Y = T or C) and hydrolyses the phosphodiester bond in both strands of the DNA substrate between the first and second bases of the recognition sequence 5'-R decreases CCGGY-3'producing four-base 5' overhangs. BstB7SI is therefore an isoschizomer of the mesophilic prototype restriction endonuclease Cfr10I. BstB7SI has a pH optimum of 9.7, requires 10 mM MgCl2 and 75 mM NaCl for maximum activity, and retains full enzyme activity when incubated for 5 min at temperatures up to 70 degrees C.

Base Sequence↗

The psychosocial impact of macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD), the leading cause of irreversible blindness and low vision among the elderly, has not been well studied with regard to its impact on daily life. This study was designed to demonstrate the impact of AMD on quality of life, emotional distress, and functional level. PARTICIPANTS: The study sample consisted of 86 elderly adults (average age, 79 years) with AMD who were legally blind in at least 1 eye. Participants completed a battery of measures that included the Quality of Well-being Scale, the Instrumental Activities of Daily Living index, self-rated general health status, and the Profile of Mood States. RESULTS: Persons with AMD experienced significant reductions in key aspects of daily life. Their ratings for quality of life (average Quality of Well-being Scale score=0.581) and emotional distress (average Profile of Mood States total score=65.36) were significantly worse than those for similarly aged community adults and were comparable with those reported by people with chronic illnesses (eg, arthritis, chronic obstructive pulmonary disease, acquired immunodeficiency syndrome, and bone marrow transplants). Patients with AMD were also more likely than a national sample of elderly individuals to need help with daily activities. Visual acuity was related to ability to carry out daily activities (Instrumental Activities of Daily Living, r=0.28, P=.008). Quality of life ratings were significantly related to the ability to carry out daily activities (r=-0.38, P=.001), self-rated general health status (r=-0.21, P=.05), and emotional distress (Profile of Mood States total score, r=-0.25, P=.02). Individuals with a shorter period of perceived vision loss were more likely to report high levels of emotional distress (r=-0.24, P=.03) than those with a longer period of perceived vision loss. Further, those who were blind in 1 eye were even more significantly distressed than those who were blind in both eyes. CONCLUSIONS: Elderly persons with AMD causing legal blindness in 1 or both eyes have significant emotional distress and profoundly reduced quality of life and need help with key daily activities.

Activities of Daily Living↗

Effect of surgical panel composition on patient outcome at a level I trauma center.

OBJECTIVE: To compare the effect of staffing with general surgeons vs trauma specialists on patient outcome at a trauma center. DESIGN: The care of injured patients at a level I urban trauma center serving a population of 2.5 million was the responsibility of 12 surgeons (10 general surgeons and 2 trauma specialists) between January 1 and June 30, 1996 (group 1). Between July 1 and December 31, 1996 (group 2), trauma was the responsibility solely of 4 trauma specialists. An additional comparison was made with those patients in group 1 who were admitted to the general surgeons (group 1A). The outcomes and quality of care for these periods, as determined by the quality assurance screens, were retrospectively analyzed and compared. SETTING: Urban, tertiary care, level I trauma center. PARTICIPANTS: Each trauma and burn patient admitted during the study periods is included in this study. Upon the patient's discharge from the hospital, specially trained nurses completed a review of the patient's stay and entered it into the TraumaOne database (Lancet Technology Inc, Cambridge, Mass). There were 693 trauma patients in group 1 (472 in group 1A) and 734 patients in group 2. MAIN OUTCOME MEASURES: Mortality, length of stay, and 16 quality assurance screens were quantified and compared using chi(2) analyses and t tests. RESULTS: The age and sex of the 2 groups were similar. The mortality rate was 6.2% (43/693) in group 1, 6.1% (29/472) in group 1A, and 6.5% (48/734) in group 2 (P = .80 and P = .78, respectively). When stratified by injury severity score (ISS), lengths of stay were statistically similar, except for patients with an ISS of 0 to 7. Patients with an ISS of 0 to 7 in groups 1 and 1A stayed a mean of 2.6 days, compared with 3.2 days for group 2 (P = .01 and P = .02, respectively). The results of quality assurance screens (missed injury, wound infection, readmission, and 13 others) were similar in the 2 groups. CONCLUSIONS: Transitions in staffing afforded the opportunity to examine patient outcomes by surgeon specialization and frequency of call. In our sample, 12 well-trained surgeons taking call less frequently managed a trauma service as efficiently as a group of 4 trauma specialists, without any differences in morbidity and mortality.

Adult↗

The contribution of job satisfaction to the transition from acute to chronic low back pain.

OBJECTIVE: To determine the extent to which job satisfaction predicts pain, psychological distress, and disability 6 months after an initial episode of low back pain (LBP). DESIGN: A longitudinal design was used to follow an inception cohort experiencing first-episode low back pain with assessment at 2 and 6 months after pain onset. SETTING: Urban medical center outpatient orthopedic clinic. PATIENTS: The consecutive sample was comprised of 82 men with initial-onset acute LBP (T6 or below, daily pain for 6 to 10 weeks). INTERVENTION: Usual orthopedic care. MAIN OUTCOME MEASURES: The primary study outcomes were pain (Descriptor Differential Scale, Visual Analog Scales); disability (Sickness Impact Profile, Quality of Well-Being); and psychological distress (Beck Depression Inventory, Hamilton Rating Scale for Depression, Automatic Thoughts Questionnaire); predictor variables were orthopedic impairment (Waddell Physical Impairment Index) and job satisfaction (Job Descriptive Index, Work APGAR). RESULTS: Measures of job satisfaction, pain, disability, and psychological distress at baseline and 6 months after pain onset were separately reduced into factors using principle components factor analysis. In hierarchical multiple regression analyses, baseline job satisfaction significantly predicted variance in outcome scores at 6 months after pain onset, beyond the variance explained by control factors (demographics; baseline pain, mood, and disability; orthopedic impairment). Zero-order correlations between job satisfaction and orthopedic impairment were small and nonsignificant, suggesting that these two variables act independently in predicting outcome. Although type of work performed (desk work or work requiring light, moderate, or heavy lifting) and social position were correlated with job satisfaction at baseline, neither contributed to the prediction of outcome at 6 months. CONCLUSIONS: Satisfaction with one's job may protect against development of chronic pain and disability after acute onset back pain and, alternatively, dissatisfaction may heighten risk of chronicity. Vocational factors should be considered in the rehabilitation of acute back injury.

Acute Disease↗

Progesterone 6-hydroxylation is catalysed by cytochrome P-450 in the moderate thermophile Bacillus thermoglucosidasius strain 12060.

The moderate thermophile, Bacillus thermoglucosidasius, transforms progesterone into four metabolites. These are 6alpha- and 6beta-hydroxyprogesterone, androstenedione and testosterone. This is the first report of bacterial 6alpha-hydroxylation of steroids. The identity of the progesterone metabolites shows that there are three major types of transforming activity in this organism; C-17-C-20 lyase that cleaves the pregnane side chain of the substrate, C-17 oxidoreductase that interconverts the metabolites androstenedione and testosterone, and 6-hydroxylation. 6-hydroxylation activity was purified virtually to homogeneity and was shown to be catalysed by a cytochrome P-450 monooxygenase enzyme. This is the first report of a thermostable cytochrome P-450.

Bacillus↗

Transition to chronic pain in men with low back pain: predictive relationships among pain intensity, disability, and depressive symptoms.

Pain intensity, disability, and depressive symptoms are hallmarks of chronic pain conditions, but little is known about the relationships among these symptoms in the transition from acute to chronic pain. In this study, an inception cohort of men with low back pain (N = 78) was assessed at 2, 6, and 12 months after pain onset. At 6 months, pain intensity, disability, and depressive symptoms were predicted only by their respective levels at 2 months after pain onset. At 12 months, pain intensity and depressive symptoms were predicted by heightened disability at 6 months after pain onset; 12-month depressive symptoms also were predicted by 2-month disability. Pain intensity was not predictive of changes in disability or depressive symptoms. These findings suggest that functional disability plays a more prominent role than pain intensity in the transition from acute to chronic pain. A "failure to adapt" conceptual model is presented to account for these results.

Adolescent↗

Attitudes toward psychiatric medications among incarcerated female adolescents.

OBJECTIVE: Beliefs about and attitudes toward pharmacotherapy have been shown to play an important role in mediating compliance with psychoactive medications. This study is an examination of attitudes toward drug treatment in a sample of delinquent incarcerated girls. METHOD: Female adolescents (N = 214) in a juvenile detention facility were administered a questionnaire assessing general beliefs and specific concerns about taking psychiatric medications. Demographic and historical data, including prior psychiatric drug treatment and illicit substance abuse, were also examined as possible influencing variables. RESULTS: Nearly one half of subjects were skeptical about the benefits of pharmacotherapy. Prior illicit drug use did not influence attitudes, but having been treated with psychiatric medication was related to enhanced perceptions of the efficacy and acceptance of such therapy. Specific concerns about untoward effects of pharmacotherapy were identified. CONCLUSIONS: Results suggest that these delinquent adolescents would benefit from techniques to improve initial attitudes toward treatment and challenge the prescribing physician to consider the unique worries and concerns that may undermine compliance with medication regimens among teenagers.

Adolescent↗

Quasispecies evolution of a hypervariable region of the feline calicivirus capsid gene in cell culture and in persistently infected cats.

Feline calicivirus (FCV) is a respiratory pathogen of cats that is capable of causing persistent infections. This study examined the evolution of a hypervariable region of the FCV capsid gene both during 90 passages in cell culture and during replication in persistently infected cats. This region of the capsid protein is known to contain neutralization epitopes and may be a target for immune evasion during virus persistence in the host. Sequence analysis showed that FCV exists as a quasispecies which evolved both in cell culture and in persistently infected cats. Changes involved both loss of sequence present in the infecting isolate and a gain of both synonymous and non-synonymous nucleotide substitutions to generate sequences not detected within earlier isolates. Overall, these changes led to a reduction in population heterogeneity over time. Where virus populations were highly homogeneous allowing a consensus sequence to be determined, evolution rates for the consensus sequence ranged from 0.10-1.07 substitutions per nucleotide per year. Marked changes in virus neutralization profiles were seen in isolates obtained sequentially from a persistently infected cat. This was not the case with cell culture passaged virus, suggesting that the individual amino acid changes found only in virus from persistently infected cats may significantly alter the antigenic profile of FCV, and may be the result of immune selection.

Amino Acid Sequence↗

Computed tomography-assisted management of splenic trauma.

BACKGROUND: In patients who have suffered an injury to the spleen, preservation of the organ is of the utmost importance. To assist in management, contrast-enhanced computed tomography (CT) has been used. We reviewed our experience with a protocol for nonoperative management of splenic trauma based on CT grading of the injury. METHODS: During the initial period of the study, 50 CT examinations for blunt abdominal trauma in adults were reviewed by staff radiologists for evidence of splenic injury. The radiologists, blinded to clinical management decisions, graded the CT studies as "A" if there was a subcapsular hematoma or capsular disruption, "B" if there was a parenchymal injury not extending into the hilum, or "C" if there was deep laceration of fracture of the hilum. Following confirmation of the accuracy and reproducibility of the grading scale, the splenic trauma management protocol was instituted, in which nonhilar injuries were managed nonoperatively. RESULTS: In the initial assessment, patients managed nonoperatively had shorter hospital stays and received fewer blood transfusions than those undergoing operation. Among 30 patients subsequently enrolled in the protocol, those treated nonoperatively remained in the hospital for fewer days than those treated surgically. Again, fewer units of blood and platelets were used in the nonoperative group. Institution of the protocol decreased the incidence of celiotomy. CONCLUSIONS: The severity of splenic trauma evident on CT staging guides safe nonoperative management. Patients not suffering injury to the splenic hilum (A and B scores) can be managed without operation, resulting in shorter hospital stays and fewer blood products used.

Abdominal Injuries↗