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Biomedical subjects

W Jones

Publications and source records attributed to W Jones.

At least 37 records · Page 2Linked to original sources
PubMed2000

A collaborative approach to developing nursing skills to meet service needs.

Academics, educators and health service managers came together to explore, within their local area, the nature of the perceptions of beginning registered nurses (BRNs) and Nursing Unit Managers (NUMs) to the skills utilised by BRNs within the first six months of practice. A group of 71 BRNs and nine NUMs participated in a cross-sectional survey. BRNs were also asked to rate their preparedness in each particular skill, dependent on the method of teaching--theory/lectures, nursing laboratories and clinical experience. Some 21 skills, relating to medication/fluid administration and skin and wound care, were perceived by 95 per cent or more of the graduates as being used within the first six months. Similar perceptions existed for NUMs and BRNs for 52.4 per cent of the listed skills. Differences in perceptions have led to academics altering the scope of skills being taught and focusing assessment on critical skills for BRNs, and managers increasing awareness among NUMs as to the source of the differences and developing programs to improve clinical interpretation skills. Improvements in the experience of the BRN are likely to occur when all parties work together to bring about positive change. By Barbara Somerville,

Adult↗
PubMed2000

Clinical and fiscal impact of lansoprazole intolerance in veterans with gastro-oesophageal reflux disease.

BACKGROUND: Omeprazole was replaced by lansoprazole as the only proton pump inhibitor on the Veterans Affairs (VA) formulary in February 1997. We aimed to assess the clinical and fiscal impact of this conversion at two VA hospitals. METHODS: We identified lansoprazole intolerant patients using pharmacy databases. We reviewed medical records to obtain data regarding reasons for lansoprazole intolerance. The costs of the formulary change and the savings to the VA were calculated. RESULTS: A total of 3833 patients required long-term proton pump inhibitor therapy; 2224 (58%) were started on lansoprazole and 1479 (39%) were converted from omeprazole to lansoprazole. The remaining 130 (3.4%) patients were never converted from omeprazole to lansoprazole. Of the 3833 patients, 325 (8.5%) currently receive omeprazole therapy; of these, 195 out of 3703 (5.3%) patients are true lansoprazole failures; 172 of these 195 patients completed the study. Most (87%) of the lansoprazole intolerant patients received prior omeprazole. Discontinuation of lansoprazole was due to poor symptom control in 69% and/or side-effects (22%) including diarrhoea (10%), abdominal pain (5%), or hives (1%). The 1-year cost of managing lansoprazole failure in 195 patients was $61 690. However, the savings to the VA during the same time period, which totalled $321 360, more than offset the costs associated with the conversion. CONCLUSIONS: Lansoprazole intolerance requiring omeprazole conversion occurred in 5% of veterans on proton pump inhibitor therapy for chronic gastro-oesophageal reflux disease (GERD) symptoms and in 10% of patients with prior omeprazole success. The VA realized substantial cost savings in association with the formulary change.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Factor XIIa and triacylglycerol rich lipoproteins: responses to exercise intervention.

OBJECTIVES: (a) To determine if factor XIIa (FXIIa) would be sensitive to change from exercise intervention in a group of previously sedentary/low active middle aged men and women; (b) to investigate further the previously reported relation between FXIIa and triacylglycerol (TAG) rich lipoproteins. METHODS: Thirty seven men (mean (SD) age 57 (7) years) and 60 women (mean age 54 (7) years) completed the study. Before the intervention, these subjects were randomly allocated to a group of walkers (n = 81) or controls (n = 16). Before and after an 18 week walking intervention, fasted blood samples were collected and analysed for FXIIa, TAG, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and apolipoprotein (apo) B. RESULTS: Kruskal-Wallis analysis of data obtained before the intervention showed no significant differences (p>0.4) between the walking and control groups for age, height, body mass, gender, FXIIa, TAG, TC, HDL-C, or apo B, although the women did show significantly lower levels of TAG (p<0.04) and higher HDL-C (p<0.0001) than the men. General linear model analysis of data obtained after the intervention, using the baseline value as a covariate, showed significant reductions (p<0.0001) in FXIIa for the walkers compared with the controls. Pearson product-moment correlations also showed significant relations between the concentrations of FXIIa and TAG, TC, LDL-C, and apo B. CONCLUSIONS: The findings of this study suggest that FXIIa is sensitive to change from exercise intervention and support previous research showing an association between the concentrations of FXIIa and TAG rich lipoproteins.

Cholesterol, HDL↗
PubMed2000

I. The neurocognitive profile of Williams Syndrome: a complex pattern of strengths and weaknesses.

The rare, genetically based disorder, Williams syndrome (WMS), produces a constellation of distinctive cognitive, neuroanatomical, and electrophysiological features which we explore through the series of studies reported here. In this paper, we focus primarily on the cognitive characteristics of WMS and begin to forge links among these characteristics, the brain, and the genetic basis of the disorder. The distinctive cognitive profile of individuals with WMS includes relative strengths in language and facial processing and profound impairment in spatial cognition. The cognitive profile of abilities, including what is 'typical' for individuals with WMS is discussed, but we also highlight areas of variability across the group of individuals with WMS that we have studied. Although the overall cognitive abilities (IQs) of individuals with WMS are typically in the mild-to-moderate range of mental retardation, the peaks and valleys within different cognitive domains make this syndrome especially intriguing to study across levels. Understanding the brain basis (and ultimately the genetic basis) for higher cognitive functioning is the goal we have begun to undertake with this line of interdisciplinary research.

Child↗
PubMed2000

II. Hypersociability in Williams Syndrome.

Studies of abnormal populations provide a rare opportunity for examining relationships between cognition, genotype and brain neurobiology, permitting comparisons across these different levels of analysis. In our studies, we investigate individuals with a rare, genetically based disorder called Williams syndrome (WMS) to draw links among these levels. A critical component of such a cross-domain undertaking is the clear delineation of the phenotype of the disorder in question. Of special interest in this paper is a relatively unexplored unusual social phenotype in WMS that includes an overfriendly and engaging personality. Four studies measuring distinct aspects of hypersocial behavior in WMS are presented, each probing specific aspects in WMS infants, toddlers, school age children, and adults. The abnormal profile of excessively social behavior represents an important component of the phenotype that may distinguish WMS from other developmental disorders. Furthermore, the studies show that the profile is observed across a wide range of ages, and emerges consistently across multiple experimental paradigms. These studies of hypersocial behavior in WMS promise to provide the groundwork for crossdisciplinary analyses of gene-brain-behavior relationships.

Adolescent↗
PubMed2000

IV. Neuroanatomy of Williams syndrome: a high-resolution MRI study.

Williams syndrome (WMS), a genetic condition resulting from a contiguous deletion on the long arm of chromosome 7, is associated with a relatively consistent profile of neurocognitive and neurobehavioral features. The distinctiveness and regularity of the profile of learning and behavioral characteristics in this genetic condition suggests that underlying neurobiological correlates may be identifiable. In this initial study, we report findings derived from a high-resolution neuroimaging study of 14 young adult subjects with WMS and an individually matched normal control group. Compared to controls, subjects with WMS were noted to have decreased overall brain and cerebral volumes, relative preservation of cerebellar and superior temporal gyrus (STG) volumes, and disproportionate volume reduction of the brainstem. Analyses also suggested that the pattern of cerebral lobe proportions in WMS may be altered compared to normal controls with a greater ratio of frontal to posterior (parietal+occipital) tissue. Assessment of tissue composition indicated that, relative to controls, individuals with WMS have relative preservation of cerebral gray matter volume and disproportionate reduction in cerebral white matter volume. However, within the cerebral gray matter tissue compartment, the right occipital lobe was noted to have excess volume loss. Combined with our growing knowledge of the function of genes in the commonly deleted region for WMS, more detailed information regarding the structure and function of the WMS brain will provide a unique opportunity for elucidating meaningful correlations amongst genetic, neurobiological, and neurobehavioral factors in humans.

Adult↗
PubMed1999

Environmental study of nylon flocking process.

Environmental measurements for a variety of gas, particulate, and microbiological agents have been made in order to characterize exposures associated with the nylon flocking process. Of all agents measured, particulate is the predominant exposure. Levels of total particulate ranged from O.1 to 240 mg/m3 (x = 11.4 mg/m3). Average respirable particulate was 2.2 mg/m3, ranging from 0.5 to 39.9 mg/m3. Highest levels of particulates were found in the flocking room, and direct reading dust measurements indicate that the highest peak exposures are associated with "blowdown" (a cleaning procedure used between flocking runs). The nature of the airborne particles was investigated using polarized light and scanning electron microscopy. Air samples were found to contain flock particles (fibers nominally 10-15 microm in diameter by about 1000 microm in length) and a variety of respirable particles types, several of which were linked directly to the process. Of special interest were elongated respirable particles, which by microscopic analysis, complemented with melting-point determination, were found to be shreds of nylon.

Air Pollutants, Occupational↗
PubMed1999

Acute inflammatory reaction in rats after intratracheal instillation of material collected from a nylon flocking plant.

Several cases of interstitial lung disease have been diagnosed among workers at a nylon flock plant, but the etiologic agent for the disease outbreak was unknown. The results of a medical survey and industrial hygiene study indicated that the dust present in the plant may be responsible. Thus, airborne dust collected at the plant was examined for its inflammatory potential in rat lungs. The endpoints measured were: (1) breathing rates, (2) differential cell counts of bronchoalveolar lavage cells, (3) alveolar macrophage (AM) chemiluminescence, (4) albumin concentration and matrix metalloprotease activities in the acellular fluid from the initial bronchoalveolar lavage, and (5) pulmonary histopathology. In the first study, rats received a single dose of the airborne dust sample (10 mg/kg body weight) by intratracheal (IT) instillation. At 1 d post-IT, all inflammatory endpoints were significantly increased versus controls, but by 29 d post-IT they did not differ significantly from controls. Histopathology demonstrated mild to moderate, multifocal, suppurative pneumonia, usually centered around bronchioles, at 1 d post-IT. At 29 d post-IT, pulmonary inflammation was minimal to mild and characterized by alveolar histocytosis usually restricted to the immediate area of retained bire-fringent fibers. In subsequent experiments, airborne dust was extracted with water and the dust (washed airborne dust) and water extract (soluble fraction) were separated by centrifugation for further study. Nylon tow dust was prepared in the laboratory by milling uncut nylon strands (called tow) that had not been treated with the finish or dyes that are commonly used in the flock plants. Rats were administered a single dose of a dust sample (10 mg/kg body weight) or the soluble fraction (1.3 ml/kg body weight) by IT administration and the same endpoints were measured at 1 d post-IT. The dust samples caused significant increases in all of the inflammatory endpoints; however, the soluble fraction was much less active. Histological analysis of the lungs 1 d post-IT confirmed lung inflammation was occurring and tended to center around bronchioles. The results suggest that: (1) nylon flocking generates particles of respirable size that can interact with AM in the lung and can be detected in the lung 29 d after exposure, (2) the dust samples examined cause an inflammatory response, (3) water-extractable agent(s) from airborne dust contribute only minimally to the inflammatory response, and (4) the acute inflammatory response to these dusts is substantial when compared to other pathologic occupational dusts previously examined in our laboratory.

Acute Disease↗
PubMed1999

Regulation of the production of soluble IL-4 receptors in murine cutaneous leishmaniasis. The roles of IL-12 and IL-4.

These studies were undertaken with the purpose of elucidating the key signals involved in the regulation of the production of soluble interleukin-4 receptors (sIL-4R) in mice during Th1 and Th2 responses to infection with the parasite Leishmania major. Our results showed that the production of sIL-4R was consistently higher in lymph node cell cultures from animals mounting a predominant Th2 response (BALB/c mice), and that sIL-4R production paralleled that of IL-4 in both mouse strains, even in the presence of a dominant Th1 response (C3H/FeJ mice). Consistently, administration of anti-IL-12 antibodies to infected C3H/ FeJ mice induced a switch from a Th1- to a Th2-type response and resulted in enhanced production of sIL-4R. Addition of rIL-12 to splenic cell cultures, however, was found not to have a direct effect on sIL-4R production induced by IL-4 or T cell mitogens. Moreover, the production of sIL-4R appears to be little influenced by Th1-produced cytokines, inasmuch as recombinant interferon-gamma or supernatants derived from antigen-stimulated Th1 clones did not affect the production of sIL-4R by activated splenic cultures. Despite its correlation with Th2 responses, the presence of IL-4 was not an absolute requirement for the up-regulation of the expression of sIL-4R because increased levels could be induced on cells obtained from IL-4-/- mice. These results indicate that, although enhanced sIL-4R production is a feature related to the activation and/or generation of Th2 responses, it is not absolutely dependent on IL-4 or directly inhibited by IL-12 or Th1 cytokines.

Animals↗
PubMed1999

Structural investigations on human erythrocyte acylpeptide hydrolase by mass spectrometric procedures.

The complete primary structure of human erythrocyte acylpeptide hydrolase has been determined by using a combination of different mass spectrometric procedures and sequencing techniques. These data allowed us to correct the incomplete nucleotide sequence of the DNF15S2 locus on the short arm of human chromosome 3 at region 21, coding for the enzyme. The protein consists of 732 amino acid residues and is acetylated at the N-terminus. Alkylation experiments on the native enzyme demonstrated that all 17 cysteine residues present in the polypeptide chain are in reduced form. Multiple sequence alignment did not reveal striking similarity with proteases of known tertiary structure with the exception of members of the serine oligopeptidase family. Limited proteolysis experiments generated a C-terminal portion, containing all the catalytic triad elements responsible for proteolytic activity, and an N-terminal domain of unknown function, both still strongly associated in a completely active nicked form. The site of tryptic hydrolysis was identified as Arg193. The secondary structural organization of the protease domain of the enzyme is consistent with the alpha/beta hydrolase fold.

Alkylation↗
PubMed1999

Critical role of glass fiber length in TNF-alpha production and transcription factor activation in macrophages.

Recent studies have demonstrated that dielectrophoresis is an efficient method for the separation of fibers according to fiber length. This method allows the investigation of fiber-cell interactions with fiber samples of the same composition but of different lengths. In the present study, we analyzed the effects of length on the interaction between glass fibers and macrophages by focusing on production of the inflammatory cytokine tumor necrosis factor (TNF)-alpha in a mouse macrophage cell line (RAW 264.7). The underlying molecular mechanisms controlling TNF-alpha production were investigated at the gene transcription level. The results show that glass fibers induced TNF-alpha production in macrophages and that this induction was associated with activation of the gene promoter. Activation of the transcription factor nuclear factor (NF)-kappaB was responsible for this induced promoter activity. The inhibition of both TNF-alpha production and NF-kappaB activation by N-acetyl-L-cysteine, an antioxidant, indicates that generation of oxidants may contribute to the induction of this cytokine and activation of this transcription factor by glass fibers. Long fibers (17 micrometer) were significantly more potent than short fibers (7 micrometer) in inducing NF-kappaB activation, the gene promoter activity, and the production of TNF-alpha. This fiber length-dependent difference in the stimulatory potency correlated with the fact that macrophages were able to completely engulf short glass fibers, whereas phagocytosis of long glass fibers was incomplete. These results suggest that fiber length plays a critical role in the potential pathogenicity of glass fibers.

Acetylcysteine↗
PubMed1998

Osteogenic protein-1 (bone morphogenetic protein-7) reduces severity of injury after ischemic acute renal failure in rat.

We have shown that osteogenic protein-1 (OP-1) (bone morphogenetic protein-7) is responsible for the induction of nephrogenic mesenchyme during embryonic kidney development. Gene knock-out studies showed that OP-1 null mutant mice die of renal failure within the first day of postnatal life. In the present study, we evaluated the effect of recombinant human OP-1 for the treatment of acute renal failure after 60 min bilateral renal artery occlusion in rats. Bioavailability studies in normal rats indicate that approximately 1.4 microg OP-1/ml is available in the circulation 1 min after intravenous administration of 250 microg/kg, which then declines steadily with a half life of 30 min. About 0.5% of the administered OP-1 dose/g tissue is targeted for OP-1 receptors in the kidney. We show that OP-1 preserves kidney function, as determined by reduced blood urea nitrogen and serum creatinine, and increased survival rate when administered 10 min before or 1 or 16 h after ischemia, and then at 24-h intervals up to 72 h after reperfusion. Histochemical and molecular analyses demonstrate that OP-1: (a) minimizes infarction and cell necrosis, and decreases the number of plugged tubules; (b) suppresses inflammation by downregulating the expression of intercellular adhesive molecule, and prevents the accumulation and activity of neutrophils; (c) maintains the expression of the vascular smooth muscle cell phenotype in pericellular capillaries; and (d) reduces programmed cell death during the recovery. Collectively, these data suggest that OP-1 prevents the loss of kidney function associated with ischemic injury and may provide a basis for the treatment of acute renal failure.

Acute Kidney Injury↗
PubMed1998

Effect of fiber length on glass microfiber cytotoxicity.

Fiber length has been implicated as a determinant of fiber toxicity. Fibers of narrowly defined length can be generated by dielectrophoretic classifiers. Since the quantities of fibers produced are very small, we developed a rat alveolar macrophage microculture system to study the toxicity of these samples. The objective of this study was to examine the role of fiber length on the cytotoxicity of Manville code 100 (JM-100) fibers. Rat alveolar macrophages were cultured with 0-500 microg/ml of 5 lengths of JM-100 fibers on 96-well plates. After 18 h, well supernatants were removed and lactate dehydrogenase (LDH) activity was measured to assess cell damage. Chemiluminescence (CL), an assessment of macrophage function, was measured by adding lucigenin with or without zymosan, a particulate stimulus, to appropriate wells. For each fiber length the effects were concentration dependent: CL declined and LDH rose with increasing fiber concentration. Comparing the effects of different lengths showed the greatest toxicity from a relatively long fiber sample (mean length = 17 microm). Microscopic examination of the interaction of fibers with macrophages revealed multiple macrophages attached along the length of the long fibers. This suggests that frustrated, or incomplete, phagocytosis may be a factor in the increased toxicity of longer fibers. Overall the results demonstrate that length is an important determinant of toxicity for JM-100 fibers.

Acridines↗
PubMed1998

Prognosis of patients treated with whole-brain radiation therapy for metastatic gestational trophoblastic disease.

We evaluated the effect of multiple treatment- and disease-related variables on the outcome of patients receiving whole-brain radiation therapy (WBRT) for metastatic gestational trophoblastic disease (GTD). Between November 1967 and December 1994, 21 patients were treated at our institution for GTD metastatic to the brain. All received WBRT, of median 2200 cGy (range 200-3600 cGy). Median follow-up, from date of diagnosis of brain metastases, was 77 months (range 11-170 months). The 5-year actuarial local control of initial brain metastases with > or = 2200 cGy was 91%, compared to 24% with < 2200 cGy (P = 0.05). The 2- and 5-year actuarial survivals of the 9 patients whose disease was controlled at extracranial sites were 100 and 83%, respectively, compared to 8 and 0%, respectively, for the 12 whose extracranial disease was not controlled (P = 0.0002). Four (33%) of the patients with persistent or progressive extracranial disease later developed new sites of brain metastases, compared to 0% of the patients whose extracranial disease was controlled (P = 0.05). Eleven patients progressed at their initial site(s) of brain metastasis or developed new intracranial lesions; 6 of them died of brain metastases. Survival of patients with GTD metastatic to the brain is excellent if extracranial disease can be controlled. The total dose of radiation is critical in achieving control of initial brain metastases. Patients with uncontrolled extracranial disease are more likely to develop new brain metastases. Salvage of intracranial failures after WBRT is rare.

Actuarial Analysis↗
PubMed1998

Medication side effects in anxious patients: negative placebo responses?

The purpose of the present study was to detect any problems among anxious patients in switching from alprazolam to extended release alprazolam. Fifty-four patients with an anxiety disorder, stabilized on alprazolam, entered the study. During the first 2 weeks, all patients took alprazolam as usual. During the second 2 weeks, they all took the same dosage of the extended release formulation. They were evaluated weekly with standard clinical measures and were asked to report any adverse medical events. The clinical measures showed modest, steady improvement over the course of the study. Patients reporting adverse medical events increased from 26% of the sample to 60% after the switch of dosage forms. Most of these events were anxiety-like (48%) or sedative (37%). Patients who developed sedative events took slightly higher mean doses of alprazolam. Patients who developed anxiety-like events had higher baseline scores on the Somatization, Anxiety and Phobia clusters of the SCL-90. The results suggest that more anxious patients confronted with a change of regimen commonly generate anxiety symptoms that they attribute to the medication, i.e., negative placebo responses, perhaps especially if they have a tendency toward somatization. A study designed to sort out pharmacological and psychological effects and further explore the mechanisms at work is indicated.

Acute Disease↗