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Biomedical subjects

E Thomas

Publications and source records attributed to E Thomas.

At least 91 records · Page 5Linked to original sources

Measuring blood volume with fluorescent-labeled hydroxyethyl starch.

OBJECTIVES: To develop and evaluate a method for measuring blood volume using the dilution of a fluorescent-labeled hydroxyethyl starch. DESIGN: Laboratory and clinical investigation. SETTING: Biochemistry laboratory at the University of Cardiff. Hematology clinic, surgical ward and intensive care unit of the University Hospital of Wales. PATIENTS: Seventeen patients with suspected polycythemia. Eight patients who had undergone major surgery and/or were receiving intensive postoperative care. INTERVENTIONS: All surgical and postoperative care was provided by clinicians not involved in the study. Patients with suspected polycythemia were referred for blood volume measurement using labeled albumin and red blood cells. MEASUREMENT AND MAIN RESULTS: A proprietary brand of hydroxyethyl starch (Elohaes) was labeled with fluorescein isothiocyanate. Dilution of this compound in vivo was used for measuring blood volume, and the results were compared with those obtained using radiolabeled albumin and the considered criterion, radiolabeled red cells. The elimination of the labeled starch follows the same progress as that of the parent compound, indicating that the fluorescent tag is stable in vivo. The volume of distribution of the labeled starch is 2.5 mL/kg lower than that for labeled albumin (p = .05). Blood volume, measured from the dilution of fluorescent starch, is lower (4.9 mL/kg) than that measured with albumin (p = .048) but higher (6.61 mL/kg) than that measured with red blood cells (p = .0007). This latter difference may be even smaller at marginally higher doses of the fluorescent starch. CONCLUSION: These data support the view that hydroxyethyl starch provides a valid alternative to red cell labels as a means of calculating blood volume in patients. Labeling the starch with a fluorescent marker makes the assay procedure more sensitive and infinitely easier. The dose required is not high enough to affect the hemodynamic status of the patient.

Blood Volume↗

MAGPIE/EGRET annotation of the 2.9-Mb Drosophila melanogaster Adh region.

Our challenge in annotating the 2.91-Mb Adh region of the Drosophila melanogaster genome was to identify genetic and genomic features automatically, completely, and precisely within a 6-week period. To do so, we augmented the MAGPIE microbial genome annotation system to handle eukaryotic genomic sequence data. The new configuration required the integration of eukaryotic gene-finding tools and DNA repeat tools into the automatic data collection module. It also required us to define in MAGPIE new strategies to combine data about eukaryotic exon predictions with functional data to refine the exon predictions. At the heart of the resulting new eukaryotic genome annotation system is a reverse comparison of public protein and complementary DNA sequences against the input genome to identify missing exons and to refine exon boundaries. The software modules that add eukaryotic genome annotation capability to MAGPIE are available as EGRET (Eukaryotic Genome Rapid Evaluation Tool).

Alcohol Dehydrogenase↗

Occupational risk factors for shoulder pain: a systematic review.

OBJECTIVES: To systematically evaluate the available evidence on occupational risk factors of shoulder pain. METHODS: Relevant reports were identified by a systematic search of Medline, Embase, Psychlit, Cinahl, and Current Contents. The quality of the methods of all selected publications was assessed by two independent reviewers using a standardised checklist. Details were extracted on the study population, exposures (physical load and psychosocial work environment), and results for the association between exposure variables and shoulder pain. RESULTS: 29 Studies were included in the review; three case-control studies and 26 cross sectional designs. The median method score was 60% of the maximum attainable score. Potential risk factors related to physical load and included heavy work load, awkward postures, repetitive movements, vibration, and duration of employment. Consistent findings were found for repetitive movements, vibration, and duration of employment (odds ratio (OR) 1.4-46 in studies with method scores >/= 60%). Nearly all studies that assessed psychosocial risk factors reported at least one positive association with shoulder pain, but the results were not consistent across studies for either high psychological demands, poor control at work, poor social support, or job dissatisfaction. Studies with a method score >/=60% reported ORs between 1.3 and 4.0. Substantial heterogeneity across studies for methods used for exposure assessment and data analysis impeded statistical pooling of results. CONCLUSIONS: It seems likely that shoulder pain is the result of many factors, including physical load and the psychosocial work environment. The available evidence was not consistent across studies, however, and the associations were generally not strong. Future longitudinal research should evaluate the relative importance of each individual risk factor and the role of potential confounding variables-such as exposure during leisure time-to set priorities for the prevention of shoulder pain in occupational settings.

Bias↗

Increased synchrony with increase of a low-threshold calcium conductance in a model thalamic network: a phase-shift mechanism.

A computer model of a thalamic network was used in order to examine the effects of an isolated augmentation in a low-threshold calcium current. Such an isolated augmentation has been observed in the reticular thalamic (RE) nucleus of the genetic absence epilepsy rat from the Strasbourg (GAERS) model of absence epilepsy. An augmentation of the low-threshold calcium conductance in the RE neurons (gTs) of the model thalamic network was found to lead to an increase in the synchronized firing of the network. This supports the hypothesis that the isolated increase in gTs may be responsible for epileptic activity in the GAERS rat. The increase of gTs in the RE neurons led to a slight increase in the period of the isolated RE neuron firing. In contrast, the low-threshold spike of the RE neuron remained relatively unchanged by the increase of gTs. This suggests that the enhanced synchrony in the network was primarily due to a phase shift in the firing of the RE neurons with respect to the thalamocortical neurons. The ability of this phase-shift mechanism to lead to changes in synchrony was further examined using the model thalamic network. A similar increase in the period of RE neuron oscillations was obtained through an increase in the conductance of the calcium-mediated potassium channel. This change was once again found to increase synchronous firing in the network.

Action Potentials↗

Effects of 7 years of growth hormone replacement therapy in hypopituitary adults.

Short-term studies of GH replacement in adult hypopituitarism have usually demonstrated beneficial effects on body composition and circulating lipids, with neutral or occasionally adverse effects on glucose tolerance. Fasting hyperinsulinemia has been reported. GH effects on cardiac function have been variable. The effects of long-term GH therapy, taking into account the consequences of increasing age, are not fully known. Thirty-three hypopituitary, initially middle-aged adults were studied over a 7-yr period; 12 patients took GH therapy (mean, 0.7 mg daily) continuously (group A); 11 took GH for only 6-18 months, a minimum of 5 yr previously (group B); and 10 patients never received GH therapy (group C). Other pituitary replacement was maintained. Effects on anthropometry, body composition (by bioimpedance analysis, total body potassium, and dual energy x-ray absorptiometry), circulating lipids, glucose and insulin concentrations, cardiac 2-dimensional and Doppler echocardiography, and exercise tolerance were assessed before and after the treatment period. Continuous GH therapy had no significant effect on body weight, but it prevented the increase in waist circumference and waist to hip ratio that occurred in the patients without GH substitution (waist to hip ratio, group A, 0.87+/-0.08 at baseline, 0.85+/-0.09 at 7 yr; group B, 0.89+/-0.11 at baseline, 0.94+/-0.11 at 7 yr; P < 0.005 for GH effect; group C, 0.87+/-0.10 at baseline, 0.92+/-0.10 at 7 yr; P < 0.005 for GH effect). A GH-induced decrease in subscapular skinfold thickness was also observed. By bioimpedance analysis, GH therapy caused an increase in total body water and fat-free mass, and a decrease in the percent body fat. Although changes occurred with time in all groups, no significant additional GH therapy effects were observed on glucose tolerance, insulin concentrations, lipid levels, cardiac dimensions, echocardiographic diastolic function, or exercise tolerance. In conclusion, prolonged GH substitution in middle-aged hypopituitary adults causes a sustained improvement in body composition. Other benefits, e.g. on lipid levels and exercise tolerance, were not apparent at 7 yr when comparisons were made with GH-untreated hypopituitary controls. Potentially adverse effects on glucose tolerance and insulinemia did not develop with prolonged GH therapy.

Absorptiometry, Photon↗

Proportion positive for Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, Toxoplasma, and human immunodeficiency virus types 1 and 2 in heterophile-negative patients with an absolute lymphocytosis or an instrument-generated atypical lymphocyte flag.

OBJECTIVES: To determine the proportion of patients with evidence of an acute infection due to Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), Toxoplasma, or human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) in heterophile-negative patients with an absolute lymphocytosis or an instrument-generated atypical lymphocyte flag, and to develop a cost-effective testing algorithm for managing such heterophile-negative patients. DESIGN: We conducted a prospective investigation of 70 selected outpatients who tested negative for heterophile antibody in association with an absolute lymphocytosis or instrument-generated atypical lymphocyte flag. The control population consisted of 50 patients who were heterophile negative and had a normal absolute lymphocyte count and no instrument-generated atypical lymphocyte flag. SETTING: A large outpatient laboratory system. INTERVENTION: Viral serology for HHV-6 was performed by immunofluorescence, and all other serologies were performed by enzyme-linked immunoassay. All testing was for immunoglobulin (Ig) M antibodies, except in the case of HIV. RESULTS: The proportion of study patients positive for EBV was 40% (28/70); for CMV, 39% (27/70); for HHV-6, 25% (16/65); for Toxoplasma, 3% (2/70); and for HIV, 0% (0/70). All 50 control patients were negative for EBV IgM antibodies. When patients with more than 1 positive viral test were excluded from analysis, positivity was 20% (9/45) for EBV, 22% (10/45) for CMV, 9% (4/45) for HHV-6, and 2% (1/45) for Toxoplasma. Utilizing hypothesis-generating logistic regression models, Downey type II atypical lymphocytes were significantly associated with EBV positivity (P =.006), while Downey type III lymphocytes were significantly associated with HHV-6 positivity (P =.016), and there was a trend for the association of Downey type I lymphocytes with CMV positivity (P =.097). CONCLUSIONS: A positive viral serology was identified in 70% of study patients. Multiple positive serologies complicate establishing a definitive diagnosis. Potential cost savings may be associated with the use of an appropriate testing algorithm.

Adolescent↗

Autoimmune hepatitis--a diagnostic challenge.

Autoimmune hepatitis is a type of chronic hepatitis characterized by hypergammaglobulinemia, hypertransaminasemia, presence of autoantibodies, and active necroinflammatory process in the liver revealed by histology. Its onset is usually acute and has a bad prognosis. Tissue antibodies are found in large proportions of patients. Women outnumber men in a 2-3:1 ratio, and it is mostly young women who are affected. Ten percent of all affected have severe disease characterized by elevations of serum aminotransferase levels greater than five-fold, along with a two-fold elevation of gamma globulin or a 10-fold elevation of serum aminotransferase levels alone. We present an unusual case of this disorder in a 60-year-old male patient manifesting its severe form.

Diagnosis, Differential↗

Variation in the use of alternative levels of hospital care for newborns in a managed care organization.

OBJECTIVE(S): To assess the extent to which variation in the use of neonatal intensive care resources in a managed care organization is a consequence of variation in neonatal health risks and/or variation in the organization and delivery of medical care to newborns. STUDY DESIGN: Data were collected on a cohort of all births from four sites in Kaiser Permanente by retrospective medical chart abstraction of the birth admission. Likelihood of admission into a neonatal intensive care unit (NICU) is estimated by logistic regression. Durations of NICU stays and of hospital stay following birth are estimated by Cox proportional hazards regression. RESULTS: The likelihood of admission into NICU and the duration of both NICU care and hospital stay are proportional to the degree of illness and complexity of diagnosis. Adjusting for variation in health risks across sites, however, does not fully account for observed variation in NICU admission rates or for length of hospital stay. One site has a distinct pattern of high rates of NICU admissions; another site has a distinct pattern of low rates of NICU admission but long durations of hospital stay for full-term newborns following NICU admission as well as for all newborns managed in normal care nurseries. CONCLUSIONS: Substantial variations exist among sites in the risk-adjusted likelihood of NICU admission and in durations of NICU stay and hospital stay. Hospital and NICU affiliation (Kaiser Permanente versus contract) or affiliation of the neonatologists (Kaiser Permanente versus contract) could not explain the variation in use of alternative levels of hospital care. The best explanation for these variations in neonatal resource use appears to be the extent to which neonatology and pediatric practices differ in their policies with respect to the management of newborns of minimal to moderate illness.

Health Maintenance Organizations↗

[Cacchi and Ricci's disease. Radiology, epidemiology and biology].

OBJECTIVES: Medullary sponge kidney corresponds to the precaliceal dilatation of renal tubules. The purpose of this article is to draw attention to some of the radiological, epidemiological and laboratory features of this disease. MATERIAL AND METHOD: 500 cases of radiopaque renal stones, corresponding to 310 men and 190 women, were reviewed. One or several urographies, early urographic films, and blood calcium phosphate and 24-hour urinary calcium phosphate and oxalate assessments were available for all subjects. We have added to this series an identical study on 100 cases of stones in North African subjects. RESULTS: From a radiographic point of view, this study shows the value of early urography films, performed between the 2nd and 4th minutes after intravenous injection of iodinated contrast agent, which visualize abnormal opacification of the renal pyramids, before or at the same time as that of the bases of the calices. A radiological sign, not reported in the medical literature, is a clear border between abnormal opacification of the papillae and that of the calices, observed in one or several papillocaliceal zones, which facilitates the diagnosis of medullary sponge kidney. In this series of 500 cases of renal stones, the radiological diagnosis of medullary sponge kidney was established in 103 cases: 20.6%. The distribution varies according to sex, 54 out of 310 (12.59%) in men, 53 out of 190 (27.89%) in women; difference p < 0.001. We found only 3 cases of medullary sponge kidney in the series of 100 cases of radiopaque stones in North African subjects. In terms of laboratory parameters, 24-hour urine tests showed hypercalciuria in 61 out of 103 cases (59.22%), or hyperoxaluria in 66 out of 103 cases (64.08%), while 41 out of 103 cases (39.81%) presented both disorders. Urinary calcium oxalate assessments were normal in 20 out of 103 cases (19.42%). Hyperparathyroidism was never detected in combination with medullary sponge kidney. CONCLUSION: This study shows the value of early urography films for the diagnosis of medullary sponge kidney and demonstrates a useful diagnostic radiological sign: a clear border between abnormal urographic opacification of the papillae and calices. It shows the much higher frequency of medullary sponge kidney in patients with radiopaque stones, with a higher rate in women than in men, and a low frequency in North African subjects, that needs to be confirmed. This study also emphasizes the frequency of hypercalciuria and especially hyperoxaluria, and even the combination of these two disorders in medullary sponge kidney.

Female↗

Short-term physical risk factors for new episodes of low back pain. Prospective evidence from the South Manchester Back Pain Study.

STUDY DESIGN: A prospective population-based cohort study performed in South Manchester, United Kingdom. OBJECTIVES: To determine whether nonoccupational physical activity and indicators of physical stress on the spine predict low back pain in the short term. SUMMARY OF BACKGROUND DATA: There is evidence that physical activity outside the workplace helps to protect against low back pain in the long term. However, such activity may injure or stress the spine in the short term. METHODS: A baseline survey questionnaire identified 2715 adults, aged 18-75 years, with no low back pain at the time of the survey. Information on potential predictors of low back pain also was obtained. New episodes of back pain were identified during the subsequent year. RESULTS: A new low back pain episode occurred in 34% of men and 37% of women. Poor general health at baseline was the strongest predictor of a new episode of pain (men: relative risk (RR) 1.5, 95% confidence intervals (CI) 0.8, 2.7; women: RR 2.2, 95% CI 1.2, 4.0). High weight was associated with subsequent low back pain in women (RR 1.4; 95% CI 1.0, 2.0), but neither height nor weight predicted low back pain in men. A self-rated low level of physical activity was not consistently linked with subsequent low back pain, nor were specific nonoccupational physical activities, apart from home-improvement work in men and regular sports in women. CONCLUSION: Although some specific activities may be hazardous to the back, physical activity outside the workplace does not increase the short-term risk of low back pain overall. Leisure-time physical activity is not a hazard to the back, whereas poor physical health in both genders and heavier weight in women do increase the risk of new low back pain episodes in the short term.

Adult↗

Normal immune function of monocyte-derived dendritic cells from HIV-infected individuals: implications for immunotherapy.

Dendritic cells (DC) are the most potent cells involved in the generation of primary and secondary immune responses. To assess the feasibility of using autologous DC as immunotherapy for HIV disease, we analyzed a variety of immune parameters using DC isolated from HIV-infected (HIV+) individuals, as well as DC obtained from HIV-uninfected (HIV-) individuals infected in vitro with HIV. After stimulation with recombinant CD40 ligand (CD40LT), cytokine and beta-chemokine production were similar by DC from HIV- donors infected in vitro with the CCR5-using HIV Ba-L strain (n = 8) compared with uninfected DC from the same donors. Production of beta-chemokines, but not of cytokines, was increased by a CXCR4-using IIIB strain-infected DC (n = 7). Stimulation of HIV-infected DC with CD40LT decreased infection in Ba-L-infected DC, but had no effect on IIIB-infected DC. Consistent with this finding, CD40LT down-regulated CCR5 and up-regulated CXCR4 expression on DC. Monocyte-derived DC were also propagated from 15 HIV+ and 13 HIV- donors. They exhibited similar expression of costimulatory molecules and produced similar amounts of IL-12, IL-10, and beta-chemokines, following stimulation. By contrast, stimulated PBMC from HIV+ patients exhibited decreased IL-12 and increased IL-10 production. In summary, phenotype, cytokine secretion, and beta-chemokine production by DC from HIV+ individuals were normal. These cells may prove useful in boosting cellular immune responses in HIV+ individuals.

Adoptive Transfer↗

Predicting who develops chronic low back pain in primary care: a prospective study.

OBJECTIVES: To quantify the relative contribution of premorbid and episode specific factors in determining the long term persistence of disabling symptoms of low back pain. DESIGN: Prospective cohort study. SETTING: Two general practices in the south Manchester area. PARTICIPANTS: 180 patients, who previously participated in a cross sectional population survey, who consulted because of low back pain during the study period. They were followed at 1 week and 3 and 12 months after consultation. MAIN OUTCOME MEASURE: Persistent disabling low back pain in the 12 months after the consultation. RESULTS: Disabling low back pain persisted in one third of participants after consultation and was more common with increasing age, among those with a history of low back pain, and in women. Persistence of symptoms was associated with "premorbid" factors (high levels of psychological distress (odds ratio 3.3; 95% confidence interval 1.5 to 7.2), poor self rated health (3.6; 1.9 to 6.8), low levels of physical activity (2.8; 1.4 to 5.6), smoking (2. 1; 1.0 to 4.3), dissatisfaction with employment (2.4; 1.3 to 4.5)) and factors related to the episode of low back pain (duration of symptoms, pain radiating to the leg (2.6; 1.3 to 5.1), widespread pain (6.4; 2.7 to 15), and restriction in spinal mobility). A multivariate model based on six factors identified groups whose likelihood of persistent symptoms ranged from 6% to 70%. CONCLUSIONS: The presence of persistent low back pain is determined not only by clinical factors associated with pain but also by the premorbid state.

Adolescent↗

Regulation of macrophage IL-12 synthesis by Leishmania phosphoglycans.

It is now generally accepted that IFN-gamma, secreted by Th1 cells, is the most potent cytokine leading to macrophage activation and host resistance against infection with the intracellular protozoan parasite Leishmania. It is also established that IL-12 is a critical cytokine involved in the differentiation and expansion of Th1 cells. Therefore, the ability of Leishmania parasites to actively suppress IL-12 production by host macrophages may be an important strategy for parasite survival. Here we report that a major parasite cell surface molecule, phosphoglycan (PG), of Leishmania could selectively inhibit the synthesis of IL-12(p40, p70) by activated murine macrophages. Furthermore, synthetic PG (sPG) was able to inhibit IL-12 release in a dose-dependent manner. Inhibition was dependent on the galactose(beta1-4)mannose(alpha1)-PO4 repeating units and not the glycophosphoinositol lipid anchor of lipophosphoglycan. At the concentration used, sPG had no effect on the release of TNF-alpha or IL-6 in activated macrophages. The inhibition of IL-12(p40) production was at the transcriptional level, but was not mediated through NF kappaB inhibition. These data demonstrate that PG may be an important molecule for the establishment and survival of the parasite in permissive hosts.

Animals↗

Cat-scratch disease simulating a malignant process of the chest wall.

UNLABELLED: Cat-scratch disease is a well-known cause of regional adenopathy in immunocompetent children. Rarely, patients may present with symptoms simulating a neoplastic disease. The case of a 12-year-old boy with fever, swelling of the chest wall and hepatosplenic nodules is reported. Histological analysis of biopsy specimen obtained from the chest wall lesion and the liver revealed granulomatous reaction without malignant cells. Serological investigations were positive for Bartonella species. The symptoms and the lesions disappeared after oral antibiotic therapy (ciprofloxacin) was started. The patient remained symptom-free 12 months later. CONCLUSION: The present case emphasizes the wide spectrum of clinical manifestations associated with cat-scratch disease which should be investigated as differential diagnosis of manifestations suggesting a neoplastic disease in children.

Bartonella↗

Predictors of early improvement in low back pain amongst consulters to general practice: the influence of pre-morbid and episode-related factors.

Low back pain symptoms are extremely common. affecting as many as 80% of the population at some time in their lives. However, the majority of the medical costs arise from the minority of patients whose symptoms become chronic. The authors propose a model in which chronicity is determined not only by factors related to the episode of low back pain, but also factors prior to the onset of symptoms (pre-morbid factors). No previous study has collected information on predictors of low back pain chronicity prior to the onset of symptoms. Participants in the South Manchester Low Back Pain Study, recruited by means of a cross-sectional population survey were followed prospectively over 18 months to identify those who consulted their general practitioner with a new episode of low back pain. At interview, 1-2 weeks post-consultation, it was determined whether or not subjects' symptoms had improved. In males, low levels of psychological distress, a higher than average reported level of physical activity, being in employment, and being satisfied with current work status were associated with a quick improvement in symptoms. In addition factors related to the episode, namely a short duration before consultation and symptoms with a sudden onset and confined to the lower back area, also strongly predicted a good early outcome. Using information on both pre-morbid and episode related factors, groups of male patients were identified whose probability of an early resolution of symptoms ranged between 0.25 and 1. Few factors, either pre-morbid or episode-related, were strongly associated with outcome amongst females. This large population-based study has shown, despite the known heterogeneity in the origin of low back pain and the pathologies associated with symptoms, an early improvement in symptoms amongst male attenders at general practice can be predicted on the basis of a small number of variables.

Adolescent↗