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Biomedical subjects

E Nelson

Publications and source records attributed to E Nelson.

At least 19 recordsLinked to original sources
PubMed2000

A randomized, controlled, phase II trial comparing escalating doses of subcutaneous interleukin-2 plus antiretrovirals versus antiretrovirals alone in human immunodeficiency virus-infected patients with CD4+ cell counts >/=350/mm3.

A total of 73 patients with baseline CD4+ cell counts >/=350 cells/mm3 who were receiving combination antiretroviral therapy (ART) were randomized to receive subcutaneous interleukin-2 (IL-2; n=36) in addition to ART or to continue ART alone (n=37). Subcutaneous IL-2 was delivered at 1 of 3 doses (1.5 million international units ¿MIU, 4.5 MIU, and 7.5 MIU per dose) by twice-daily injection for 5 consecutive days every 8 weeks. After 24 weeks, the time-weighted mean change from baseline CD4+ cell count was 210 cells/mm3 for recipients of subcutaneous IL-2, compared with 29 cells/mm3 for recipients of ART alone (P<.001). There were no significant differences between treatment groups for measures of plasma human immunodeficiency virus RNA (P=.851). Subcutaneous IL-2 delivered at doses of 4.5 MIU and 7.5 MIU resulted in significant increases in CD4+ cell count (P=.006 and P<.001, respectively), compared with that seen in control patients. These changes were not significant in the 1.5 MIU dose group compared with that in the control patients (P=.105). Side effects that occurred from subcutaneous IL-2 administration were generally low grade, of short duration, and readily managed in an outpatient environment.

Adult↗
PubMed2000

Diclofenac treatment prolongs renal transit time in acute ureteral obstruction: a renographic study.

OBJECTIVE: Prostaglandin inhibitors, mostly diclofenac, are currently first-choice therapy for ureteral colic, their main action being reduction of intrapelvic pressure and diuresis. We hypothesized that diclofenac, by increasing tubular reabsorption, can delay excretion of contrast medium and give a false impression of severe obstruction. METHODS: Gamma camera renography was performed with 50 MBq (99)Tc(m)-MAG3 before and with 150 MBq 30 min after intramuscular injection of 75 mg diclofenac in 10 patients with acute ureteral colic. The time to maximum isotope activity in each kidney, T(max), was compared with T(max) in 10 control patients, who did not receive diclofenac but underwent two identical renographies. RESULTS: T(max) was significantly delayed after diclofenac, from 353 s at baseline to >1,200 s on the stone side, and from 225 to 465 s on the healthy side. Without diclofenac there was no T(max) retardation between the two renographies. CONCLUSION: Diclofenac treatment can lead to overestimation in ureteral stone disease, by delaying renal excretion bilaterally, but predominantly on the side of calculus.

Acute Disease↗
PubMed2000

Exposure to suggestion and creation of false auditory memories.

The experiment investigated the possibility of creating false auditory memory through exposure to suggestion. Research by Loftus and others has indicated that, through suggestion, false memories can be created. Participants viewed a short film and were given a 9-item questionnaire. Eight questions were used as filler while one question asked respondents to recall a phrase one character had said. Although the character actually said nothing, 23 of 30 respondents recalled having heard him speak and specifically recalled his words. This statistically significant result shows that auditory memories can also be created.

Adolescent↗
PubMed1999

The impact of the geometry of the lithotriptor aperture on fragmentation effect at extracorporeal shock wave lithotripsy treatment.

The aim of this study was to determine the impact of the aperture size of an electro-hydraulic lithotriptor on the fragmentation effect. We also wanted to investigate whether a potential change in the capacitance of the pulse forming network (PFN), at a certain energy level, might have an impact on fragmentation rate. Two different apertures with a diameter of 23 and 17 cm respectively were compared using two different values of total PFN capacitance: 50 nF and 80 nF. Model stones of similar size and weight were fragmented. The number of shots for complete fragmentation or the grade of fragmentation after a certain number of shots was measured. This study shows that for the shock wave system used, the 23-cm aperture seems to provide more effective fragmentation as function of the number of shots compared with the 17-cm aperture at the same energy level. Furthermore, a minor change in the PFN capacitance between reasonable limits does not affect the fragmentation efficiency. This article also highlights the fact that it is not relevant simply to compare the voltage level given in the shots in extracorporeal shock wave lithotripsy treatment between different lithotriptors.

Electric Conductivity↗
PubMed1999

Maternal passive smoking during pregnancy and fetal developmental toxicity. Part 1: gross morphological effects.

1. Prenatal exposure of human fetus to tobacco smoke through maternal passive smoking has been epidemiologically linked to reduced birth weight, enhanced susceptibility to respiratory diseases and changes in immune system. However, no data exists indicating teratogenicity of involuntary smoking. Since sidestream smoke of cigarettes makes the most constituent of whole smoke inhaled by nonsmokers, we performed experiments to determine whether passive inhalation of sidestream smoke by rats causes malformations in newborns. 2. Pregnant 230 - 300 g Wistar rats were each placed in a 150 dm3 glass chamber with two holes, each 3 cm in diameter in two opposite walls to provide unforced exchange of fresh air. A third hole was connected to an automatic smoking machine. The head of a commercial filter blond cigarette (13 mg Tar, 0.9 mg Nicotine) was introduced to the chamber through this later hole. Cigarettes were smoked by smoking machine at the rate and volume resembling human smoking and the mainstream smoke was separately collected and discarded. Each rat thus received the sidestream smoke self-diluted in the chamber air. Experiments were performed with either 1, 2, 3 or 4 cigarettes/day during either first, second or third week of a total 21-day pregnancy period. The interval between smoking of cigarettes was 2 h. 3. COHb in blood of negative controls was about 1.2% and after exposure to 1 or 4 cigarettes were 6% and 12.2%, respectively. A dose-dependent reduction of birth weight was observed in newborns (P<0.001); bitemporal diameters and body lengths were reduced accordingly. No macroscopically visible gross anomaly could be observed. After removing the fat tissue and staining the skeleton with alizarin, a widespread ossification retardation could be observed in all exposed groups regardless of the dose. Such a retardation was not limited to a particular bone. 4. These results support epidemiologic data on developmental toxicity of passive smoking and further provide evidence on an unfavorable osteopathic effect of sidestream exposure of mother on fetal development.

Animals↗
PubMed1999

Maternal passive smoking during pregnancy and foetal developmental toxicity. Part 2: histological changes.

1. Evidence has been accumulating on the growth suppressing effects of maternal passive smoking on foetus. Reviewing all literature released during the last two decades and screening for all possible variables such as previous smoking history, maternal age and weight gain, parity and length of gestation, placental weight, and diet, we found no reason to doubt the role of passive smoking during pregnancy in the induction of growth retardation. However, no literature indicates whether these birthweight deficits might hint at other possible hidden abnormalities in tissues. To verify this question, we performed an experiment on rats. 2. We have already reported that pups born to rats with previous exposure to cigarette's sidestream smoke during pregnancy showed a significant and dose-dependent growth retardation. Those pregnant rats were exposed each in a 150 dm3 glass chamber to diluted sidestream smoke of either 1, 2, 3 or 4 commercial blond filter brand cigarettes during either first, second or third week of pregnancy. We have selected a part of each group of pups at random and examined for possible histological changes of lung, liver, stomach, kidney and intestinal tissues. 3. Compared to controls, lung tissues of newborns of smoke exposed mothers showed an enhanced incidence of apoptosis, mesenchymal changes, and hyperplasia of bronchial muscles. Pronounced abnormal changes in haematopoiesis and proliferation of bile duct cells were the most variations from norm observed in liver tissues of exposed pups. Immature glomeruli of kidney, epithelhypoplasia of stomach, and hypoplasia of intestinal villi were common among newborns of exposed mothers than among controls. 4. These results indicate that passive smoking upon pregnancy causes abnormal morphological changes in internal tissues of newborns. At present, we can draw no conclusion as to whether these histological changes will result in functional malformations or possibly late effects, although they should be expected.

Animals↗
PubMed1998

Model sclerotization studies. 4. Generation of N-acetylmethionyl catechol adducts during tyrosinase-catalyzed oxidation of catechols in the presence of N-acetylmethionine.

Incubation of catechol with mushroom tyrosinase in the presence of N-acetylmethionine resulted in the generation of an adduct. This product was identified to be N-acetylmethionyl catechol, on the basis of spectral characteristics and well-characterized chemical reaction of o-benzoquinone with N-acetylmethionine. Enzyme-catalyzed oxidation of catechol and the subsequent nonenzymatic addition of the resultant quinone to N-acetylmethionine accounted for the observed reaction. That the reaction is not confined to catechol alone, but is of general occurrence, can be demonstrated by the facile generation of similar adducts in incubation mixtures containing N-acetylmethionine, tyrosinase, and different N-acetylmethionines, such as 4-methylcatechol and N-acetyldopamine. Attempts to duplicate the reaction with insect cuticular phenoloxidases were not successful, as the excess N-acetylmethionine used in the reaction inhibited their activity. Nevertheless, occurrence of this nonenzymatic reactivity. Nevertheless, occurrence of this nonenzymatic reaction between N-acetylmethionine and mushroom tyrosinase-generated quinones indicates that a similar reaction between enzymatically generated quinones in the cuticle with protein-bound methionine moiety is likely to occur during in vivo quinone tanning as well.

Animals↗
PubMed1998

Efficacy and safety of tolterodine in patients with detrusor instability: a dose-ranging study.

OBJECTIVE: To investigate the efficacy and safety of tolterodine, a new antimuscarinic agent, and define the optimum dosage in patients with symptoms of detrusor instability (urgency, increased frequency of micturition and/or urge incontinence). PATIENTS AND METHODS: A double-blind, placebo-controlled, multicentre study was carried out; after a 1-week run-in period to establish baseline values, 81 patients were randomized to receive placebo or tolterodine 0.5, 1, 2 or 4 mg twice daily for 2 weeks. Micturition (diary) variables, urodynamics and subjective urinary symptoms were assessed after 2 weeks' treatment. RESULTS: A per-protocol analysis of efficacy in 64 patients showed dose-related improvements in recorded micturition and urodynamic variables, e.g. at a dosage of 2 mg twice daily, the frequency of micturition, episodes of incontinence and pad use were reduced by 20%, 46% and 29%, respectively, while the volume at first contraction increased by 89 mL. The 4 mg dosage was associated with a large increase in residual urinary volume and an increased incidence of dry mouth. The incidence of adverse events (mainly mild or moderate antimuscarinic effects) was comparable with placebo at tolterodine dosages of < or = 2 mg. No serious adverse events were observed and tolterodine had no clinically significant impact on electrocardiographic or laboratory findings. CONCLUSION: The results indicate that tolterodine offers an effective treatment for the symptoms of detrusor instability. The optimum dosage appears to be 1-2 mg twice daily.

Adult↗
PubMed1998

Looking at care from the inside out: a conceptual approach to geriatric care.

Today, managing care from the "outside in" is the predominant model for changing health care. The risk of this outside-in approach is that the health care system may lose sight of the people and communities for which it serves and cares. In this article, an "inside-out" model for viewing health care in a geriatric population is presented from the perspective of patients and providers, placing the provider in a proactive rather than reactive role. By focusing attention on the outcomes or value a patient is experiencing, providers are challenged to consider new ways of managing care.

Aged↗
PubMed1998

Phase I trial of anti-CD3-stimulated CD4+ T cells, infusional interleukin-2, and cyclophosphamide in patients with advanced cancer.

PURPOSE: We performed a phase I trial to determine whether in vivo expansion of activated CD4+ T cells was possible in cancer patients. 111Indium labeling was used to observe trafficking patterns of the infused stimulated CD4+ T cells. The influence of cyclophosphamide (CTX) dosing on immunologic outcome was also examined. PATIENTS AND METHODS: Patients with advanced solid tumors or non-Hodgkin's lymphoma received CTX at 300 or 1,000 mg/m2 intravenously (i.v.). Leukapheresis was performed to harvest peripheral-blood mononuclear cells (PBMCs) either just before the CTX dose, or when the patient was either entering or recovering from the leukocyte nadir induced by CTX. An enriched population of CD4+ T cells was obtained by negative selection. The CD4+ T cells were activated ex vivo with anti-CD3, cultured with interleukin-2 (IL-2) for 4 days, and adoptively transferred. After adoptive transfer, patients received IL-2 (9.0 x 10(6) IU/m2/d) by continuous infusion for 7 days. RESULTS: The absolute number of CD4+, CD4+/DR+, and CD4+/CD45RO+ T cells increased in a statistically significant fashion in all cohorts after the first course of therapy. The degree of CD4 expansion was much greater than CD8 expansion, which resulted in a CD4:CD8 ratio that increased in 26 of 31 patients. The greatest in vivo CD4 expansion occurred when cells were harvested as patients entered the CTX-induced nadir. One complete response (CR), two partial responses (PRs), and eight minor responses were observed. Trafficking of 111Indium-labeled CD4 cells to subcutaneous melanoma deposits was also documented. CONCLUSION: CD4+ T cells can be expanded in vivo in cancer patients, which results in increased CD4:CD8 ratios. The timing of pheresis in relation to CTX administration influences the degree of CD4 expansion. Tumor responses with this regimen were observed in a variety of tumors, including melanoma and non-Hodgkin's lymphoma; a high percentage of patients had at least some tumor regression from the regimen that produced the greatest CD4+ T-cell expansion.

Adult↗
PubMed1997

Construction of a full-length Ca2+-sensitive adenylyl cyclase/aequorin chimera.

Ca2+-sensitive adenylyl cyclases are key integrators of Ca2+ and cAMP signaling. To selectively probe dynamic changes in [Ca2+]i at the plasma membrane where adenylyl cyclases reside, a full-length, Ca2+-inhibitable type VI adenylyl cyclase/aequorin chimera has been constructed by a two-stage polymerase chain reaction method. The expressed adenylyl cyclase/aequorin chimera was appropriately localized to the plasma membrane, as judged by biochemical fractionation and functional analysis. The chimera retained full adenylyl cyclase activity and sensitivity to inhibition by physiological [Ca2+]i elevation. The aequorin portion of the chimeric construct was also capable of measuring changes in [Ca2+] both in vitro and in vivo. When the plasma membrane-tagged aequorin and cytosolic aequorin were compared in their measurement of [Ca2+]i, they showed contrasting sensitivities depending on whether the [Ca2+]i originated from internal stores or capacitative entry. This is the first full-length enzyme-aequorin chimera that retains the full biological properties of both aequorin and a Ca2+-sensitive adenylyl cyclase. This novel chimeric Ca2+ sensor provides the unique ability to directly report the dynamics of [Ca2+]i that regulates this Ca2+-sensitive enzyme under a variety of physiological conditions. Since this chimera is localized to the plasma membrane, it can also be used to assess local changes in [Ca2+]i at the plasma membrane as distinct from global changes in [Ca2+]i within the cytosol.

Adenylyl Cyclases↗
PubMed1997

Exploring the TPQ as a possible predictor of antidepressant response to nefazodone in a large multi-site study.

Subjects in the midst of a major depressive episode completed the Tridimensional Personality Questionnaire (TPQ) prior to beginning an open trial of nefazodone. A multiple regression analysis was used to further examine the finding of Joyce et al. (1994; Temperament predicts clomipramine and desipramine response in major depression, J. Affect. Disord. 30 (1994) 35-46) that a model involving TPQ Reward Dependence and Harm Avoidance scores, and their interaction, significantly predicted treatment response. The model was found to have significant predictive value (R2 = 0.011, P = 0.0053), but to account for a trivial 1.1% of the variance. Individuals with high Reward Dependence scores had a significantly lower response rate when response was defined as a 60% reduction from baseline HAM-D score. Although the clinical utility of the present findings is uncertain, this line of investigation attempting to link temperament to pharmacological response represents a potentially useful future strategy.

Antidepressive Agents↗
PubMed1997

Management of the suicidal patient with schizophrenia..

No matter what the course of treatment determined to be most appropriate, suicidal behavior must be considered thoroughly, and it must be conveyed to the patient that the clinician can assist him or her through this period of increased distress. Hopelessness must be viewed as a symptom with the assumption that a more meaningful sense of purpose will emerge despite the chronic and potentially limiting nature of schizophrenia. Most people with schizophrenia are not suicidal, and most who are suicidal can be offered interventions that will reduce their symptomatology and thereby dissipate their suicidal behavior.

Combined Modality Therapy↗
PubMed1997

Stability of diagnosis of obsessive-compulsive disorder in the Epidemiologic Catchment Area study.

OBJECTIVE: This study examined the 1-year temporal stability of a National Institute of Mental Health Diagnostic Interview Schedule (DIS) lifetime diagnosis of obsessive-compulsive disorder in the Epidemiologic Catchment Area (ECA) study. METHOD: In that study, 20,862 individuals, aged 18 years and over, at five sites were evaluated by lay interviewers using the DIS (wave 1). All of those who were available 12 months later were reinterviewed (wave 2). In the present study, the temporal stability of wave 1 obsessive-compulsive disorder diagnoses at wave 2 was examined, as well as relationships with comorbid diagnoses. The consistency of reports of "new-onset" illness was also examined. Factors contributing to these measures were evaluated. RESULTS: The temporal stability of the diagnosis of obsessive-compulsive disorder was very low. Subjects with a stable diagnosis of obsessive-compulsive disorder had a higher rate of both obsessions and compulsions, an earlier age at onset, and more comorbid anxiety, affective, and alcohol abuse/dependence disorders at initial assessment. The originally reported 1-year incidence estimates for obsessive-compulsive disorder primarily reflect data from subjects at wave 2 who reported the onset of symptoms as preceding the wave 1 interview. Older and less-educated subjects had significantly higher error rates in reporting onset. CONCLUSIONS: The DIS diagnosis of obsessive-compulsive disorder has poor validity, leaving the true incidence and prevalence of the disorder unknown. Older and less-educated subjects require special attention in the design of instruments for use with community samples.

Adolescent↗