Re: AIDS, nurses' intentions, and the interpretation of findings.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
J A Bennett
Publications and source records attributed to J A Bennett.
Topology profile for a glutamate receptor: three transmembrane domains and a channel-lining reentrant membrane loop.
We investigated the transmembrane topology of the GluR3 subunit that was translated in rabbit reticulocytes supplemented with microsomal membranes. A prolactin reporter epitope was fused to GluR3 at six locations, bracketing each of the proposed transmembrane domains. The sidedness of the epitope in the microsomal membrane was then assessed by proteinase K sensitivity. The N terminus and the entire region between M3 and M4 was extracellular, and the C terminus was intracellular by this method. Four native N-linked glycosylation sites in the amino terminus and one introduced site between M3 and M4 were utilized, confirming the extracellular location of these regions. Epitopes inserted upstream and downstream of M2 were protease sensitive and thus intracellular. Our results support a topological model for glutamate receptor subunits that consists of three transmembrane domains, M1, M3, and M4, and another domain, the proposed channel-lining M2, which forms a reentrant membrane segment with both ends facing the cytoplasm.
Animals↗
Desflurane controls the hemodynamic response to surgical stimulation more rapidly than isoflurane.
STUDY OBJECTIVE: To compare the control of hemodynamic response to surgical stimulus of desflurane to that of isoflurane. DESIGN: Prospective randomized study. SETTING: Operating room of a major U.S. teaching hospital. PATIENTS: 59 ASA status I, II, and III patients 18 to 80 years of age and were undergoing orthopedic or intra-abdominal surgical procedures of 1 or more hours in duration. INTERVENTIONS: Group 1 (n = 29) received desflurane in oxygen (O2) for their surgical procedure. Group 2 (n = 30) received isoflurane in O2 for their surgical procedure. Thiopental sodium 4 mg/kg and fentanyl 3 micrograms/kg provided induction; vecuronium 0.1 mg/kg facilitated intubation. Prior to incision the volatile anesthesia drug was titrated to maintain systolic blood pressure (SBP) within 20% of preinduction (baseline) values. Any time after incision, an SBP increase greater than 20% of baseline was treated with a 30% increase in inspired anesthetic concentration for 3 minutes, or until SBP was within 10% of baseline. Another three 30% increases were allowed at 3 minute intervals to return SBP to 10% of baseline. If four 30% increases did not return SBP to 10% of baseline, additional fentanyl up to 5 micrograms/kg or labetalol in 5 mg increments was given. MEASUREMENTS AND MAIN RESULTS: Measurement of hemodynamics and anesthetic concentration occurred every 2 minutes prior to skin incision and every 5 minutes thereafter. Measurement of hemodynamics and anesthetic concentration occurred every minute during treatment of blood pressure (BP) response to surgical stimulus. Desflurane allowed for more rapid control of BP response to surgical stimulus median 2 minutes (range 1 to 12 minutes) for desflurane versus 6 minutes (range 1 to 12 minutes, p = 0.011). The desflurane group required fewer 30% incremental anesthetic increases than the isoflurane group (1.8 versus 2.5, p = 0.016) to control increased SBP. End tidal/inspired drug concentration ratios were closer to unity in the desflurane patients both before (0.94 versus 0.80) and after (0.86 versus 0.70) changes in drug concentration to treat increased SBP. CONCLUSIONS: Anesthetic depth can be more rapidly titrated with desflurane compared to isoflurane. Alveolar/inspired concentration ratio approaches unity more rapidly with desflurane anesthesia.
Adolescent↗
Desflurane and the unmodified mass spectrometer.
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Anesthesia, Inhalation↗
Acquired immunodeficiency syndrome and social disease.
The social construction of disease and responses to it has implications not only for how nurses approach caregiving responsibilities but also for how we strategize for and participate in prevention efforts and elaborate priorities for advocacy. Historical review of responses to public health threats, along with critical examination of current social constructions of disease and public health practice, can inform our theory building and offer important insights for educators and clinicians striving to improve the care of people with acquired immunodeficiency syndrome (AIDS). Understanding what underlies responses is key to effecting changes. Although unique, AIDS has commonalities with other diseases and public health threats, past and present. Thus lessons learned from the past may be applicable to the current situation.
Acquired Immunodeficiency Syndrome↗
"Methodological notes on empathy": further considerations.
This article updates and extends Jeannette Gagan's "Methodological notes on empathy," published in the January 1983 issue of ANS. The evolving conceptualization of empathy as a complex, intrapsychic, and interpersonal process suggests that the inconclusiveness and apparent contradictions of research to date might be substantially clarified by considering data from a multidimensional perspective. Attention to the conceptual bases underlying diverse measurement approaches is key to understanding the data produced. Notwithstanding the limitations of their paradigms and models for nursing, the debates and knowledge accumulated in other disciplines can inform a broad range of inquiry relevant to nursing.
Education, Nursing↗
Systemic effects of salbutamol and salmeterol in patients with asthma.
BACKGROUND: Knowing the extent of the systemic effects of a new beta 2 agonist relative to an established drug is important for the prediction and interpretation of side effects. A recent study in which the effect of cumulative doses of salbutamol was compared with single doses of salmetreol suggested that, weight for weight, salmeterol may be up to 10 times more potent than salbutamol. This current study was designed to investigate further the dose equivalence of salmeterol and salbutamol. METHODS: Twelve patients with mild asthma inhaled cumulative doses of placebo, salmeterol 25, 50, 100, and 200 micrograms, and salbutamol 100, 500, 1000, and 1000 micrograms on separate days at hourly intervals in a randomised double blind crossover study. Changes in forced expiratory volume in one second (FEV1), heart rate, plasma potassium concentration, systolic and diastolic blood pressure were measured. Dose equivalence was determined as the dose ratio of salmeterol to salbutamol for the 50% maximum response to salbutamol. RESULTS: No important changes occurred in any measurements following placebo. Salmeterol and salbutamol caused a near maximum increase in FEV1 following the first dose so the dose equivalence for the airway effects could not be estimated. Heart rate increased and plasma potassium concentration and diastolic blood pressure decreased in a dose dependent manner following salmeterol and salbutamol, with median dose equivalences for salmeterol compared with salbutamol of 17.7, 7.8, and 7.6, respectively. CONCLUSIONS: These results confirm that the systemic activity of salmeterol compared with salbutamol is higher than would be expected from in vitro data, particularly for heart rate. Whether this is because of the relatively high dose of salmeterol used or pharmacokinetic differences between the two drugs is uncertain.
Adult↗
Desmopressin for risperidone-induced enuresis.
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Administration, Intranasal↗
Purification of alpha-fetoprotein from human cord serum with demonstration of its antiestrogenic activity.
Alpha-fetoprotein (AFP) was purified from pooled human cord serum to determine whether it would be similar to purified mouse AFP in its ability to be transformed into an antiestrogen by incubation with estradiol (E2). Greater purity was attained with a three-step purification procedure of chromatofocusing, Blue-Sepharose chromatography and immunoaffinity chromatography than with a two-step procedure of polyacrylamide gel electrophoresis followed by Blue-Sepharose chromatography. Nevertheless, both procedures rendered AFP in a form that was transformable by E2 to an antiestrogen, although the product of the three-step procedure afforded more consistent biological activity. Removal of albumin from AFP was crucial for transformation of AFP to an antiestrogen. Thus, human AFP is similar to mouse AFP in being transformed to an antiestrogen upon incubation with E2, even though there is only 66% structural homology between the two proteins, and human AFP lacks the high-affinity binding site for E2 present in the mouse AFP molecule.
Animals↗
Conflict with less distress: promoting team effectiveness.
As nurses increasingly turn to teamwork as a viable option for accomplishing a myriad of duties and responsibilities, they are discovering that teamwork can also be a source of conflict and stress. This article suggests that conflict is both inevitable and necessary within a team. A model of conflict is presented that aims not at reducing conflict, but at making it less distressing and thus more effective. The authors trace the influence of pre-conflict conditions and perspective-taking on conflict and ultimately team effectiveness. Finally, to apply the conflict model to practice, two examples are presented demonstrating both an ineffective and an effective use of conflict.
Conflict, Psychological↗
The pharmacokinetics of 125I-atrial natriuretic factor in anaesthetized rats. Effects of neutral endopeptidase inhibition with candoxatrilat and of ANF-C receptor blockade.
The effects of candoxatrilat (cis-4-([2-carboxy-3-(2-methoxyethoxy)propyl]-1-cyclopentanecarbonyla mino)- 1-cyclohexane carboxylic acid) and the ring-deleted atrial natriuretic factor (ANF) analogue C-ANF4-23 (des[Gln18, Ser19, Gly20, Leu21, Gly22]ANF4-23-NH2) on the clearance of (3-[125I]iodotyrosyl28)ANF (125I-ANF) were studied in both intact and nephrectomized anaesthetized rats. HPLC analysis was used to verify that the 125I-labelled material isolated by solid phase extraction of rat plasma was intact ANF. In intact animals, clearance of 125I-ANF was biphasic with a T1/2 alpha of 17 sec and T1/2 beta of 95 sec. Volume of distribution (Vd) was 564 mL/kg and plasma clearance (Clp) 248 mL/min/kg. Candoxatrilat, over the dose range 0.01-10 mg/kg i.v., increased T1/2 beta (by a maximum of 56%) and decreased Clp (by up to 52%) with no effect on T1/2 alpha or Vd. C-ANF4-23 (10 micrograms/kg+1 microgram/kg/min i.v.) reduced Vd (by 57%) and Clp (by 54%) with no effect on T1/2 beta, whilst abolishing the T1/2 alpha phase in over 50% of animals. Increasing the dose of C-ANF4-23 did not increase the effect on any of these parameters, apart from a small increase in T1/2 beta. Combining the two agents resulted in a substantial decrease in Clp (76%) whilst the reduction in Vd and increase in T1/2 beta were comparable to those seen with C-ANF4-23 and candoxatrilat alone, respectively. In nephrectomized rats, the pharmacokinetics of 125I-ANF and the changes induced by candoxatrilat were similar to those observed in intact animals, whilst the effects of C-ANF4-23 alone were greater than in intact animals. The combination of C-ANF4-23 and candoxatrilat again produced a substantial increase in T1/2 beta (153%) and decreases in Vd (55%) and Clp (78%) in nephrectomized animals, although these changes could not be distinguished from those seen in intact animals treated with the same combination. Our studies indicate that neutral endopeptidase and ANF-C receptors are both major, and approximately equal, clearance mechanisms for 125I-ANF, together accounting for at least 75% of the total clearance of this peptide in the rat.
Amino Acid Sequence↗
Assessment of the in vivo immunosuppressive activity of the major cyclosporine metabolite by leukemia allograft rejection.
AM1 (M17) is the major metabolite of cyclosporine found in the blood of human transplant recipients, and trough levels of this derivative exceed those of the parent compound approximately two-fold. Studies performed in vitro indicate that AM1 retains only 10-20% of the biological activity of the parent compound, but very little is known about its in vivo immunosuppressive effects. We therefore developed a rapid and sensitive method, based on the rejection of allogeneic L1210 (H-2d) leukemia cells by C57BL/6 (H-2b) mice, to assess the immunosuppressive activity of AM1 in vivo. Rejection of the leukemia allograft was determined by analyzing the spleens from mice injected intravenously with 10(5) L1210 cells for the presence of H-2Kd-positive cells by flow cytometry using an FITC-conjugated monoclonal anti-H-2Kd antibody. Nonimmunosuppressed mice rejected the allogeneic cells and survived indefinitely. Spleens from these mice were virtually free of H-2Kd-positive cells (0.51 +/- 0.21%) by day 7. In contrast, C57BL/6 mice treated with 10 mg/kg/day s.c. of CsA all died from the L1210 challenge (mean survival time of 9 +/- 1 days). Spleens from mice treated in this manner contained 11.02 +/- 3.31% H-2Kd-positive cells on day 7. There was a direct correlation between the dose of CsA administered (7.5-50 mg/kg/day) and the percentage of H-2Kd-positive cells in the spleen. We then compared the immunosuppressive activity of AM1 and CsA in this model. AM1 was purified from the urine of CsA-treated renal allograft recipients by a combination of preparative adsorption-desorption chromatography and preparative elution high-performance liquid chromatography. AM1 at a dose of 10 mg/kg/day exhibited no demonstrable immunosuppressive effect, and trough levels of AM1 on day 7 were only 36 +/- 4 ng/ml. Increasing the dose of AM1 to 50 mg/kg/day resulted in only 1.05 +/- 0.16% H-2Kd-positive cells in the spleens (P = NS) and a mean trough level of 221 +/- 27 ng/ml. In contrast, mice treated with 50 mg/kg/day of CsA exhibited 17.7 +/- 2.9% H-2Kd-positive cells in their spleens and a mean trough CsA level of 3036 +/- 277 ng/ml. The half-life of a single subcutaneous dose of 10 mg/kg of AM1 (4.6 hr) was significantly shorter than that of CsA (9.7 hr) in mice. Compared with CsA, the lack of immunosuppressive effect of AM1 in vivo therefore appears to be due to a combination of decreased immunosuppressive activity and increased rate of clearance in mice.
Animals↗
Acute cholesterol responses to mental stress and change in posture.
BACKGROUND: Serum lipid levels vary widely within individuals, but the causes of these fluctuations are poorly understood. One area of research concerns elevations in cholesterol concentration in response to emotional stress. In a laboratory-based experiment, we compared the effects of acute mental stress and postural change (standing) on serum cholesterol concentration. In addition, plasma volume was indirectly monitored to determine whether cholesterol changes with mental stress, if present, were a function of hemoconcentration. METHODS: Twenty-six men attended two laboratory sessions, each consisting of baseline (30 minutes), task (20 minutes), and recovery (30 minutes) periods. Subjects rested in the supine position during the baseline and recovery periods. During the task period of one session, subjects performed a mental task (Stroop test and mental arithmetic); during the other session, the subjects stood for the task period. RESULTS: Both mental stress and standing elicited significant elevations in heart rate, blood pressure, and plasma catecholamine concentrations, relative to the baseline and recovery periods. Both the mental and orthostatic tasks also significantly increased serum cholesterol concentration (by 0.10 and 0.57 mmol/L [3.7 and 21.9 mg/dL], respectively), as well as hemoglobin level and hematocrit. Cholesterol elevations with standing were reversible, while those resulting from mental stress persisted through the recovery period. When values were corrected for concomitant hemoconcentration, no net change in serum cholesterol level occurred during either task. CONCLUSIONS: Acute mental stress can produce rapid elevations in serum cholesterol concentration. It can also increase hemoglobin concentration and hematocrit (ie, reduce plasma volume). Therefore, increases in serum cholesterol level after acute mental stress are analogous to those with standing and may reflect hemoconcentration rather than altered lipoprotein metabolism.
Adolescent↗
The atriopeptidase inhibitor (+/-) candoxatrilat reduces the clearance of atrial natriuretic factor in both intact and nephrectomized rats: evidence for an extrarenal site of action.
We have demonstrated that in anaesthetized rats. (+/-) candoxatrilat reduces the clearance of both 125IANF and ANF 5-28, and prolongs the elimination half-life. These effects occur independent of glomerular filtration, since they are not attenuated by nephrectomy. Moreover, they cannot be attributed to blockade of ANF-C receptors. Our findings suggest that (+/-)candoxatrilat exerts its activity in vivo by specific inhibition of atriopeptidase at both renal and extra-renal locations.
Animals↗
Estrogen-stimulation of postconfluent cell accumulation and foci formation of human MCF-7 breast cancer cells.
Foci, nodules of cellular overgrowth, that appear after confluence are an in vitro characteristic of malignant transformation. A well-studied in vitro model of estrogen-dependent tumors is the MCF-7 cell line, derived from a pleural metastasis of a human breast adenocarcinoma. We report that cultivation of MCF-7 cells, using routine methods, results in extensive estrogen-stimulated postconfluent cell accumulation characterized by discrete three-dimensional arrays. Side view Nomarski optical sections revealed these to be principally multicellular foci with occasional domes and pseudoacinar vacuoles. This effect on MCF-7 cell growth occurs in media containing fetal bovine serum but not with calf serum or charcoal-dextran-treated fetal bovine serum unless supplemented with estrogens. Foci formation starts 5-6 days after confluence, and the number of foci generated is a function of the concentration of added estrogens. Foci formation is suppressed by the antiestrogens Tamoxifen and LY 156758. Addition of progesterone, testosterone, or dexamethasone had little or no effect, while various estrogens (ethinyl estradiol, diethylstilbestrol, and moxestrol) induced foci development. Clones derived from single cells of the initial MCF-7 population revealed a wide variance in estrogen-induced foci formation, demonstrating heterogeneity of this tumor cell line. The postconfluent cell growth of the estrogen receptor-deficient cell line, MDA-MB-231, contrasted with MCF-7 by developing an extensive multilayer morphology devoid of discrete structures. The tumorigenic potential of the MCF-7 cells used in our experiments was confirmed by their estrogen-dependent growth in immunosuppressed male BDF1 mice. These data suggest an estrogen receptor-based mechanism for the development of multicellular foci during postconfluent growth of MCF-7 cells. After confluence, foci, in contrast to the quiescent surrounding monolayer, retain proliferating cells. Focus formation, therefore, reflects the heterogeneous responsiveness of these cells to estrogens and should provide a model permitting in vitro comparisons between the progenitor cells of multicellular foci and the monolayer population.
Adenocarcinoma↗
Inhibition of neutral endopeptidase (EC 3.4.24.11) leads to an atrial natriuretic factor-mediated natriuretic, diuretic and antihypertensive response in rodents.
1. Atrial natriuretic factor is metabolized by neutral endopeptidase (atriopeptidase; EC 3.4.24.11) in vitro. Inhibitors of this enzyme have been reported to prolong the half-life of atrial natriuretic factor in vivo and to potentiate the renal and haemodynamic effects of exogenous atrial natriuretic factor. 2. (+/-)-Candoxatrilat, a selective neutral endopeptidase inhibitor, potentiated the natriuretic and diuretic response to volume loading in anaesthetized rats. Part of the response to volume loading and the potentiation by (+/-)-candoxatrilat was prevented by a polyclonal atrial natriuretic factor antiserum. The diuretic and natriuretic responses evoked by hydrochlorothiazide were not altered by the antiserum. 3. (+/-)-Candoxatrilat reduced systolic blood pressure of one-kidney deoxycorticosterone acetate-salt hypertensive rats for over 5 h. This response was abolished by pretreatment with atrial natriuretic factor antiserum. 4. These data demonstrate that the neutral endopeptidase inhibitor (+/-)-candoxatrilat has natriuretic/diuretic and antihypertensive effects in rodents, and that these effects are mediated via endogenous atrial natriuretic factor.
Animals↗
Inhibition of estrogen-dependent breast cancer growth by a reaction product of alpha-fetoprotein and estradiol.
Reaction of picomolar quantities of human or rodent alpha-fetoprotein (AFP) with nanomolar quantities of 17 beta-estradiol (E2) generates a product of unknown structure, designated AFP/E2, that inhibits estrogen-stimulated growth of mouse uterus. We describe herein the effect of rodent AFP/E2 on the in vivo growth of two estrogen-dependent breast cancers, the MCF-7 human breast cancer and the MTW9A rat mammary cancer. Both cancers were grown as xenografts under the kidney capsule of cyclosporine-immunosuppressed male BDF1 mice. In addition, the MTW9A tumor was grown as a homograft in syngeneic ovariectomized Wistar-Furth female rats. Estrogen support was provided by s.c. Silastic E2 implants. Injecting AFP/E2 that was generated by incubating 1.0 microgram of AFP with 0.5 microgram of E2 for 1 h at room temperature resulted in cessation of growth and, in most cases, regression of MCF-7 tumor xenografts. It also produced regression of MTW9A tumor homografts and significantly inhibited growth of MTW9A xenografts. Treatment with AFP alone or E2 alone did not inhibit growth of these tumors. The data suggest that AFP/E2 has a unique property which causes attenuation or shut-down of the biochemical reactions through which estrogen-dependent tumor growth is mediated.
Animals↗
Anticholinergic serum levels and cognitive performance.
Integrity of central cholinergic neurotransmission is essential for adequate cognitive functioning. Many psychotherapeutic medications have anticholinergic side-effects. In order to determine the impact of circulating anticholinergic activity on cognitive performance, 28 geropsychiatric inpatients underwent cognitive testing at different levels of anticholinergic serum activity. In 10 subjects with a diagnosis of probable Alzheimer's disease, significant deterioration of selected cognitive functions was observed at anticholinergic serum levels that caused no dysfunction in the 18 non-demented subjects. The data suggest that non-demented elderly patients with psychiatric problems tolerate psychotropic pharmacotherapy without significant negative impact on their cognitive competency. By contrast, patients with Alzheimer's disease are at risk of additional impairment. The introduction of anticholinergic serum activity as a monitoring technique for safe psychopharmacotherapy in geriatric patients is discussed.
Aged↗