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Biomedical subjects

J A Bennett

Publications and source records attributed to J A Bennett.

At least 73 records · Page 4Linked to original sources
PubMed1995

"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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

Correlation of in vitro and in vivo growth suppression of MCF-7 human breast cancer by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The purpose of this study was to compare the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the in vitro and in vivo 17 beta-estradiol (E2)-dependent growth of MCF-7 human breast cancer cells. In culture, a major component of postconfluent growth of MCF-7 cells is E2 dependent. In vivo, MCF-7 cells fail to grow as xenografts without exogenous E2 support. Thus the effect of TCDD on postconfluent MCF-7 growth in culture was compared with its effect on MCF-7 xenograft growth in immunosuppressed mice. A concentration of 10(-9) M E2 was optimal for supporting postconfluent growth of MCF-7 cells in culture into multicellular aggregates (foci) on a monolayer background. The 50% inhibitory dose of TCDD under these conditions was 3 x 10(-10) M, while E2-dependent focus development was completely inhibited by 10(-8) M TCDD. Weekly i.p. administration of TCDD (5 micrograms/kg) to mice bearing MCF-7 tumor xenografts resulted in inhibition of the tumor growth rate for the first 2 weeks, followed by recovery to the control growth rate during the third week. These recovered tumors were found to retain estrogen-dependent growth as shown by second generation transplantation studies. The p.o. route of TCDD administration yielded a similar 2-week transient suppression of growth with a concentration of 8 micrograms TCDD/kg body weight but only a 1-week growth rate latency with a 2-microgram/kg body weight dose. A single 5-micrograms/kg dose given 1 day after implantation was virtually noninhibitory. These results indicate that TCDD suppression of estrogen-dependent MCF-7 human breast cancer cell growth in vitro was predicative of a similar growth suppression of MCF-7 solid tumor xenografts in vivo. However, additional host-related factors must be involved in vivo, since suppression of tumor growth is transient. These studies provide a basis for future in vivo investigations of TCDD endocrine toxicity by using the MCF-7 tumor as a surrogate estrogen-responsive human organ and to examine the efficacy of TCDD and related Ah receptor-mediated compounds in the management of human estrogen-dependent breast cancer.

Adenocarcinoma↗
PubMed1993

Valproate treatment of panic disorder and lactate-induced panic attacks.

Several lines of evidence suggest that the anticonvulsant drug valproate may have antipanic properties: (1) It enhances gamma-aminobutyric acid activity in the brain; (2) it has anxiolytic effects in animal models of anxiety; and (3) it has been reported to be effective in panic disorder in several preliminary studies; however, valproate has not been studied in the prevention of lactate-induced panic attacks. Sixteen patients with panic disorder underwent a lactate infusion followed by a 28-day treatment period with valproate and subsequent rechallenge with lactate. Response was measured by change in panic attack frequency and Hamilton Anxiety Scale (HAS) scores and by the ability of valproate to block lactate-induced panic on rechallenge. Of the 14 patients completing the 28-day trial, 10 (71%) experienced a greater than 50% reduction in the weekly frequency of panic attacks. Six (43%) had complete remission. HAS scores dropped significantly from a baseline mean of 30.8 +/- 9.4 (SD) to 12.6 +/- 7 after 4 weeks of treatment. Valproate blocked reinduction of panic symptoms on lactate rechallenge in 10 (83%) of 12 patients who had initially experienced panic symptoms on initial infusion. The significant reduction in spontaneous panic attacks and the blockade of lactate-induced panic symptoms by valproate support earlier studies suggesting that the drug may be an effective treatment for panic disorder.

Adult↗
PubMed1993

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↗
PubMed1993

Valproate as a loading treatment in acute mania.

Evidence from earlier studies indicates that the antimanic action of valproate becomes most apparent within 1-4 days of achieving serum concentrations 50 micrograms/ml, that valproate can be orally loaded with achievement of therapeutic serum concentrations within the first several days of treatment, there is a rapid onset of response, and minimal side effects. To provide further data on the safety and efficacy of valproate oral loading in the treatment of acute mania, we evaluated 13 consecutive patients with acute manic syndromes who received valproate initiated at a dosage of 20 mg/kg/day. In most cases, valproate was added to other psychotropics. All 13 patients received at least 5 full days of valproate maintained at or above 20 mg/kg/day, and valproate serum concentrations were 50 micrograms/ml (mean +/- SD = 88 + 25) by the second or third day of treatment. Ten (77%) patients displayed a moderate or marked response. Side effects were infrequent and minor. Consistent with our earlier study, these findings suggest that valproate can be safely administered via a loading dose of 20 mg/kg/day to patients with acute mania, including those on other psychotropics, and that it may produce a rapid response with minimal side effects.

Acute Disease↗
PubMed1993

Antiepileptic drugs for the treatment of panic disorder.

Evidence from preclinical studies, preliminary clinical reports, pharmacologic challenge studies and a small number of controlled trials suggests that several antiepileptic agents--valproate, carbamazepine, and clonazepam--may have therapeutic effects in the treatment of patients with panic disorder. We review the theoretical basis and available clinical data supporting the use of these agents in panic disorder.

Anticonvulsants↗
PubMed1993

Valproate oral loading in the treatment of acute mania.

BACKGROUND: Evidence from earlier studies suggests that the antimanic activity of valproate becomes most pronounced within 1 to 4 days of achieving serum concentrations of 50 mg/L or greater. We conducted a prospective study to assess the onset of antimanic activity of oral loading dosages of valproate administered to achieve serum concentrations above 50 mg/L within 24 hours. METHOD: Nineteen patients with bipolar disorder, manic phase, received divalproex sodium 20 mg/kg/day in divided dosages for 5 days, without other psychotropic agents except lorazepam up to 4 mg/day. Serum valproate concentrations were measured after 1 and 4 days of treatment. Improvement was measured daily by a blind rater using the Young Mania Rating Scale (MRS). RESULTS: Serum valproate concentrations greater than 50 mg/L were reached in all 15 patients completing the study. Ten (53%) of the 19 patients who received at least one complete loading dose displayed a significant (greater than 50%) reduction in MRS scores by study termination. These responders displayed the greatest percent change in MRS scores over the first 3 days of treatment. Side effects were minimal. CONCLUSION: Valproate can be safely administered by oral loading and may produce rapid onset of antimanic response in some patients.

Acute Disease↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗