Cross-cultural adaptation to cesarean birth.
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Biomedical subjects
Publications and source records attributed to J Fawcett.
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It has been widely accepted that in kidney, degradation of insulin occurs in lysosomes. It is thought that after internalization into the cell, insulin dissociates from its receptor, which then recycles to the plasma membrane, while the hormone is transported in endosomes to the lysosomes, where it is degraded. However, earlier studies from this laboratory have suggested that insulin may also be degraded in an extralysosomal site, most likely endosomes. Indeed, studies in other tissues, most notably liver, have shown that insulin degradation does take place in endosomes. Since the intracellular processing of insulin differs between different tissues and cell types, and as the kidney is a major site of insulin degradation, we set out to determine directly whether endosomes degrade internalized insulin in the kidney. Rats were injected with [125I]monoiodoinsulin, labeled at either the A14 or B26 tyrosine. After killing, the kidney cortex was excised, and heavy endosomes were prepared by differential and isopycnic centrifugation. The isolated [125I]insulin-loaded endosomes were incubated for up to 60 min in intracellular medium, and degradation of [125I] insulin was estimated by means of precipitation in trichloroacetic acid. In the presence of ATP (10 mM), the percent degraded was increased over the control value (no ATP present), but under these circumstances, degradation was greater when the endosomes contained internalized 125I-labeled [B26]insulin than with A14-labeled [125I]insulin (26% vs. 13% degraded/h). In the absence of ATP, the percent degraded increased when the pH of the incubation medium was lowered. Radiolabeled material was extracted from endosomes, and Sephadex G-50 analysis revealed the presence of high mol wt, insulin-size, and low mol wt material. Reverse phase HPLC analysis of the insulin-size material revealed the presence of intact insulin and a number of degradation products. The elution profiles of some of these products were consistent with that reported to arise from the action of the insulin-degrading enzyme. Western blot analysis with the antiinsulin-degrading enzyme monoclonal antibody 9B12 confirmed the presence of the enzyme in endosomal preparations. We conclude that degradation of insulin does occur in kidney cortical endosomes, probably involves the insulin-degrading enzyme, and results in the formation of relatively large intermediate products as well as low mol wt products.
Our preliminary studies of the efficacy of lithium carbonate therapy for alcoholism under double-blind, placebo-controlled conditions demonstrated that alcoholics who took their assigned medication (lithium or placebo) for the first 6 months after discharge from an inpatient rehabilitation program were more likely to abstain from any alcohol use for 18 months following discharge than were alcoholics who took their medication erratically or not at all. Attendance at Alcoholics Anonymous (AA) meetings was also associated with medication adherence. We applied a structural equation model to data on the relationships between medication adherence, AA meeting attendance and abstinent outcome to clarify whether medication adherence or AA meeting attendance better explains the positive-outcome "adherence effect" we observed. Both medication adherence and AA meeting attendance evidenced direct and independent influences on abstinent outcome: medication adherence showed a small direct influence, and AA meeting attendance showed a much larger, independent influence.
Double-blind, controlled clinical trial data were evaluated to assess a hypothetical relationship between fluoxetine and suicidality (suicidal acts and ideation) in patients with mood (n = 5,655) and nonmood disorders (n = 4,959) (Mantel-Haenszel incidence difference method). In mood disorders, act rates (suicide attempts/completions) were low (treatment differences nonsignificant). Substantial suicidal ideation emerged less frequently with fluoxetine than placebo and was comparable with fluoxetine and tricyclic antidepressants. Improvement in ideation was greater with fluoxetine than placebo; it was comparable with fluoxetine and tricyclic antidepressants (United States trials) and greater with tricyclic antidepressants than fluoxetine (international trials). In nonmood disorders, no suicides occurred. Act and emergent ideation rates were low (treatment differences nonsignificant). Results do not suggest a causal relationship between pharmacotherapy and emergence of suicidality. Fluoxetine or tricyclic antidepressants reduce suicidal ideation and may protect against the emergence of substantial suicidal ideation.
BACKGROUND: Anticonvulsants have been shown to be effective in many patients with psychiatric disorders, especially those with bipolar affective disorder. We present our clinical experience with divalproex sodium in the treatment of 63 patients with a variety of affective disorders that had proved refractory to conventional pharmacotherapy. METHOD: We reviewed the charts of 63 patients diagnosed as bipolar I (35 patients), bipolar II (23 patients), or schizoaffective, bipolar type (5 patients). Twelve patients who appeared to have recurrent unipolar depression had a retrospectively recognized history of "covert cycling," with brief periods of socially acceptable hypomania occurring between depressive episodes. Prior to treatment with divalproex, 45 patients had been classified as treatment failures with lithium, 29 patients had been classified as treatment failures with carbamazepine, and 35 patients had also failed on a combination of lithium and carbamazepine. Divalproex was given to these patients and titrated to achieve blood levels in the range of 50 to 100 mg/L. RESULTS: Forty-seven (75%) of the 63 patients responded positively to the addition of divalproex to their regimens. Of 45 patients who had failed to respond to lithium, 38 (84%) responded when divalproex was added. Of 29 patients who had failed to respond to carbamazepine, 20 (69%) responded when divalproex was added. Of 26 rapid-cycling patients, 21 (81%) responded to the addition of divalproex. Side effects required drug withdrawal in 9 patients (14%). CONCLUSION: The results confirm previous findings that both mania and rapid mood cycling may respond to a pharmacologic regimen that includes divalproex. Many patients who appear to have recurrent, major unipolar depression may actually be convert cyclers who will respond to divalproex, sometimes in combination with an antidepressant medication.
Therapeutic efficacy for depression and panic disorder has been demonstrated with the triazolobenzodiazepine alprazolam. However, potentially serious adverse events, including depression and suicide attempts, have been reported in patients taking this medication. In this paper, reports addressing the association between each of these two events and benzodiazepine use in general and, more specifically, alprazolam use, are reviewed. We conclude that while these adverse events do occur in patients taking alprazolam, the causal relationship remains unclear and requires further study. Fortunately, these events are observed only rarely, so the prudent clinician may continue to safely prescribe this useful medication.
A pilot study was conducted to determine the feasibility of a large-scale study testing how cancer support groups (CSGs) with coaching affect adaptation to newly diagnosed, early-stage breast cancer. The investigators randomly assigned subjects (n = 64) to one of three treatment groups: a CSG with coaching, a CSG without coaching, or no CSG. Results of the pilot study indicated that the study intervention and methods of sample accrual and instrumentation were appropriate. Currently, a large-scale, randomized, controlled clinical trial is being conducted.
To study the distribution of fluoxetine and norfluoxetine in blood compartments we determined their concentrations in red cells and plasma after the addition of 500 ng/ml of each compound to human blood in vitro. Red cell and plasma fluoxetine concentrations were 493 +/- 79 ng/ml and 454 +/- 53 ng/ml, respectively (P > 0.1). To assess the potential implications of this distribution on routine monitoring of these compounds in plasma, we determined fluoxetine and norfluoxetine concentrations in red cells and plasma in 6 patients receiving various doses of fluoxetine. While in 4 patients the concentrations of fluoxetine and norfluoxetine in red cells and plasma were comparable, 2 patients had higher concentrations of both compounds in red cells. Variations in the distribution of fluoxetine and norfluoxetine in blood compartments are relatively small. Plasma levels may reflect the drug concentration in whole blood more reliably for fluoxetine and norfluoxetine than for tricyclic antidepressants.
The co-ordinated function of effector and accessory cells in the immune system is assisted by adhesion molecules on the cell surface that stabilize interactions between different cell types. Leukocyte function-associated antigen 1 (LFA-1) is expressed on the surface of all white blood cells and is a receptor for intercellular adhesion molecules (ICAM) 1 and 2 (ref. 3) which are members of the immunoglobulin superfamily. The interaction of LFA-1 with ICAMs 1 and 2 provides essential accessory adhesion signals in many immune interactions, including those between T and B lymphocytes and cytotoxic T cells and their targets. In addition, both ICAMs are expressed at low levels on resting vascular endothelium; ICAM-1 is strongly upregulated by cytokine stimulation and plays a key role in the arrest of leukocytes in blood vessels at sites of inflammation and injury. Recent work has indicated that resting leukocytes express a third ligand, ICAM-3, for LFA-1 (refs 11, 12). ICAM-3 is potentially the most important ligand for LFA-1 in the initiation of the immune response because the expression of ICAM-1 on resting leukocytes is low. We report the expression cloning of a complementary DNA, pICAM-3, encoding a protein constitutively expressed on all leukocytes, which binds LFA-1. ICAM-3 is closely related to ICAM-1, consists of five immunoglobulin domains, and binds LFA-1 through its two N-terminal domains.
We have used an antiserum raised against mouse 2.5S NGF to examine the involvement of endogenous neurotrophins in the collateral sprouting of septohippocampal fibers in the adult rat brain. The antiserum was administered intraventricularly. Immunocytochemical techniques indicated that the injected antibodies penetrated into brain tissue that included the basal forebrain, cortex, striatum, corpus callosum, and hippocampus. Unilateral lesioning of the entorhinal cortex was done to evoke the sprouting of the cholinergic septohippocampal fibers. At 8 days postlesion, the sprouting was much advanced, as evidenced by an increase in density of the acetylcholinesterase (AChE) staining in the outer molecular layer (OML) of the dentate gyrus and by the associated increase in the absolute number of AChE-positive fibers in the OML. As well, there was a widening of the inner molecular layer (IML), interpreted as being due to sprouting of noncholinergic axons in that region. In rats injected daily with anti-NGF or anti-NGF Fab fragments, no increase in AChE density, or in the population of AChE-positive fibers, was observed in the OML. In contrast, the widening of the IML seemed to be unaffected by the anti-NGF treatment. No changes were observed in the AChE related parameters in the dentate gyrus of nonlesioned animals treated similarly for 8 days with anti-NGF; there was, however, a decrease of choline acetyltransferase (ChAT) immunostaining in the ChAT-positive cells of the basal forebrain. Our findings and the confirmation that our polyclonal anti-NGF also recognizes other members of the NGF neurotrophin family, specifically brain-derived neurotrophic factor and neurotrophin-3, indicate that at least one of these neurotrophins plays a key role in the collateral sprouting of the cholinergic septohippocampal fibers (but not that presumed to occur within the IML) following an entorhinal cortex lesion.
Perception of the birth experience was examined in a sample of 106 women who had unplanned cesarean deliveries, 113 who had planned cesarean deliveries, and 254 who had vaginal deliveries. Vaginally delivered women had more positive perceptions than their unplanned cesarean counterparts (p < .001). There were no differences in perceptions between the unplanned and planned cesarean groups, or between the planned cesarean and vaginal groups. General anesthesia for cesarean delivery was associated with more negative perceptions than regional anesthesia, and regional anesthesia for vaginal delivery was associated with more negative perceptions than no or local anesthesia. Pain intensity and physical distress were negatively correlated with perceptions.
Cell adhesion molecules are complex protein and carbohydrate molecules of many different types found on the surfaces of all cells. They are important in many aspects of cell biology including development, differentiation, and motility. These processes are frequently disturbed in cancer and recent work has demonstrated that disturbances in cell adhesion molecule expression are also common in malignancy.
There is a reciprocal relationship between conceptual models of nursing and nursing practice. Conceptual models influence clinical nursing practice by specifying standards for and purposes of practice; identifying relevant clinical problems, settings for practice, legitimate recipients of nursing care, and the content for the nursing process; suggesting methods for delivery of nursing services; and by providing frameworks for clinical information systems, patient classifications systems and quality assurance programmes. Nursing practice, in turn, provides data that can be used to determine the credibility of the conceptual models. Sources of data from clinical practice for credibility determination include evaluations of nursing interventions, the recipient's perspective of nursing care and quality assurance reviews.
It has long been thought that metabolism of insulin by kidney proximal tubule cells takes place only in lysosomes. But previous studies with the perfused rat kidney and a proximal tubule-like cultured kidney cell line suggested that insulin degradation occurred in a nonlysosomal compartment. In this study we show that endosomes isolated from rat kidney cortex degrade insulin and that this process is ATP and pH dependent.
Both fibromyalgia and depression may be related to disturbed serotonin metabolism, and an association between the 2 disorders has been postulated. We measured 3H-imipramine binding (IB), a biochemical indicator of serotonin uptake, pretreatment, in 10 nondepressed women with fibromyalgia, 14 subjects with major depression, and 10 volunteer controls. Our objective was to determine if IB in the 2 patient groups differed and in the same direction from the control values. Compared with depressed women, IB was significantly lower both in the women with fibromyalgia and in the men with depression. However, no women with fibromyalgia or men with depression had IB levels that were significantly different from control women and men. There was a trend for higher IB levels in depressed compared to control women.