Does Internet-based guided-self-help for depression cause harm? An individual participant data meta-analysis on deterioration rates and its moderators in randomized controlled trials.

BACKGROUND: Almost nothing is known about the potential negative effects of Internet-based psychological treatments for depression. This study aims at investigating deterioration and its moderators within randomized trials on Internet-based guided self-help for adult depression, using an individual patient data meta-analyses (IPDMA) approach. METHOD: Studies were identified through systematic searches (PubMed, PsycINFO, EMBASE, Cochrane Library). Deterioration in participants was defined as a significant symptom increase according to the reliable change index (i.e. 7.68 points in the CES-D; 7.63 points in the BDI). Two-step IPDMA procedures, with a random-effects model were used to pool data. RESULTS: A total of 18 studies (21 comparisons, 2079 participants) contributed data to the analysis. The risk for a reliable deterioration from baseline to post-treatment was significantly lower in the intervention v. control conditions (3.36 v. 7.60; relative risk 0.47, 95% confidence interval 0.29-0.75). Education moderated effects on deterioration, with patients with low education displaying a higher risk for deterioration than patients with higher education. Deterioration rates for patients with low education did not differ statistically significantly between intervention and control groups. The benefit-risk ratio for patients with low education indicated that 9.38 patients achieve a treatment response for each patient experiencing a symptom deterioration. CONCLUSIONS: Internet-based guided self-help is associated with a mean reduced risk for a symptom deterioration compared to controls. Treatment and symptom progress of patients with low education should be closely monitored, as some patients might face an increased risk for symptom deterioration. Future studies should examine predictors of deterioration in patients with low education.

Red ear syndrome and auricular erythromelalgia: the same condition?

Several cases of relapsing attacks during which the ear becomes red and patients experience a burning sensation have been reported in the literature. This combination of symptoms has been described as 'red ear syndrome' (RES). We report on a 7-year-old boy who had episodes of reddening, swelling and a burning sensation in one ear with local hyperthermia persisting for 3 years. The differential diagnosis included RES and erythromelalgia, as isolated auricular variants of erythromelalgia have been described and the symptoms are difficult to distinguish from RES. In this report, we discuss the similarities and differences between RES and erythromelalgia.

Perturbation of C6 glial cells by acetate leads to modulation of [125I]IGF-II binding to the IGF-II/M6P receptor: implications for ligand internalization studies.

Acid washes are used as an experimental tool to differentiate between cell-surface bound and internalized radioligands. We have observed that washes with acid buffers containing 100 mM acetate can modulate [125I]IGF-II binding to rat C6 glial cells in an unexpected manner: when cells in monolayer culture were prewashed with phosphate buffered saline (pH 7.3) (PBS), [125I]IGF-II binding was characteristic of the IGF-II/mannose-6-phosphate (M6P) receptor. Importantly, IgG 3637, which is purified from an antiserum directed against the rat IGF-II/M6P receptor, blocked binding of [125I]IGF-II whereas nonimmune IgG did not. Affinity crosslinking studies using DSS as the crosslinking agent and Western blotting experiments using antiserum 3637 confirmed the presence of the IGF-II/M6P receptor in C6 glial cells. Prewashes of C6 cell monolayers with acid buffers (pH 4-4.5) which contained 100 mM sodium acetate and which have been used in internalization studies reduced [125I]IGF-II binding by 40-60%. Affinity crosslinking studies using C6 cells showed that the formation of the 250 kDa radioligand-receptor complex was not prohibited by IgG 3637 after acid washes with buffers containing high acetate concentrations, while acid washes with buffers containing no acetate did not cause a loss in the blocking ability of IgG 3637. However, acid washes with 100 mM acetate did not alter the recognition of IGF-II/M6P receptors by IgG 3637 in Western blotting experiments. In addition, in a subset of experiments acid prewashes with acetate also decreased binding of [125I]IGF-I to the IGF-I receptor by 20%. We conclude that acid washes with acetate buffers lead to decreased [125I]IGF-I and [125I]IGF-II binding. In addition, the capability of anti-receptor IgG to block radioligand binding to the IGF-II/M6P receptor also declines. We hypothesize that alteration of ligand binding might be partially caused by perturbation of the cell membrane and hence a conformational change in IGF receptors. These data imply that the use of acetate buffers in acid wash experiments in ligand internalization studies--particularly in studies involving the IGF-II/M6P receptor--should be avoided.

Identification and in situ localization of the insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor in the rat gastrointestinal tract: comparison with the IGF-I receptor.

In the present study we investigated pharmacological, biochemical, and immunological characteristics as well as the tissue distribution of the insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor in the rat gastrointestinal tract, and compared the data with those from corresponding experiments for the IGF-I receptor. Competitive binding and affinity cross-linking studies with [125I]IGF-II, and [125I]IGF-I respectively, in rat jejunum yielded results analogous to those previously obtained for IGF-II/M6P and IGF-I receptors in intestinal epithelial membranes and other tissues. Furthermore, the IGF-II/M6P receptor antibody no. 3637 completely inhibited the association of [125I]IGF-II with receptor protein but nonimmune antibody did not, providing additional evidence for the presence of the IGF-II/M6P receptor in the rat gut. Also, analysis of the IGF-II/M6P receptor by immunoblotting using antiserum no. 3637 identified a specific band of mol wt 220.000 throughout the gastrointestinal tract with the highest content of immunoreactivity being present in colon and ileum. Autoradiographic mapping of the distribution of IGF-receptors in the rat gut showed that the expression of IGF-II/M6P receptors was in general 2-3 times greater than that of IGF-I receptors. IGF-II/M6P receptors were found 1) in greatest densities in colon and ileum, 2) more abundantly in the mucosa than in the muscularis propria, and 3) predominantly in the luminal part of the mucosal epithelial cells. Radioimmunocytochemistry employing anti-IGF-II/M6P receptor antibody no. 3637 and [125I]protein A demonstrated an IGF-II/M6P receptor distribution analogous to that shown by autoradiography with [125I]IGF-II). IGF-I receptors were present 1) in greatest densities in ileum and colon, 2) more abundantly in the muscularis propria than in the mucosa, and 3) within the mucosa in greater densities in the lamina propria than in the surface epithelium. For both receptor types densities were greater in crypt than in villous epithelial cells. We conclude: 1) the presence of IGF-II/M6P receptors throughout the rat gastrointestinal tract points to an important role for IGF-II in this organ, 2) the finding of different patterns of distribution for IGF-II/M6P and IGF-I receptors supports the concept of their different principal functions, 3) a high degree of expression of both receptor types in crypt epithelium suggests an essential role for both IGF receptors in the regulation of cell mitogenesis and growth.

Identification and characterization of insulin-like growth factor receptors on adult rat cardiac myocytes: linkage to inositol 1,4,5-trisphosphate formation.

Cultured cardiac myocytes from adult Sprague-Dawley rats express both insulin-like growth factor-I (IGF-I) receptors and insulin-like growth factor-II/mannose 6-phosphate (IGF-II/Man6P) receptors and respond to IGF-I with a dose-dependent accumulation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and inositol 1,4-bisphosphate [Ins(1,4)P2]. Specific binding of [125I]IGF-I to isolated membranes from cultured cardiac myocytes amounted to 1-1.2%. Binding of [125I]IGF-I was inhibited by unlabeled IGF-I at nanomolar concentrations and insulin at much higher concentrations. These data suggest that IGF-I binds to its own receptor on rat cardiac myocytes. Competitive binding studies using isolated membranes from cardiac myocytes and [125I]IGF-II showed 2-4% specific binding. Binding of [125I]IGF-II was inhibited by IGF-II and much less potently by IGF-I and insulin. Immunoglobulin G (IgG) 3637 (an IgG directed against the IGF-II/Man6P receptor) partially inhibited binding of [125I]IGF-II whereas nonimmune IgG did not. Affinity cross-linking studies with [125I]IGF-II and cardiac myocyte membranes and subsequent analysis of the ligand-receptor complex using SDS-PAGE and autoradiography showed a radiolabeled band of approximately 250 kilodalton (kDa). The formation of the [125I]IGF-II-receptor complex was inhibited by incubation with IGF-II and IgG 3637 but not by insulin or nonimmune IgG. Western blotting of protein extracts from cultured cardiac myocytes was performed using IgG 3637 and an immunoperoxidase technique for the visualization of the IGF-II/Man6P receptor protein. A specific band at 220 kDa under nonreducing conditions was detected on the blots, providing further evidence for the expression of the IGF-II/Man6P receptor by cardiac myocytes. The effect of IGFs on the accumulation of inositol phosphates was measured by HPLC analysis of perchloric acid extracts from myo-[3H]inositol-labeled cultured cardiac myocytes. IGF-I (50 ng/ml) stimulated the accumulation both of Ins(1,4,5)P3 and Ins(1,4)P2 after 30 sec by 43% and 63%. IGF-II (up to 500 ng/ml) had no significant effect on inositol phosphate accumulation under the same conditions. However, in the presence of millimolar concentrations of Man6P, IGF-II (500 ng/ml) also increased Ins(1,4,5)P3 accumulation by 59%. We conclude that cardiac myocytes from adult rats express IGF receptors and respond to IGFs with the accumulation of Ins(1,4,5)P3 and Ins(1,4)P2. This effect seems to be mediated by an IGF-I receptor-specific pathway.

Characterization of ovine growth hormone (oGH) and ovine placental lactogen (oPL) binding to fetal and adult hepatic tissue in sheep: evidence that oGH and oPL interact with a common receptor.

The GH receptor (GHR) plays a key role in postnatal growth regulation. Although plasma concentrations of GH are high during fetal life, its role during fetal development is not well understood. Recent data suggest that GHR are present in fetal hepatic tissue as early as 51 days gestation. However, the levels of GHR expression are markedly lower in fetal hepatic tissue compared to postnatal values, and there are conflicting data suggesting that ovine placental lactogen (oPL) and oGH share a common receptor. Given the uncertainty about whether oPL acts via the oGHR or a distinct receptor, we performed ligand binding and affinity cross-linking studies on hepatic microsomal membranes from adult castrated male, pregnant female, and fetal sheep. Ligand binding assays at a constant concentration of membranes showed that [125I]oPL yielded consistently higher (P < 0.001) specific binding (59.5 +/- 6.4%, 30.5 +/- 5.7%, and 7.6 +/- 2.4% for castrated male, pregnant female, and fetal sheep, respectively) compared to [125I]oGH (17.8 +/- 4.7%, 5.0 +/- 1.6%, and 1.2 +/- 0.4% for castrated male, pregnant female, and fetal sheep, respectively). Cross-reactivity studies showed that unlabeled oPL was consistently more potent than unlabeled oGH in displacing either of the labeled ligands. The dissociation constant (Kd) for oPL binding ranged from 0.16-0.40 nM and was not changed by solubilization with Triton X-100. Equilibrium binding analysis for oGH showed lower affinity for hepatic microsomal membranes (Kd, 1.7-3.2 nM) in each of the three groups of animals. Affinity cross-linking of microsomal membranes from castrated male and pregnant female sheep liver showed four major cross-linked complexes with both [125I]oPL and [125I]oGH, with mol wt of 150, 97, 75, and 60 kilodaltons. All four bands were identified with both ligands. Unlabeled oPL showed markedly higher potency than unlabeled oGH in reducing the signal of the [125I]oPL cross-linked complexes, whereas unlabeled oGH and oPL showed comparable potencies in reducing the signal of the [125I]oGH complexes. Immunoprecipitation of detergent-solubilized hepatic microsomal membranes from pregnant and fetal sheep using a panel of monoclonal antibodies raised against the extracellular region of the rabbit GHR showed potent immunological recognition of the [125I]oPL-receptor complexes. We suggest that oGH and oPL bind to a common or a related receptor protein(s). It is possible that differences in receptor dimerization or association with other membrane proteins are the basis of the differences in affinity and biological actions of the two hormones.

Expression of the insulin-like growth factor-II/mannose-6-phosphate receptor in multiple human tissues during fetal life and early infancy.

The insulin like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor has been detected in many cells and tissues. In the rat, there is a dramatic developmental regulation of IGF-II/M6P receptor expression, the receptor being high in fetal and neonatal tissues and declining thereafter. We have systematically studied the expression of the human IGF-II/M6P receptor protein in tissues from 10 human fetuses and infants (age 23 weeks gestation to 24 months postnatal). We have asked 1) whether there is differential expression among different organs, and 2) whether or not the human IGF-II/M6P receptor is developmentally regulated from 23 weeks gestation to 24 months postnatal. Protein was extracted from human tissues using a buffer containing 2% sodium dodecyl sulfate and 2% Triton X-100. Aliquots of the protein extracts were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting using an anti-IGF-II/M6P receptor antiserum (no. 66416) and 125I-protein A or an immunoperoxidase stain. IGF-II/M6P receptor immunoreactivity was detected in all tissues studied with the highest amount of receptor being expressed in heart, thymus, and kidney and the lowest receptor content being measured in brain and muscle. The receptor content in ovary, testis, lung, and spleen was intermediate. The apparent molecular weight of the IGF-II/M6P receptor (220,000 kilos without reduction of disulfide bonds) varied among the different tissues: in brain the receptor was of lower molecular weight than in other organs. Immunoquantitation experiments employing 125I-protein A and protein extracts from human kidney at different ages revealed a small, albeit not significant, difference of the receptor content between fetal and postnatal tissues: as in other species, larger amounts of receptor seemed to be present in fetal than in postnatal organs. In addition, no significant difference of the receptor content between human fetal liver and early postnatal liver was measured employing 125I-protein A-immunoquantitation in three fetal and five postnatal liver tissue samples. The distribution of IGF-binding protein (IGEBP) species, another abundant and major class of IGF binding principles, was also measured in human fetal and early postnatal lung, liver, kidney, muscle, and brain using Western ligand blotting with 125I-IGF-II: as with IGF-II/M6P receptor immunoreactivity there was differential expression of the different classes of IGFBPs in the various organs.(ABSTRACT TRUNCATED AT 400 WORDS)

Biosynthetic labeling of beta-hexosaminidase B: inhibition of the cellular uptake of lysosomal secretions containing [3H]hexosaminidase B by insulin-like growth factor-II in rat C6 glial cells.

The insulin-like growth factor-II/mannose-6-phosphate receptor binds two classes of ligands, IGF-II and lysosomal enzymes containing the mannose-6-phosphate recognition marker. To study the interaction of the two classes of ligands at the receptor level, we have isolated 'high uptake' forms of lysosomal enzymes containing mannose-6-phosphate that had been radiolabeled biosynthetically using a tissue culture model: Tay-Sachs disease fibroblasts were incubated in medium containing [3H]mannose, ammonium chloride and mannose-6-phosphate. Under the conditions of these experiments, the Tay-Sachs disease fibroblasts synthesized and secreted radiolabeled hexosaminidase B, as confirmed by measuring enzymatic activity of cell-conditioned medium. The enzyme secreted was recognized by antibodies raised against purified hexosaminidase A and B but not by nonimmune control sera in Western blotting and immunoprecipitation experiments. The radiolabeled cell-conditioned medium was partially purified by ion-exchange chromatography on a DEAE-Sephadex column. When partially purified [3H]hexosaminidase B was incubated with rat C6 glial cells which express large numbers of IGF-II/mannose-6-phosphate receptors, the enzyme was taken up specifically via the IGF-II/mannose-6-phosphate receptor as evidenced by carbohydrate competition experiments. The specific uptake of the radiolabeled lysosomal enzyme was partially inhibited by IGF-II and an antibody against the IGF-II/mannose-6-phosphate receptor (No. 3637). We conclude that the cellular uptake of a biosynthetically labeled lysosomal enzyme, hexosaminidase B, is partially inhibited by IGF-II. We hypothesize that IGF-II might be capable of modulating lysosomal pathways in vivo.

Growth hormone (GH) status regulates GH receptor and GH binding protein mRNA in a tissue- and transcript-specific manner but has no effect on insulin-like growth factor-I receptor mRNA in the rat.

The effect of growth hormone-deficiency (GHD) and treatment with recombinant bovine GH (bGH) or human IGF-I (hIGF-I) for 10 days on the expression of GH receptor (GHR), GH binding protein (GHBP) and of insulin-like growth factor-I receptor (IGF-IR) mRNA was examined using dw/dw and normal Lewis rats. Hepatic GHR and GHBP mRNA expression was significantly lower in dw/dw rats in comparison to Lewis rats (P < 0.01) while specific 125I-bGH binding to hepatic microsomal membranes was significantly higher (P < 0.01), suggesting a reduction in hepatic GHR turnover with GHD. Treatment with bGH reduced hepatic specific 125I-bGH binding in dw/dw rats, but had no effect in Lewis rats. Treatment with hIGF-I increased hepatic specific 125I-bGH binding in Lewis rats. Hepatic GHR and GHBP mRNA expression was not changed by bGH or hIGF-I treatment, suggesting that differences in hepatic specific 125I-bGH binding may be due to posttranscriptional mechanisms. GHBP mRNA expression was higher in kidney, heart, and muscle of dw/dw rats in comparison to Lewis rats (P < 0.01), while GHR mRNA abundance was not changed. Treatment of dw/dw rats with hIGF-I or bGH resulted in a coordinate reduction of GHR and GHBP mRNAs in kidney (P < 0.01). IGF-IR mRNA was not detected in liver and despite reduced plasma IGF-I levels and IGF-I mRNA expression IGF-IR mRNA abundance was not changed in nonhepatic tissues by GHD. Our data suggest that changes in plasma IGF-I levels and local IGF-I mRNA do not influence IGF-IR mRNA expression, while GHR and GHBP mRNA expression in different rat tissues are regulated independently. The increased nonhepatic GHBP mRNA expression with GHD suggests that nonhepatic GHBP may have an important physiological function distinct from that of GHBP in liver or in plasma.

Quality of life in breast cancer. Part I: Physical and social well-being.

Almost 2 million breast cancer survivors reside in the United States. An increase in consumer advocacy and media attention to this disease has helped bring breast cancer survivorship to the forefront of public attention. This has led to increased attention on quality of life (QOL) issues for these survivors of breast cancer. This two-part article presents the results of a qualitative, descriptive study evaluating the QOL of 21 breast cancer survivors. This study is based on our conceptual model of QOL including physical, psychological, social, and spiritual well-being. Part I of this article describes the impact of breast cancer on the physical and social domains of QOL based on in-depth interviews with breast cancer survivors.

Quality of life in breast cancer. Part II: Psychological and spiritual well-being.

With an increasing number of women surviving breast cancer beyond treatment, the focus of care has shifted from the acute treatment-related side effects to long-term effects associated with changes in quality of life (QOL). Part I of this article described the impact of breast cancer on the domains of physical and social well-being of 21 long-term survivors of breast cancer through qualitative analysis. Part II explores the impact of breast cancer on the domains of psychological and spiritual well-being.

The insulin-like growth factor-II/mannose-6-phosphate receptor is present in fetal bovine tissues throughout gestation.

The insulin-like growth factor-II (IGF-II) and the IGF-II/mannose-6-phosphate (M6P) receptor are thought to play an important role in fetal growth and development. We have studied the expression of the IGF-II/M6P receptor in fetal bovine tissues from 5 through 36 weeks' gestation. Tissues from bovine fetuses were extracted in buffer containing 2% Triton-X-100 and 2% sodium dodecyl sulfate (SDS). Aliquots of the protein extracts were analyzed by SDS polyacrylamide gel electrophoresis and the protein bands were transferred onto nitrocellulose. Immunoblotting was performed with anti-bovine IGF-II/M6P receptor antiserum. In a subset of experiments, ligand blotting was carried out with radiolabeled IGF-II and subsequent autoradiography. IGF-II/M6P receptors were expressed in all tissues examined, with the highest amount of receptor being present in fetal lung and liver. Low amounts of receptors were measured in fetal brain. The amount of receptor was developmentally regulated throughout fetal life. The developmental regulation of receptor expression varied among the different tissues. In conclusion, the IGF-II/M6P receptor is present in all fetal bovine tissues examined. The presence of the IGF-II/M6P receptor seems to be developmentally regulated during bovine fetal life. We hypothesize that this receptor exerts important biologic effects during fetal growth and tissue and organ development.

Quality of life in breast cancer survivors: implications for developing support services.

PURPOSE/OBJECTIVES: Quality of life (QOL) is becoming more important in regard to breast cancer as treatment advances extend the period of survivorship. The purpose of this article is to share the results of a cancer center's attempt to evaluate the QOL needs of breast cancer survivors in order to provide improved supportive-care services. DESIGN: Descriptive mailed survey. SETTING: A medical center in southern California. SAMPLE: A random sample of breast cancer survivors (N = 298). METHODS: Breast cancer survivors completed a mailed survey that included major outcome variables of QOL and pain. Subjects were stratified by three age groups: younger than 40 years, 40-60 years, and older than 60 years. MAIN RESEARCH VARIABLES: QOL subscales (physical, psychological, social, and spiritual well-being) and overall QOL score and pain as assessed by the Brief Pain Inventory. FINDINGS: Results indicated continued physical demands of breast cancer, including fatigue and pain, as well as psychological burdens related to fear of breast cancer recurrence and anxiety. The social well-being domain indicated some unique aspects of QOL when applied to breast cancer survivorship such as the fear of breast cancer in female relatives. The spiritual well-being domain illustrated the unique QOL aspects of life-threatening illness such as living with uncertainty and maintaining hope. Breast cancer survivors also reported positive aspects and life changes after successfully facing breast cancer. CONCLUSIONS: Breast cancer survivors experience many demands of illness across the physical, psychological, social, and spiritual domains. IMPLICATIONS FOR NURSING PRACTICE: The study's findings can be useful in directing cancer centers' efforts to provide comprehensive care for breast cancer survivors. Nurses play a critical role in leading these efforts for supportive-care services intended to improve the QOL of breast cancer survivors.

Effect of halothane equilibration kinetics on in vitro muscle contractures for malignant hyperthermia screening.

In vitro muscle contracture tests for malignant hyperthermia screening are routinely performed using standardized protocols. In the present study on-line monitoring of halothane concentrations in the gas phase was demonstrated to be an improved test standard. The kinetics of halothane concentration and their effect on in vitro muscle contracture tests were evaluated in two test baths, I and II, which contained 3 and 18 ml Krebs-Ringer solution, respectively. The equilibration kinetics for halothane was significantly faster in bath I (t1/2 = 8.2 s) compared with bath II (t1/2 = 25.6 s). Twenty-one pairs of muscle bundles from 21 potentially malignant hyperthermia susceptible patients were investigated, each test bath receiving one bundle from each pair. The variance of muscle contractures was significantly increased in test bath I compared with test bath II. However, there was no influence on malignant hyperthermia diagnosis, suggesting that, within the ranges of t1/2 = 8.2 s-25.6 s, the test bath volumes need not be standardized.

[Drug therapy knowledge in ambulatory cardiovascular patients]. / Was wissen Herzkreislaufpatienten über ihre Medikamente?

To analyse drug therapy knowledge of prescribed drugs and self-administered medicinal products we interviewed 222 ambulatory cardiovascular patients. Spontaneous mentions of drugs (at least 3 preparations on average) were completed later on specific questioning. 40% of patients once interrupted their therapy due to adverse drug reactions. Most patients knew the labels of their medicaments but the effects and indications only in 50%. Nevertheless 70% were satisfied with the informations of the physician. Drugs available over the counter were consumed in many of the respondents: 50% consumed analgetics, and--mainly female patients--25% sedatives and 15% laxatives or diuretics. We conclude that specific questioning on self-administation of OTC preparations or formerly prescribed drugs results in an improved overview of medication and a better handling of polymedication and drug compliance.

Pharmacokinetics of midazolam in patients recovering from cardiac surgery.

The pharmacokinetics of midazolam has been studied in patients recovering from cardiac surgery, who required sedation for postoperative mechanical ventilation. Twelve males (mean age 64.5 years) with severe heart disease received an infusion of midazolam 15 mg.h-1 for 4 h, starting 1 to 3 h post surgery. Multiple blood samples were collected from each patient during the infusion and up to 48-93 h after it. The pharmacokinetic parameters of midazolam were determined using both moment analysis and the program NONMEM. The average terminal half-life was 10.6 h. The prolonged elimination was mainly due to a decrease in its metabolic clearance (0.25 l.min-1). The maintenance infusion dose of midazolam in such patients should be reduced. The time to recovery after stopping an infusion depends upon the amount of drug in the body at that time and a simulation of the plasma concentrations after various infusion regimens suggests that recovery will be delayed after prolonged (greater than 48 h) administration of midazolam to these patients. However, after shorter infusions (less than 12 h), redistribution of the drug away from the site of action was still occurring and recovery would be expected to be relatively rapid.

Metabolic patterns in various structures of the rat nephron. The distribution of enzymes of carbohydrate metabolism.

By means of the microdissection technique applied on kidney tissue, the following results were obtained: Hexokinase, an enzyme of glycolysis, revealed a low activity in the proximal and a high activity in the distal tubule. This distribution pattern is consistent with the finding that glucose is the main fuel for the distal tubule. Glucose-6-phosphatase, an enzyme of gluconeogenesis, demonstrates a significant activity in the distal tubule and in the glomerulus. Both structures are, however, no glucose producers. Phosphoenolpyruvate carboxykinase, the key enzyme of gluconeogenesis, is found only in the segments of the proximal tubule. The distal tubule lacks any activity. This is also the case during starvation and metabolic acidosis when gluconeogenesis is stimulated. Glutamic dehydrogenase, -an enzyme possibly connected with ammoniagenesis-, malate- and lactate dehydrogenase-, enzymes involved with hydrogen transfer through the mitochondrial membrane-, showed a close parallelism to phosphoenolpyruvate carboxykinase in their distribution along the proximal tubule. The bidirectional function of glyceraldehyde-P dehydrogenase is well documented by the close correlation to phosphoenolpyruvate carboxykinase (gluconeogenesis) in the proximal tubule and to pyruvic kinase (glycolysis) in the distal tubule.

Quality of life in breast cancer survivors as identified by focus groups.

Currently, over 1,700,000 women are living with breast cancer in the United States. These long-term survivors of breast cancer are challenged to redirect their energy from issues of cancer treatment and early side effects toward quality of life issues related to long-term survivorship, such as menopause, infertility, fear of recurrence, family distress, and uncertainty. In an attempt to obtain patient perspectives on quality of life and health care issues faced by breast cancer survivors, focus group methodology was utilized in the first year of a 2 year study. The sample was stratified to represent three age groups: < 40 years, 40-60 years, and > 60, and was intended to represent different developmental levels believed to have varying experiences with quality of life and potentially divergent needs following breast cancer diagnosis. Results of these focus groups revealed unique quality of life concerns of breast cancer survivors across four domains of physical, psychological, social, and spiritual well being. Each of these domains yields important implications for future research and clinical practice.

Determination of the partial pressure of halothane (or isoflurane) in blood.

A gas chromatographic method is described for the direct quantitative determination of the partial pressure of halothane (or isoflurane) in blood as well as the blood-gas partition coefficient. A head space technique and a flame ionization detector were used. Standard blood was obtained by equilibrating patients' blood with known gas concentrations in a tonometer. Using an infra-red analyser to measure the halothane gas concentration in the tonometer and within the anaesthetic system allowed for the direct comparison of the partial pressure in blood to the partial pressure in the inspired gas. Technical problems associated with this procedure, and with comparable methods, are discussed.