Efficacy of nurse telehealth care and peer support in augmenting treatment of depression in primary care.

BACKGROUND: Primary care treatment of depression needs improvement. OBJECTIVE: To evaluate the efficacy of 2 augmentations to antidepressant drug treatment. DESIGN: Randomized trial comparing usual care, telehealth care, and telehealth care plus peer support; assessments were conducted at baseline, 6 weeks, and 6 months. SETTING: Two managed care adult primary care clinics. PARTICIPANTS: A total of 302 patients starting antidepressant drug therapy. INTERVENTIONS: For telehealth care: emotional support and focused behavioral interventions in ten 6-minute calls during 4 months by primary care nurses; and for peer support: telephone and in-person supportive contacts by trained health plan members recovered from depression. MAIN OUTCOME MEASURES: For depression: the Hamilton Depression Rating Scale and the Beck Depression Inventory; and for mental and physical functioning: the SF-12 Mental and Physical Composite Scales and treatment satisfaction. RESULTS: Nurse-based telehealth patients with or without peer support more often experienced 50% improvement on the Hamilton Depression Rating Scale at 6 weeks (50% vs 37%; P =.01) and 6 months (57% vs 38%; P =.003) and on the Beck Depression Inventory at 6 months (48% vs 37%; P =. 05) and greater quantitative reduction in symptom scores on the Hamilton scale at 6 months (10.38 vs 8.12; P =.006). Telehealth care improved mental functioning at 6 weeks (47.07 vs 42.64; P =.004) and treatment satisfaction at 6 weeks (4.41 vs 4.17; P =.004) and 6 months (4.20 vs 3.94; P =.001). Adding peer support to telehealth care did not improve the primary outcomes. CONCLUSION: Nurse telehealth care improves clinical outcomes of antidepressant drug treatment and patient satisfaction and fits well within busy primary care settings.

The never ripe mutant provides evidence that tumor-induced ethylene controls the morphogenesis of agrobacterium tumefaciens-induced crown galls on tomato stems

We confirm the hypothesis that Agrobacterium tumefaciens-induced galls produce ethylene that controls vessel differentiation in the host stem of tomato (Lycopersicon esculentum Mill.). Using an ethylene-insensitive mutant, Never ripe (Nr), and its isogenic wild-type parent we show that infection by A. tumefaciens results in high rates of ethylene evolution from the developing crown galls. Ethylene evolution from isolated internodes carrying galls was up to 50-fold greater than from isolated internodes of control plants when measured 21 and 28 d after infection. Tumor-induced ethylene substantially decreased vessel diameter in the host tissues beside the tumor in wild-type stems but had a very limited effect in the Nr stems. Ethylene promoted the typical unorganized callus shape of the gall, which maximized the tumor surface in wild-type stems, whereas the galls on the Nr stems had a smooth surface. The combination of decreased vessel diameter in the host and increased tumor surface ensured water-supply priority to the growing gall over the host shoot. These results indicate that in addition to the well-defined roles of auxin and cytokinin, there is a critical role for ethylene in determining crown-gall morphogenesis.

SIDS, abnormal nighttime REM sleep and CNS immaturity.

SIDS (Sudden Infant Death Syndrome) is the major cause of death in young, apparently healthy, infants, yet its etiology and pathogenesis remain unknown. SIDS peaks at 2-4 months, is more prevalent in the winter months and typically occurs in the early morning hours when most babies are asleep, suggesting that sleep may be part of the pathophysiological mechanism of SIDS. The sleep patterns of infants at high risk for SIDS were analyzed to test the hypothesis that there are abnormalities specific to nighttime sleep which may be indicative of a central nervous system (CNS) deficit that contributes to a high frequency of SIDS during the night. Electrophysiological sleep variables were recorded at monthly intervals in 1-6 months-old infants during the peak age of SIDS. The risk group (R) was resuscitated from a potentially life-threatening Sudden A-Ventilatory Event (S.A.V.E.) and compared to a group of control infants (C) with no family history of SIDS. The data representing four equal time intervals from 11 p.m.-11 a.m. show an abrupt, statistically significant increase in REM sleep from 2-5 a.m. in R infants. In C infants, time spent in REM sleep after 2 a.m. becomes progressively shorter while NREM sleep is proportionately longer. From 11 p.m.-2 a.m., however, R and C infants do not differ either in the duration or in the percent of total sleep time (TST) of REM sleep. We hypothesize that these REM sleep abnormalities in vulnerable infants are indicative of a pervasive CNS immaturity. The higher prevalence of SIDS in the cold winter months and in the early morning hours, when darkness is prolonged, is discussed in relation to the possible involvement of the circadian rhythm of melatonin.

Health care utilization and outcomes among persons with rheumatoid arthritis in fee-for-service and prepaid group practice settings.

OBJECTIVE: To compare health care utilization and outcomes over an 11-year period among persons with rheumatoid arthritis (RA) in fee-for-service and prepaid group practice settings. DESIGN: Cohort of persons with RA followed up for as long as 11 years. The principal measures were obtained from an annual structured telephone interview conducted by a trained survey worker. SETTING: Persons with RA presenting to a random sample of community rheumatologists in northern California. PATIENTS: Patients were enrolled in 2 cycles: in 1982 and 1983 and in 1989. Study rheumatologists listed all persons meeting criteria for RA presenting to their offices over a 1-month period. Of the 1062 so listed, we enrolled 1025, or 96.5%. Of the 1025 persons with RA, 227 (22.2%) reported receiving care in prepaid group practice settings. MAIN OUTCOME MEASURES: As of the end of 1994, 5295 person-years of observation were available for the analysis of the annual level of the utilization and outcome measures; 341 persons had been followed up for all 11 years of the study. The main utilization outcomes measured included office visits, outpatient surgeries, hospital admissions, and painful joints. RESULTS: The persons with RA in fee-for-service and prepaid group practice settings did not differ in the quantity of health care used in any 1 year for either RA or non-RA reasons. Among those followed up for all 11 years, the persons in fee-for-service and prepaid group practice settings did not differ in the cumulative quantity of health care used over the entire period of study. The 2 groups did not differ on any outcome measure on either an annual or long-term basis. The results of mortality analyses were inconsistent: using Kaplan-Meier estimates, the persons with RA in prepaid group practice settings survived significantly longer (P<.05 by long-rank test); using Cox proportional hazards methods, the proportion dying each year did not differ signficantly. CONCLUSIONS: We could find no evidence that persons with RA in fee-for-service and prepaid group practice settings received different quantities of health care or experienced different outcomes on either an annual or long-term basis.

An activator of calcium-dependent potassium channels isolated from a medicinal herb.

Large-conductance calcium-dependent potassium (maxi-K) channels play an important role in regulating the tone of airway smooth muscle and the release of bronchoconstrictive substances from nerves in the lung. Crude extracts of Desmodium adscendens, a medicinal herb used in Ghana as a treatment for asthma, inhibit binding of monoiodotyrosine charybdotoxin (125I-ChTX) to receptor sites in bovine tracheal smooth muscle membranes that have been shown to be associated with maxi-K channels. Using this assay, three active components have been purified and identified by NMR and MS. Comparison with authentic samples revealed the three active components as the known triterpenoid glycosides dehydrosoyasaponin I (DHS-I), soyasaponin I, and soyasaponin III. The most potent of these compounds, DHS-I, is a partial inhibitor of 125I-ChTX binding (Ki = 120 nM, 62% maximum inhibition). Inhibition of 125I-ChTX binding is primarily due to a decrease in the observed maximum number of binding sites, with a smaller decrease in affinity. DHS-I increases the rate of toxin dissociation from its receptor, suggesting that modulation of ChTX binding occurs through an allosteric mechanism. DHS-I reversibly increases the open probability of maxi-K channels from bovine tracheal smooth muscle incorporated into planar lipid bilayers when applied to the intracellular, but not the extracellular, side of the membrane at concentrations as low as 10 nM. In contrast, DHS-I had no effect on several other types of potassium channels or membrane transporters. This natural product is the first example of a high-affinity activator of calcium-dependent potassium channels and is the most potent known potassium channel opener.

Characterization of high affinity binding sites for charybdotoxin in synaptic plasma membranes from rat brain. Evidence for a direct association with an inactivating, voltage-dependent, potassium channel.

Charybdotoxin (ChTX), a potent peptidyl inhibitor of several types of K+ channels, binds to sites in vascular smooth muscle sarcolemma (Vázquez, J., Feigenbaum, P., Katz, G. M., King, V. F., Reuben, J. P., Roy-Contancin, L., Slaughter, R. S., Kaczorowski, G. J., and Garcia, M. L. (1989) J. Biol. Chem. 265, 20902-20909) which are functionally associated with a high conductance Ca2(+)-activated K+ channel (PK,Ca). 125I-ChTX also binds specifically and reversibly to a single class of sites in plasma membranes prepared from rat brain synaptosomes. These sites exhibit a Kd of 25-30 pM, as measured by either equilibrium or kinetic binding protocols and display a maximum density of about 0.3-0.5 pmol/mg of protein. Competition studies with native ChTX yield a Ki of 8 pM for the noniodinated toxin. The highest density of ChTX sites exists in vesicle fractions of plasma membrane origin. Binding of 125I-ChTX is modulated by metal ions that interact with K+ channels: Ba2+, Ca2+, and Cs+ cause inhibition of ChTX binding; Na+ and K+ stimulate binding at low concentration before producing complete inhibition as their concentration is increased. Stimulation of binding is due to an allosteric interaction that decreases Kd whereas inhibition results from an ionic strength effect. Tetraethylammonium ion has no effect on binding, but tetrabutylammonium ion blocks binding with a Ki of 2.5 mM. Different toxins (i.e. alpha-dendrotoxin, noxiustoxin) that inhibit an inactivating, voltage-dependent K+ channel (PK,V) block 125I-ChTX binding in brain. In marked contrast, iberiotoxin, a selective inhibitor of PK,Ca, has no effect on ChTX binding in this preparation. Inhibition of ChTX binding by alpha-dendrotoxin and noxiustoxin results from an allosteric interaction between separate binding sites for these agents and the ChTX receptor. Taken together, these results suggest that the ChTX sites present in brain are associated with PK,V rather than with PK,Ca. Therefore, 125I-ChTX is a useful probe for elucidating the biochemical properties of a number of different types of K+ channels.

Purification and characterization of a unique, potent, peptidyl probe for the high conductance calcium-activated potassium channel from venom of the scorpion Buthus tamulus.

An inhibitor of the high conductance, Ca2(+)-activated K+ channel (PK,Ca) has been purified to homogeneity from venom of the scorpion Buthus tamulus by a combination of ion exchange and reversed-phase chromatography. This peptide, which has been named iberiotoxin (IbTX), is one of two minor components of the crude venom which blocks PK,Ca. IbTX consists of a single 4.3-kDa polypeptide chain, as determined by polyacrylamide gel electrophoresis, analysis of amino acid composition, and Edman degradation. Its complete amino acid sequence has been defined. IbTX displays 68% sequence homology with charybdotoxin (ChTX), another scorpion-derived peptidyl inhibitor of PK,Ca, and, like this latter toxin, its amino terminus contains a pyroglutamic acid residue. However, IbTX possesses 4 more acidic and 1 less basic amino acid residue than does ChTX, making this toxin much less positively charged than the other peptide. In single channel recordings, IbTX reversibly blocks PK,Ca in excised membrane patches from bovine aortic smooth muscle. It acts exclusively at the outer face of the channel and functions with an IC50 of about 250 pM. Block of channel activity appears distinct from that of ChTX since IbTX decreases both the probability of channel opening as well as the channel mean open time. IbTX is a selective inhibitor of PK,Ca; it does not block other types of voltage-dependent ion channels, especially other types of K+ channels that are sensitive to inhibition by ChTX. IbTX is a partial inhibitor of 125I-ChTX binding in bovine aortic sarcolemmal membrane vesicles (Ki = 250 pM). The maximal extent of inhibition that occurs is modulated by K+, decreasing as K+ concentration is raised, but K+ does not affect the absolute inhibitory potency of IbTX. A Scatchard analysis indicates that IbTX functions as a noncompetitive inhibitor of ChTX binding. Taken together, these data suggest that IbTX interacts at a distinct site on the channel and modulates ChTX binding by an allosteric mechanism. Therefore, IbTX defines a new class of peptidyl inhibitor of PK,Ca with unique properties that make it useful for investigating the characteristics of this channel in target tissues.

Characterization of high affinity binding sites for charybdotoxin in sarcolemmal membranes from bovine aortic smooth muscle. Evidence for a direct association with the high conductance calcium-activated potassium channel.

Charybdotoxin (ChTX), a peptidyl inhibitor of the high conductance Ca2+-activated K+ channel (PK,Ca), has been radiolabeled to high specific activity with 125I, and resulting derivatives have been well separated. The monoiodotyrosine adduct blocks PK,Ca in vascular smooth muscle with slightly reduced potency compared with the native peptide under defined experimental conditions. [125I]ChTX, representing this derivative, binds specifically and reversibly to a single class of sites in sarcolemmal membrane vesicles prepared from bovine aortic smooth muscle. These sites display a Kd of 100 pM for the iodinated toxin, as determined by either equilibrium or kinetic binding analyses. Binding site density is about 500 fmol/mg of protein in isolated membranes. The addition of low digitonin concentrations to disrupt the vesicle permeability barrier increases the maximum receptor concentration to 1.5 pmol/mg of protein, correlating with the observations that ChTX binds only at the external pore of PK,Ca and that the membrane preparation is of mixed polarity. Competition studies with ChTX yield a Ki of about 20 pM for native toxin. Binding of [125I]ChTX is modulated by ionic strength as well as by metal ions that are known to interact with PK,Ca. Moreover, tetraethylammonium ion, which blocks PK,Ca with moderately high affinity when applied at the external membrane surface, inhibits [125I]ChTX binding in an apparently competitive fashion with a Ki similar to that found for channel inhibition. In marked contrast, agents that do not inhibit PK,Ca in smooth muscle (e.g. tetrabutylammonium ion, other toxins homologous with ChTX, and pharmacological agents that modulate the activity of dissimilar ion channels) have no effect on [125I]ChTX binding in this tissue. Taken together, these results suggest that the binding sites for ChTX which are present in vascular smooth muscle are directly associated with PK,Ca, thus identifying [125I]ChTX as a useful probe for elucidating the biochemical properties of these channels.

Evidence for distinct sites coupled to high affinity omega-conotoxin receptors in rat brain synaptic plasma membrane vesicles.

The neuronal Ca2+ channel blocker omega-conotoxin (GVIA) binds with very high affinity (Kd of 0.8 pM) to a single class of receptors in purified rat brain synaptic plasma membrane vesicles. Three types of agents have been found to modulate toxin binding. The affinity of omega-conotoxin is decreased by metal ions or organic cations which interact at the pore of voltage-dependent Ca2+ channels. Dynorphin A [1-13] and related peptides stimulate omega-conotoxin binding by increasing toxin affinity through a nonopiate allosteric mechanism. Venom of the spider Plectreurys tristes inhibits omega-conotoxin binding (IC50 of 30 ng protein/ml) by a noncompetitive allosteric mechanism. These results suggest that omega-conotoxin binding sites exist in a complex with distinct receptors for other agents, all of which may be functionally associated with neuronal Ca2+ channels.

A comparison of lay-taught and professional-taught arthritis self-management courses.

One hundred subjects with arthritis were randomized into lay-taught, or professional-taught 12-h arthritis self-management courses, or a control group. Outcomes, knowledge, exercise, relaxation, disability, pain, and number of physician visits were measured aat baseline and 4 months. Professional-taught groups demonstrated greater knowledge gain while lay-taught groups had greater changes in relaxation (p less than .01) and a tendency toward less disability. Although it is impossible to draw definitive conclusions, this study suggests that lay leaders can teach arthritis self-management courses with results similar to those achieved by professionals.

Pipecolic acid antagonizes barbiturate-enhanced GABA binding to bovine brain membranes.

L-Pipecolic acid, a brain L-lysine metabolite, is found to inhibit GABA binding to bovine synaptic membranes strongly in the presence of hexobarbital (IC50 = 2 X 10(-10)M) or pentobarbital (IC50 = 2 X 10(-9)M), but only slightly (less than 10%) by itself. Longer dialysis increases this binding inhibition. Hill plots indicate heterogeneity of L-pipecolic acid displaceable GABA binding sites. L-Pipecolic acid may be an endogenous ligand acting as a neuromodulator on the GABA receptor ionophore complex, or it may act on its own membrane binding sites exerting an allosteric effect on the GABA receptor complex. This discovery may be useful for further defining pharmacological and biochemical differences between the GABA receptors in the brain.

Regulation of muscarinic cholinergic receptor density in neuroblastoma cells by brief exposure to agonist: possible involvement in desensitization of receptor function.

Cell membrane surface muscarinic receptors on mouse neuroblastoma cells (clone N1E-115) are subject to a rapid receptor-mediated regulation upon contact with receptor agonists. Pretreatment of cells for 30 min at 37 degrees C resulted in a significant reduction in the specific binding of the hydrophilic ligand N-[3H] methylscopolamine. The magnitude of the reduction was dependent on agonist concentration and temperature. This phenomenon also demonstrated saturability. Further characterization of this reduced binding revealed that it is a "true" disappearance of the cell membrane surface receptors and that receptor activation is needed to trigger this receptor regulation. Once the agonist was removed, almost complete recovery of the cell membrane surface receptors was seen within 30 min at 37 degrees C. A number of similarities have been demonstrated to exist between agonist-induced desensitization of receptor-mediated increase in cyclic GMP formation and agonist-induced receptor regulation, which suggests that both phenomena might be related.

Regulatory effect of cytokinin on secondary xylem fiber formation in an in vivo system.

The regulatory effect of cytokinin on the formation of secondary xylem fibers was studied in the hypocotyl of young Helianthus annuus L. plants. Positive correlation was found between the kinetin supplied (0.25-0.5 micrograms/gram) to the growth medium and the rate of fiber formation within and between the vascular bundles. Reducing the root originated cytokinin supply, either by root removal or by lowering the transpiration rate, diminished the number of newly formed secondary xylem fibers. This decrease was considerably reversed in the presence of 0.5 microgram/gram kinetin. Early pulse exposure of kinetin had a temporary promoting effect on fiber differentiation at low concentrations and a permanent inhibitory effect at high concentration.

A controlled trial of antihypertensive therapy in systemic sclerosis (scleroderma).

Antihypertensive treatment may be life saving in scleroderma renal crisis. Patients surviving such crises frequently have had dramatic improvement in the dermal manifestations of their scleroderma. To investigate the potential role of antihypertensive treatment in nonhypertensive patients we randomly assigned 28 patients with systemic sclerosis into drug (14) and placebo (14) groups, using blocked randomisation , and followed them up in a prospective, double-blind clinical trial for 24 months. Overall, both groups improved slightly, with both subjective and objective markers. There were no statistically significant differences and no clinically meaningful trends between the 2 groups, except that the blood pressure was reduced in the group on the active drug.

Short-term regulation of muscarinic acetylcholine receptor binding in cultured nerve cells.

Short-term preincubation of mouse neuroblastoma cells (clone N1E-115) with the muscarinic agonist carbamylcholine at 37 degrees C resulted in a significant decrease in the binding of the muscarinic antagonist [3H]N-methylscopolamine. This agonist-induced response reached a steady state at 30 min. It was also dose dependent, saturable and sensitive to temperature, suggesting a receptor-mediated phenomenon. The significance of these findings is discussed.

The variability of immunologic laboratory tests.

To determine the clinical reliability of certain immunologic tests, serum complement (C3), DNA binding (DNAB), and fluorescent antinuclear antibody (FANA) were measured blindly at 2 university immunology laboratories on duplicate serum samples from 667 patients with connective tissue diseases. Twenty-seven percent of patients were differently classified as normal or abnormal for C3 by the 2 laboratories. The mean of paired differences was 25 mg% and large variability remained even after adjustment. Repeat assays on a random subset of 91 sera showed persistent variability. Fifteen percent of patients were differently classified by their DNAB results in 11% by FANA tests. Considering this variability, these "objective" laboratory tests alone are not sufficiently reliable for accurately defining diseases or disease activity.