The SSTARS (STeroids and Stents Against Re-Stenosis) Trial: Different stent alloys and the use of peri-procedural oral corticosteroids to prevent in-segment restenosis after percutaneous coronary intervention.

BACKGROUND: Stent design and technological modifications to allow for anti-proliferative drug elution influence restenosis rates following percutaneous coronary intervention (PCI). We aimed to investigate whether peri-procedural administration of corticosteroids or the use of thinner strut cobalt alloy stents would reduce rates of binary angiographic restenosis (BAR) after PCI. METHODS: This was a two centre, mixed single and double blinded, randomised controlled trial using a factorial design. We compared (a) the use of prednisolone to placebo, starting at least six hours pre-PCI and continued for 28days post-PCI, and (b) cobalt chromium (CoCr) to stainless steel (SS) alloy stents, in patients admitted for PCI. The primary end-point was BAR at six months. RESULTS: 315 patients (359 lesions) were randomly assigned to either placebo (n=145) or prednisolone (n=170) and SS (n=160) or CoCr (n=160). The majority (58%) presented with an ACS, 11% had diabetes and 287 (91%) completed angiographic follow up. BAR occurred in 26 cases in the placebo group (19.7%) versus 31 cases in the prednisolone group (20.0%) respectively, p=1.00. For the comparison between SS and CoCr stents, BAR occurred in 32 patients (21.6%) versus 25 patients (18.0%) respectively, p=0.46. CONCLUSION: Our study showed that treating patients with a moderately high dose of prednisolone for 28days following PCI with BMS did not reduce the incidence of BAR. In addition, we showed no significant reduction in 6month restenosis rates with stents composed of CoCr alloy compared to SS (http://www.isrctn.com/ISRCTN05886349).

Evoked cortical activity and speech recognition as a function of the number of simulated cochlear implant channels.

OBJECTIVES: (1) To determine if consonant-vowel-consonant (CVC) syllables [Hillenbrand J, Getty L, Clark M, Wheeler K. Acoustic characteristics of American English vowels. J Acoust Soc Am 1995;97:3099-3111] could be used to evoke cortical far field response patterns in humans, (2) to characterize the effects of cochlear implant-simulated channel number on the perception and physiological detection of these same CVC stimuli, and (3) to define the relationship between perception and the morphology of the physiological responses evoked by these speech stimuli. METHODS: Ten normal hearing monolingual English speaking adults were tested. Unprocessed CVC naturally spoken syllables, containing medial vowels, as well as processed versions (2, 4, 8, 12, and 16 spectral channels) were used for behavioral and physiological testing. RESULTS: (1) CVC stimuli evoked a series of overlapping P1-N1-P2 cortical responses. (2) Amplitude of P1-N1-P2 responses increased as neural conduction time (latency) decreased with increases in the number of spectral channels. Perception of the CVC stimuli improved with increasing number of spectral channels. (3) Coinciding changes in P1-N1-P2 morphology did not significantly correlate with changes in perception. CONCLUSIONS: P1-N1-P2 responses can be recorded using CVC syllables and there is an effect of channel number on the latency and amplitude of these responses, as well as on vowel identification. However, the physiological detection of the acoustic changes does not fully account for the perceptual performance of these same syllables. SIGNIFICANCE: These results provide evidence that it is possible to use vocoded CVC stimuli to learn more about the physiological detection of acoustic changes contained within speech syllables, as well as to explore brain-behavior relationships.

A major role for thalamocortical afferents in serotonergic hallucinogen receptor function in the rat neocortex.

Activation of 5-hydroxytryptamine(2A) (5-HT(2A)) receptors by hallucinogenic drugs is thought to mediate many psychotomimetic effects including changes in affect, cognition and perception. Conversely, blockade of 5-HT(2A) receptors may mediate therapeutic effects of many atypical antidepressant and antipsychotic drugs. The purpose of the present study was to determine the source of subcortical glutamatergic afferents, which would project widely throughout the anterior-posterior axis of the rat brain to the apical dendrites of layer V pyramidal cells of the medial prefrontal cortex, from which serotonin induces transmitter release via activation of 5-HT(2A) receptors. Fiber-sparing chemical lesions of the medial thalamus selectively decreased the frequency of serotonin-induced excitatory postsynaptic currents recorded from layer V pyramidal cells in the prelimbic region of the medial prefrontal cortex by 60%. In contrast, large bilateral lesions of the amygdala did not alter the serotonin response. These thalamic lesions significantly decreased the amount of binding to either mu-opioid or metabotropic glutamate 2/3 receptors in the prelimbic region of the medial prefrontal cortex as expected from previous evidence that these agonists for these receptors suppress serotonin-induced excitatory postsynaptic currents by a presynaptic mechanism. Surprisingly, the amount of specific binding to cortical 5-HT(2A) receptors was significantly increased by the medial thalamic lesions. Thus, these experiments demonstrate that activation of cortical 5-HT(2A) receptors modulates transmitter release from thalamocortical terminals. Unexpectedly, lesioning the thalamocortical terminals also alters 5-HT(2A) receptor binding in the prefrontal cortex. These findings are of interest with respect to understanding therapeutic effects of antidepressant/antipsychotic drugs and the known behavioral effects of thalamic lesions in humans.

National Immunization Survey: the methodology of a vaccination surveillance system.

The National Immunization Survey (NIS) was designed to measure vaccination coverage estimates for the US, the 50 states, and selected urban areas for children ages 19-35 months. The NIS includes a random-digit-dialed telephone survey and a provider record check study. Data are weighted to account for the sample design and to reduce nonresponse and non-coverage biases in order to improve vaccination coverage estimates. Adjustments are made for biases resulting from nonresponse and nontelephone households, and estimation procedures are used to reduce measurement bias. The NIS coverage estimates represent all US children, not just children living in households with telephones. NIS estimates are highly comparable to vaccination estimates derived from the National Health Interview Survey. The NIS allows comparisons between states and urban areas over time and is used to evaluate current and new vaccination strategies.

A performance evaluation system for primary care providers in a community health services program.

A performance evaluation system (PES) serves to motivate employees to provide desired behaviors that achieve organizational objectives. In 1989, Denver Health and Hospital (DHH), a publicly funded, integrated delivery system with a large primary care program, instituted a new PES. This report summarizes performance evaluation results for DHH's community health center program. The evaluation focused on the performance of primary care physicians, midlevel practitioners (i.e., physicians assistants, nurse practitioners, and dentists), over a 4-year study period (1990 to 1993). Category-specific performance ratings were based on a 5-point ordinal scale: unacceptable, expectations not met, meets expectations, exceeds expectations, and outstanding. Performance ratings were analyzed as variables that were dependent on several practice characteristics. Results demonstrated a relationship between performance ratings and specific practice characteristics. Based on the results, limitations of the new PES and implications for designing more effective evaluation systems are discussed.

Distribution and ontogeny of 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid-sensitive and quisqualate-insensitive [3H]glutamate binding sites in the rat brain.

Displacement of [3H]glutamate by 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid and quisqualate (in the presence of saturating concentrations of ionotropic glutamate receptor agonists) was used to characterize optimal ionic conditions, distribution, and the ontogeny of glutamate receptor binding sites in rat brain. Using rat forebrain membranes or receptor autoradiography, optimal 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid-sensitive [3H]glutamate binding was found in the presence of 100 mM bromide ions and in the absence of calcium ions. Under these conditions, [3H]glutamate binding was relatively quisqualate insensitive. In regions of the neonatal (11-day-old) and adult rat brain, this [3H]glutamate binding was highest in forebrain (striatum, cerebral cortex, and hippocampus) and hypothalamus/mid-brain but was lower in the cerebellum, olfactory bulb, and pons/medulla regions. 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid-sensitive and quisqualate-insensitive [3H]glutamate binding was present in the rat forebrain at 1 day of age and gradually increased more than twofold by day 50 (adult). Thus, in the presence of bromide ions and in the absence of calcium ions, [3H]glutamate labels a subpopulation of metabotropic glutamate receptors that are sensitive to 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid but insensitive to quisqualate. Expression of [3H]glutamate binding under these conditions was both regionally and developmentally regulated in rat brain, suggesting that [3H]glutamate is labeling a distinct population of metabotropic glutamate receptors.

The long-term effects of metoprolol and epanolol on tissue-type plasminogen activator and plasminogen activator inhibitor 1 in patients with ischaemic heart disease.

This double-blind, randomized parallel group study investigated the effect of 6 months beta-adrenoceptor antagonist therapy with either metoprolol (beta 1-selective without intrinsic sympathomimetic activity [ISA]) or epanolol (beta 1-selective with ISA) on markers of endogenous fibrinolysis in 20 patients with chronic stable angina receiving concurrent treatment with nifedipine. Neither drug had an effect on tissue-type plasminogen activator or plasminogen activator inhibitor type 1 (PAI-1). A significant correlation between fasting insulin and PAI-1 has previously been described and was confirmed in this study. The group treated with metoprolol showed a significant rise in fasting insulin after 6 months with no change in PAI-1. This suggests that the previously described link between these two may not be causal.

A prospective crossover trial of direct current electrotherapy in symptomatic hemorrhoidal disease.

Many new modalities have been developed to treat symptomatic hemorrhoidal disease. In order to determine whether direct current electrotherapy therapy is effective, a prospective, crossover study was done. Sixteen patients referred for treatment of symptomatic hemorrhoids underwent a 16-week treatment protocol. Patients were randomized to receive either medical therapy with a sham therapy, or medical therapy with active direct current electrotherapy at 4-week intervals. All patients were instructed in medical therapy including sitz baths, hydrocortisone suppositories, topical preparations, and a high fiber diet with an educational booklet. Patients who did not respond to initial therapy were crossed over at 8 weeks, receiving alternate therapy twice. Improvement in symptoms, or lack thereof, was not statistically different between the two treatment groups. Comparisons of the internal sphincter pressure, external sphincter pressure, maximum squeeze pressure, and rectal sensitivity to balloon insufflation (volume) were not statistically different before, during, or after any treatment modality (p = 0.46, 0.60, 0.33). The size and grade of hemorrhoids on entry into the study had no bearing on the outcome. In a prospective crossover trial, no difference could be found between standard medical therapy and direct current electrotherapy in the treatment of symptomatic-hemorrhoidal disease.

Peripheral parenteral nutrition is no better than enteral nutrition in acute exacerbation of Crohn's disease: a prospective trial.

The use of parenteral nutrition in patients with exacerbation of regional enteritis is controversial, the clinical dictum being bowel rest and nutritional repletion. In order to address this issue, on the short-term at least, a prospective randomized trial compared peripheral parenteral alimentation and elemental feedings for 2 weeks in patients hospitalized with regional enterities. Both groups had significant objective clinical improvement on their respective nutritional supplementation regimens pre- versus posttherapy as assessed by the Crohn's Disease Activity Index (CDAI) (p less than 0.05). However, there was no significant difference in improvement between parenteral versus enteral groups as assessed by the CDAI. Changes in nutritional assessment parameters, including retinol binding protein, nitrogen balance, total lymphocyte count, and transferrin, were related to the quantity of calories consumed rather than the mode of delivery. A positive nitrogen balance was obtained in all patients despite weight loss in the majority. The route of nutrient delivery in acute exacerbation of regional enteritis does not appear to have an impact on the short-term outcome.

Randomized, controlled trial of a 10-day course of amifloxacin versus trimethoprim-sulfamethoxazole in the treatment of acute, uncomplicated urinary tract infection. Amifloxacin Multi-Center Trial Group.

We conducted a randomized controlled trial of orally administered amifloxacin versus trimethoprimsulfamethoxazole (TMP-SMX) as treatments of acute uncomplicated urinary tract infection in women. Amifloxacin at a dosage of 200 mg twice a day appeared as safe and effective as TMP-SMX, but amifloxacin at 400 mg twice a day tended to cause adverse events more frequently than did TMP-SMX.

Monotherapy of mild hypertension with nifedipine.

The effectiveness of nifedipine as first-line monotherapy for mild diastolic hypertension (range: 95 to 105 mm Hg) was tested in this placebo-controlled, double-blind, randomized trial. Fifty-six patients were enrolled and, after titration of the placebo or active drug, they were followed for 12 weeks. Significant declines in the sitting systolic and diastolic pressures of -19 +/- 4 mm Hg (standard error) and -13 +/- 2 mm Hg, respectively, were observed during this follow-up period. Overall, 75 percent of patients receiving active drug had diastolic pressures less than or equal to 90 mm Hg at the last treatment visit. Heart rate was not significantly changed in the sitting position during the treatment period, and the majority of patients (75 percent) showed a response to nifedipine doses of 10 or 20 mg orally three times daily in the capsule form. The levels of the systolic and diastolic pressures at entry were not predictive of the dose of nifedipine required for effective blood pressure control.