SEARCH · Search PubMed

Results for “confidence limits”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources

PubMed1989

The pharmacokinetics and toxicity of the anthrapyrazole anti-cancer drug CI-941 in the mouse: a guide for rational dose escalation in patients.

CI-941 is a new synthetic DNA-binding agent selected for phase I clinical evaluation. The drug has broad-spectrum antitumour activity against a number of murine tumours and, in contrast to doxorubicin, is unlikely to induce cardiotoxicity by a free-radical-mediated mechanism. In this study the toxicity and pharmacokinetics of CI-941 were studied in the mouse to enable the implementation of a pharmacokinetically guided dose-escalation strategy in patients. Following a single i.v. bolus injection in mice, CI-941 induced dose-dependent leukopenia. The white blood cell counts were suppressed on day 3 by 18%, 50% and 65% of control, at doses of 10, 15 and 20 mg/kg CI-941, respectively. Other toxicities such as weight loss, alopecia, diarrhoea and convulsions were observed at doses greater than 20 mg/kg. Lethality studies in female Balb-c mice resulted in an LD10 value of 20 mg/kg (95% confidence limits; range, 19-21 mg/kg) and an LD50 value of 22 mg/kg (95% confidence limits; range, 21-23 mg/kg). The pharmacokinetics of CI-941 were studied at four dose levels from 1/10 of the LD10 to the LD10 (20 mg/kg). The drug was rapidly cleared from the plasma (250-400 ml/min per kg) at a rate approaching the cardiac output of mice, displaying triphasic plasma pharmacokinetics. The area under the plasma CI-941 concentration vs time curve (AUC) was linear with respect to the dose, up to and including 15 mg/kg (AUC = 110 microM x min at 15 mg/kg), but became non-linear at 20 mg/kg (AUC = 277 microM x min). Despite 80%-84% plasma protein binding, CI-941 was rapidly and extensively distributed into tissues, especially the kidney. Following i.v. bolus injections at doses of 1.5 and 15 mg/kg, elimination of the parent compound by urinary excretion accounted for 12%-18% of the delivered dose. A phase-I starting dose (based on that equivalent to 1/10 of the LD10 in the mouse) of 5 mg/m2 CI-941 is recommended for single administration schedules. In addition, a pharmacokinetically guided dose-escalation strategy, based on achieving a target AUC of 110 microM x min, is proposed.

Animals↗

PubMed1992

Internal rectal intussusception: results of surgical repair.

Twenty-four patients with obstructed defecation due to rectal intussusception diagnosed by defecography were treated with rectopexy either by the Wells technique (9 patients) or by Orr's operation (15 patients). After follow-up from one to eight years, defecography demonstrated disappearance of the intussusception in 22 patients. None of the patients were completely relieved of their symptoms. Nine (41 percent; 95 percent confidence limits: 21-64) were improved and 13 were unchanged (59 percent; 95 percent confidence limits: 36-79), with no difference between the two procedures. One patient with solitary rectal ulcer was improved, and the ulcer disappeared. Four patients with moderate preoperative incontinence became continent postoperatively, but obstructed defecation was only improved in two of these patients. It is concluded that rectal intussusception is probably a secondary phenomenon in patients with obstructed defecation and that a conservative attitude toward surgery should be adopted.

Adult↗

PubMed1997

Childhood size is more strongly related than size at birth to glucose and insulin levels in 10-11-year-old children.

In adults low birthweight and thinness at birth are associated with increased risk of glucose intolerance and non-insulin-dependent diabetes mellitus. We have examined the relations between size at birth (birthweight, thinness at birth) and levels of plasma glucose and serum insulin in children, and compared them with the effects of childhood size. We performed a school-based survey of 10-11-year-old British children (response rate 64%) with measurements made after an overnight fast. One group of children (n = 591) was studied fasting while the other (n = 547) was studied 30 min after a standard oral glucose load (1.75 g/kg). Serum insulin was measured by a highly specific ELISA method. Birthweight was assessed by maternal recall and thinness at birth using birth records. Neither fasting nor post-load glucose levels showed any consistent relationship with birthweight or ponderal index at birth. After adjustment for childhood height and ponderal index, both fasting and post-load insulin levels fell with increasing birthweight. For each kg increase in birthweight, fasting insulin fell by 16.9% (95% confidence limits 7.1-25.8%, p = 0.001) and post-load insulin by 11.6% (95% confidence limits 3.5-19.1%, p = 0.007). However, the proportional change in insulin level for a 1 SD increase in childhood ponderal index was much greater than that for birthweight (27.2% and -8.8%, respectively, for fasting insulin). We conclude that low birthweight is not related to glucose intolerance at 10-11 years, but may be related to the early development of insulin resistance. However, in contemporary children obesity is a stronger determinant of insulin level and insulin resistance than size at birth.

Adult↗

PubMed1992

A comparison of ovulation suppression and ovulation stimulation in the treatment of endometriosis-associated infertility.

This study compares ovulation stimulation or suppression with the pregnancy rate among infertile couples with endometriosis. The design is a nonrandomized, prospective, multicentered cohort analytic study. Two hundred and ninety-seven couples with laparoscopy-proven endometriosis were analyzed: 68 received no therapy, 42 received clomiphene and 74 received danazol. Forty patients (22%) conceived and pregnancy rates were similar in each treatment group. The relative likelihood of pregnancy associated with clomiphene was 2.9 (95% confidence limits 1.2-7.1); the relative likelihood of pregnancy with danazol was 1.02 (95% confidence limits 0.5-2.3). This study suggests that pregnancy rates during clomiphene treatment could be superior to expectant therapy, while pregnancy rate after danazol is similar to no treatment.

Adult↗

PubMed1996

Acute and chronic effects of potassium and noradrenaline on Na+, K+-ATPase activity in cultured mouse neurons and astrocytes.

Acute and chronic effects of elevated extracellular concentrations of potassium ions ([K+]0) and/or noradrenaline were studied in homogenates of primary cultures of mouse astrocytes, from the cerebral cortex or the spinal cord, and of primary cultures of mouse cerebral cortical neurons. NA+, K+-ATPase activity in cerebral cortical astrocytes showed a Km value of 1.9 mM with confidence limits of 1.3-2.9 mM and a Vmax of 5.4 mumol/h/mg protein with confidence limits of 3.3-8.1 mumol/h/mg protein. Due to the high Km value, the activity of the enzyme was significantly increased by an increase in [K+]0 in the interval 5-12 mM. In cerebral cortical neurons, Vmax was lower (1.77 +/- 0.06 mumol/h/mg protein) but the affinity was higher (Km 0.43 +/- 0.8 mM). With these kinetics, there is no stimulation of enzyme activity when [K+]0 is increased beyond control levels. In spinal cord astrocytes, the relative effect of increasing [K+]0 above 6 mM was larger than in cerebral astrocytes but the absolute activity of the enzyme was lower. Na+, K+-ATPase activity in both types of astrocyte was stimulated by noradrenaline and its beta-adrenergic subtype agonist isoproterenol but mainly or exclusively at 6 mM [K+]0. Noradrenaline also caused a stimulation in cortical neurons, but at non-physiological K+ concentrations this stimulation was converted to an inhibition, and isoproterenol had no stimulatory effect. Chronic exposure of cerebral cortical astrocytes to elevated [K+]0 caused a decrease in Na+, K+-ATPase activity when enzyme activity in the cells was subsequently measured at normal [K+]0. During exposure to 30 mM [K+]0 this "down-regulation" took place within 10 min. Conversely, chronic exposure to reduced [K+]0 led to an increase in Na+, K+-ATPase activity. Chronic exposure to noradrenaline had no significant effect but there was a tendency towards an increase.

Adrenergic alpha-Agonists↗

PubMed2004

Graphical enhancement to support PCA-based process monitoring and fault diagnosis.

Principal component analysis (PCA) for process modeling and multivariate statistical techniques for monitoring, fault detection, and diagnosis are becoming more common in published research, but are still underutilized in practice. This paper summarizes an in-depth case study on a chemical process with 20 monitored process variables, one of which reflects product quality. The analysis is performed using the PLS_Toolbox 2.01 with MATLAB, augmented with software which automates the analysis and implements a statistical enhancement that uses confidence limits on the residuals of each variable for fault detection rather than just confidence limits on an overall residual. The newly developed graphical interface identifies and displays each variable's contribution to the faulty behavior of the process; and it aids greatly in analyzing results. The case study analyzed within shows that using the statistical enhancement can reduce the fault detection time, and the automated graphical interface implements the enhancement easily.

Artificial Intelligence↗

PubMed1998

Evaluation of mutant frequencies at the hprt and the T-cell receptor loci in pediatric cancer patients before treatment.

Mutant frequencies (Mfs) at the two genetic loci, the hypoxanthine phosphoribosyl transferase (hprt) gene and the T-cell receptor (TCR) gene were evaluated in pediatric cancer patients before starting chemotherapy or radiotherapy. The study population consisted of 27 patients with various solid tumors (mean age +/- SD; 5.5 +/- 5.1 years, range; 0.2-14.5 years), 5 patients with acute leukemia (10.3 +/- 6.1, 1.3-17.0 years), and 26 healthy controls (11.6 +/- 4.0, 4.4-22.2 years). Although the age distributions were different, the mean Mf values of the hprt and the TCR loci were comparable among these three groups. On an individual basis taking the age factor into consideration, the hprt-Mfs of 3 patients with solid tumors, i.e., two patients with Hodgkin's disease and one patient with Askin tumor, were found to be well above the 95% confidence limit. There were no patients with a TCR-Mf exceeding the 95% confidence limit. These data suggest the possibility that some patients with solid tumors may be predisposed to mutational susceptibility before treatment. The assay of the hprt-Mf appears more sensitive than the TCR-Mf assay in distinguishing these patients.

Adolescent↗

PubMed1991

Verification of endotracheal tube placement with colorimetric end-tidal CO2 detection.

STUDY OBJECTIVE: To determine the ability of a disposable colorimetric CO2 detector to accurately confirm or refute endotracheal tube placement. DESIGN: Two hundred fifty prospective emergency intubations. SETTING: Emergency intubations performed in the emergency department, helicopter, and prehospital ground environment. TYPE OF PARTICIPANTS: Intubations were performed by emergency medicine residents, paramedics, and flight nurses. INTERVENTIONS: The FEF CO2 detector was applied after 250 emergency intubations. Notation of color change indicating intratracheal placement was recorded in each case. Confirmation of refutation of the detector's results was determined subsequently through traditional methods. RESULTS: The sensitivity for confirmation of endotracheal intubation in the 137 patients with a palpable pulse was 100%. However, only 76 of 103 patients (sensitivity, 72%) in cardiac arrest had endotracheal intubation confirmed by color change. The device was uniformly specific for tracheal intubation in 73 arrested patients in whom a color change was noted (100%). There was one instance (of a total of seven misintubations) in which a positive color change was noted, but the tube was not intratracheal (specificity, 86%). Overall sensitivity for tracheal intubation was 88% (95% confidence limits; range, 0.83 to 0.92), and specificity for tracheal intubation was 92% (95% confidence limits; range, 0.62 to 0.99). CONCLUSION: The FEF colorimetric detector reliably detects intratracheal placement in the nonarrested patient. Its use in prolonged cardiac arrest merits further study.

Breath Tests↗

PubMed1980

Activity of sulfur-containing intermediate metabolites of spironolactone.

The renal antimineralocorticoid activity of single administration of 2 sulfur-containing compounds, which are thought to be intermediate metabolites of spironolactone, was assessed in healthy subjects. They were each active in reversing the urinary electrolyte changes indiced by fludrocortisone for 2 to 10 hr after dosing, but only the 7 alpha-thiomethyl derivative exhibited activity in the period 12 to 16 hr after treatment. The activity of both drugs was less than of spironolactone. Taking urinary log 10 Na/K as the best index of antimineralocorticoid activity, the potencies of the intermediates relative to spironolactone were 0.26 (95% confidence limits, 0.12 to 0.49) for 7 alpha-thio-spirolactone and 0.33 (95% confidence limits, 0.15 to 0.62) for 7 alpha-thiomethyl-spirolactone in the period 2 to 10 hr after medication. We conclude that these minor sulfur-containing intermediate metabolites of spironolactone are unlikely to contribute significantly to the renal antimineralocorticoid activity of spironolactone.

Adult↗

PubMed1988

An assessment of methacholine inhalation tests in elderly asthmatics.

We have assessed the feasibility and value of measuring nonspecific bronchial responsiveness to methacholine in investigation of asthma in the elderly. Results from duplicated tests in 20 subjects aged 65-82 years were expressed as dose provoking a 20% decrement in 1 second forced expiratory volume (PD20.FEV1) or peak expiratory flow (PD20.PEF). Repeatability for PD20.FEV1 was satisfactory but less good than in younger subjects, 95% confidence limits being 0.39-2.57 and 0.52-1.91, respectively, x initial PD20. For PD20.PEF, confidence limits were wider (0.26-3.91 x initial PD20) but multiple PEF measurements were better tolerated than those of FEV1, which commonly caused fatigue and dizziness. PD20.FEV1 and PD20.PEF correlated closely (r = 0.95, P less than 0.0001) and both predicted bronchodilatation following a 6-week course of inhaled corticosteroid and beta agonist. This was not predicted by the response to a single dose of beta agonist. We conclude that measurement of bronchial responsiveness is feasible and clinically valuable in elderly subjects.

Aged↗

PubMed1986

Serum retinol and retinol-binding protein levels do not predict subsequent lung cancer.

Retinol and retinol-binding protein levels were measured in sera previously obtained, and stored in the frozen state, at multiphasic health checkups from 151 persons subsequently found to have lung cancer (cases) and 302 persons who remained free of cancer (controls). Two controls were matched to each case for sex, skin color, age, date of multiphasic health checkup, and aspects of the smoking habit. Mean levels in cases and controls were, respectively, retinol: 82.17 and 82.37 micrograms/dl (p = 0.93), and retinol-binding protein: 6.04 and 6.00 mg/dl (p = 0.81). Mean differences between cases and controls were, retinol: 0.195 micrograms/dl with 95% confidence limits, -3.91 and 4.30 micrograms/dl; retinol-binding protein: -0.033 mg/dl with 95% confidence limits, -0.31 and 0.24 mg/dl. No significant trend in relative risk of lung cancer was observed when the retinol or retinol-binding protein distribution was divided into quintiles. No significant associations were observed in subgroups based on age, sex, histologic type of cancer, cigarette consumption, or interval between blood drawing and cancer diagnosis. In this large study, retinol and retinol-binding protein levels were not useful in predicting the subsequent development of lung cancer.

Adult↗

PubMed1986

Time course of long-term placebo therapy effects in angina pectoris.

A cohort of thirty-five patients with angina pectoris were followed-up for six months with placebo as the only anti-anginal treatment apart from short-acting nitroglycerin. Only patients with at least five attacks per week were entered into the study. Prior to the study, their average number of attacks per week was 10.3(+/- 0.9) and their average nitroglycerin tablet consumption per week was 10.6(+/- 1.2). After admission into the study, the individual dosage of placebo could be blindly titrated during the first eight weeks. Once an adequate dosage was found, it was continued for 6 months. The primary end-point was predefined success or failure of the placebo treatment. Failure was assessed on the lack of improvement, occurrence of 'side-effects', or need for other anti-anginal treatment. In 27 patients, the placebo treatment was said to be a success (95% confidence limits of the percentage of success: 60-90%). No severe cardiac event occurred (confidence limits: 0-10%). Six patients developed 'side-effects'. The number of attacks per week decreased by 48% (P less than 0.0001) during the titration period (8 weeks) and by 77% during the whole 6 months. Exercise test improved, however, less markedly.

Adult↗

PubMed2004

Does malignant hematopoietic disease result from internal exposure to 239Pu?

Neither Fisher's Exact Test nor linear regression analysis (dose-response relationship) using average skeletal dose from 239Pu as a surrogate for marrow dose could establish a statistically significant association between malignant hematopoietic disease (MHD including leukemia and aleukemia) and exposure to 239Pu among dogs in the Utah beagle colony. In addition, when dog-years at risk was the parameter used to estimate the rate of expected malignant hematopoietic tumors in dogs exposed to 239Pu, the estimate was within the range of the 95% confidence limits of the control dogs for six cases (and also within the 95% confidence limits for five cases when the single case of lymphoma was omitted). It was concluded that if there was an effect of 239Pu exposure on the occurrence of MHD in this beagle experiment, it was not very meaningful. These data could not establish a significant susceptibility to neoplasia of either myeloid or lymphoid tissue of 239Pu exposure.

Age Distribution↗

PubMed2001

Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin.

Cytochrome P450 (CYP) 2C9 is the principal enzyme responsible for the metabolism of numerous clinically important drugs. Two polymorphic alleles CYP2C9*2 and CYP2C9*3 have been documented which affect the metabolism and clinical toxicity of drugs such as phenytoin, warfarin, glipizide, and tolbutamide. The present study reports the first example of a null polymorphism in CYP2C9. This mutation dramatically affects the half-life and clinical toxicity of phenytoin. The study subject was a female African-American presented to the emergency department with phenytoin toxicity evidenced by mental confusion, slurred speech, memory loss and the inability to stand. She exhibited extremely poor clearance of phenytoin with an elimination half-life of approximately 13 days. Genotyping studies demonstrated that the patient did not possess any known variant CYP2C9 alleles. Phenytoin is metabolized to a minor extent by the polymorphic CYP2C19, but this individual did not possess any variant CYP2C19 alleles. Sequencing studies revealed that the individual was homozygous for a new CYP2C9 allele (CYP2C9*6) with the deletion of an adenine at base pair 818 of the cDNA. The clearance of phenytoin in this individual is estimated to be approximately 17% of that observed in normal patients. The frequency of this allele was 0.6% (95% confidence limits of 0.1 to 3.5%) in 79 African-Americans and 0% (95% confidence limits of 0 to 1.1%) in 172 Caucasians. The study also demonstrates the severe clinical consequences to patients with a null mutation in CYP2C9 after treatment with normal doses of phenytoin.

Administration, Oral↗

PubMed1984

Assessment of left ventricular filling pressure in myocardial infarction using the first derivative of the apexcardiogram.

We recorded the apexcardiogram (ACG) and its first derivative (dA/dt) in 24 patients with acute or recent myocardial infarction. From dA/dt, an index I = X 10 dRFW/dS was defined (dRFW and dS = peaks of dA/dt corresponding to the rapid filling wave and to the systolic upstroke of the ACG). A significant correlation was found between I and pulmonary capillary wedge pressure (PCW, mmHg). PCW = 2.3 X I + 6.5 (r = 0.80, p less than 0.001). Normal PCW was found in 15 patients who all had an I less than 2.8. Elevated PCW was found in 9 patients who all had an I greater than 2.8. Thus the ability of I to predict elevated PCW was 100% (95% confidence limit greater than 66.4%). The ability to predict normal PCW was 100% (95% confidence limit greater than 76.2%). No significant correlation was found between I and cardiac index (r = 0.29, p greater than 0.1).

Adult↗

PubMed2000

Reliability and validity of a new five-level triage instrument.

OBJECTIVES: Triage is the initial clinical sorting process in hospital emergency departments (EDs). Because of poor reproducibility and validity of three-level triage, the authors developed and validated a new five-level triage instrument, the Emergency Severity Index (ESI). The study objectives were: 1) to validate the triage instrument against ED patients' clinical resource and hospitalization needs, and 2) to measure the interrater reliability (reproducibility) of the instrument. METHODS: This was a prospective, observational cohort study of a population-based convenience sample of adult patients triaged during 100 hours at two urban referral hospitals. Validation by resource use and hospitalization (criterion standards) and reproducibility by blinded paired triage assignments compared with weighted kappa analysis were assessed. RESULTS: Five hundred thirty-eight patients were enrolled; 45 were excluded due to incomplete evaluations. The resulting cohort of 493 patients was 52% female, was 26% nonwhite, and had a median age of 40 years (range 16-95); overall, 159 (32%) patients were hospitalized. Weighted kappa for triage assignment was 0.80 (95% CI = 0.76 to 0.84). Resource use and hospitalization rates were strongly associated with triage level. For patients in category 5, only one-fourth (17/67) required any diagnostic test or procedure, and none were hospitalized (upper confidence limit, 5%). Conversely, in category 1, one of twelve patients was discharged (upper confidence limit, 25%), and none required fewer than two resources. CONCLUSIONS: This five-level triage instrument was shown to be both valid and reliable in the authors' practice settings. It reproducibly triages patients into five distinct strata, from very high hospitalization/resource intensity to very low hospitalization/resource intensity.

Adolescent↗

PubMed1978

Variations of serum testosterone estradiol binding globulin (TeBG) binding capacity in infants during the first year of life.

Serum TeBG binding capacity was measured in 8 cord blood samples, and in peripheral venous blood from 39 male and 31 female infants aged from 1 day to 1 year. In cord blood, TeBG binding capacities were low (1.27 +/- 0.3 microgram/100 ml) with no sex difference. In male infants, TeBG binding capacities increased progressively from birth to 3 months, before decreasing to reach the normal prepubertal level at 6 months. Individual values ranged between 1.16 and 14.5 microgram/100 ml and were significantly correlated with plasma testosterone (r = 0.671, 95% confidence limits 0.440 to 0.818, p less than 0.005) and estradiol (r = 0.734, 95% confidence limits 0.121 to 0.942, p less than 0.01) levels. In female infants, individual values ranged between 1.17 and 14.5 microgram/100 ml, without correlation with age or plasma estradiol level. In male infants the data suggest a positive control ot TeGB binding capacity by estrogens, the negative effect of testosterone being delayed until after the 3rd month of age. In girls, the lack of correlation between TeBG and estradiol can probably be explained by rapid variations of plasma estradiol levels.

Age Factors↗

PubMed1983

Risk of early death in extremely overweight young men.

The effect of pronounced obesity in youth on later mortality was studied in 1239 men with extreme overweight, defined as a weight/height 2 greater than or equal to 31 kg/m2, in the population of 331 919 men liable for military service in the Copenhagen area during the period 1943-1977. A random sample of 2948 drawn from the remaining study population served as a control group. All men were followed up until November 1980, by which time 33 deaths had occurred among the extremely overweight subjects compared with 89 in the control group. This gave a mortality ratio (observed to expected number of deaths) of 1.14 (95% confidence limit 0.91-1.40) for controls with a significantly greater mortality of 1.73 (95% confidence limit 1.20-2.41) for obese subjects. The relative risk, estimated from the survival time distributions, was fairly constant around 1.6 throughout the 37 years of observation. Taking into account age at and year of entry in a regression analysis did not change the relative mortality risk. The proportion of natural death was significantly higher in the obese group than in the control group until the age of 30 but not thereafter. Pronounced obesity in youth is a health hazard, manifesting itself particularly in a distinct increase in mortality from natural causes in early adulthood.

Adolescent↗