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R B Passey

Publications and source records attributed to R B Passey.

At least 19 recordsLinked to original sources

Foundations for validation of quantitative analytical methods in the clinical laboratory.

This article explores federal requirements for validation of analytical methods and available resources. We focus on the contributions of the National Committee for Clinical Laboratory Standards to the problems of method validation. Illustrations are selected from the Committee's EP5-T Evaluation of Precision, EP10-T Preliminary Evaluation of Clinical Chemistry Methods, EP11 Uniformity of Claims, and the National Reference System for the Clinical Laboratory. We also include a list of applicable national and international organizations. Calcium assay by atomic absorption spectrometry using an imprecise diluter illustrates the application of the evaluation protocols as a method validation tool.

Chemistry, Clinical

Linearity and calibration. A clinical laboratory perspective.

This article discusses the relationship of calibration and linearity using the example of glutaraldehyde assayed by high-performance liquid chromatography. Assuming adequate precision and a lack of interference, the relationship of calibration to a method's linear range becomes all important to achieving quality analytical results. Linearity is an objective description of the relationship between a quantitative method's final answer and true analyte concentration. Calibration brings this relationship into correspondence with calibrator concentration. The reportable range is that range within which a specified method produces results within defined allowable error without resorting to dilution of the specimen. The reportable range assumes a linear relationship between true analyte concentration and analytical results.

Calibration

Effects of caffeine on pressor regulation during rest and exercise in men at risk for hypertension.

Caffeine-induced blood pressure elevations are well documented in habitual consumers, occurring through both vasoconstrictive and cardiostimulatory actions. Whether caffeine hinders pressor regulation during exercise has been uncertain, particularly in those at risk for hypertension. Thus effects of caffeine versus placebo were studied during supine bicycle exercise in healthy men (ages 20 to 35). Hypertension risk was defined during screening: high risk (HRISK) = 135 to 154/85 to 94 mm Hg plus parental hypertension (n = 20); low risk (LRISK) = less than or equal to 132/84 mm Hg and no parental hypertension (n = 14). Exaggerated pressor responses (greater than or equal to 230/100 mm Hg) seen during exercise after placebo identified a subgroup of seven HRISKs indistinguishable at rest from the remaining HRISK men. This subgroup showed a larger resting diastolic response to caffeine (p less than 0.05) than LRISKs and other HRISKs. Compared with placebo, caffeine increased the number of LRISK (0% to 36%) and HRISK (35% to 50%) men reaching abnormal exercise blood pressures, and blunted normal increments in cardiac index at higher workloads among HRISK men (p = 0.05). Thus restriction of caffeine before exercise might benefit persons with either risk for hypertension or unusual sensitivity to caffeine.

Adult

Hypertension risk and caffeine's effect on cardiovascular activity during mental stress in young men.

Examined the cardiovascular effects of caffeine plus behavioral stress in men low versus high in risk of essential hypertension. Caffeine (3.3 mg/kg, equivalent to 2 to 3 cups of coffee) or placebo was given on alternate days to 19 low-risk men (negative for parental hypertension and low-normal resting blood pressure, BP) and 20 high-risk men (positive history, high-normal BP). Forty minutes later, each worked for 15 min on a demanding psychomotor task during which BP, cardiac output, and vascular resistance were determined. During rest, caffeine raised vascular resistance in both groups. During the task, it supra-additively increased the systolic BP response by enhancing the rise in cardiac output, producing equivalent BP rises in both groups. Due to the higher resting pressures of the high-risk men, caffeine plus the task resulted in 50% of these having transient BP of 140/90 mg Hg or greater. Caffeine in combination with mental stress may produce undesirable BP in those at risk for hypertension.

Adult

Survival of primates in LD100 septic shock following therapy with antibody to tumor necrosis factor (TNF alpha).

The purpose of this study was to determine the efficacy of treatment with anti-TNF monoclonal antibody in preventing the deleterious effects of sepsis in a nonhuman primate. Experiments were carried out on anesthetized baboons intravenously infused with a lethal dose of Escherichia coli (E. coli). Twelve baboons (six control and six experimental) received 2 hr infusions of E. coli. The experimental group was administered a bolus of anti-TNF antibody, 15 mg/kg, 30 min after beginning the E. coli infusion. Control baboons lived an average of 19 hr (12-34 hr). All antibody-treated baboons survived more than 7 days with a significantly improved quality of life compared to the control group. Although some adverse changes occurred during the monitoring period in surviving baboons, they maintained nearly normal arterial pressures, and serum urea nitrogen and creatinine concentrations. The severe histopathologic changes in lungs, liver, adrenals, kidneys, and spleen documented at death in baboons receiving E. coli only were absent after 7 days in baboons given E. coli and early post-treatment with antibody to TNF.

Animals

Caffeine may potentiate adrenocortical stress responses in hypertension-prone men.

The effect of caffeine on blood cortisol levels and blood pressures was examined during rest and in response to a challenging psychomotor task in men with a low versus high risk of essential hypertension. Thirty-four healthy men ages 21-35 years were selected such that 17 were at high risk for hypertension (positive parental history and screening blood pressures of 135/85-155/95 mm Hg) and 17 were at low risk (negative parental history and no pressures above 132/84 mm Hg). Testing consisted of quiet rest (20 minutes); oral placebo (grapefruit juice) or caffeine administration (3.3 mg/kg in grapefruit juice); rest during a postdrug absorption period (40 minutes); work on an unsignalled simple reaction time task (15 minutes); and quiet rest (20 minutes). Blood pressures were recorded at 2-minute intervals, and blood samples were withdrawn via an indwelling catheter at the end of the baseline, drug absorption, task, and recovery periods. The combination of task plus caffeine produced the highest blood pressures in men at risk for hypertension. Cortisol levels were found to be sustained during rest in members of the high risk group after they had consumed caffeine, whereas members of the low risk group showed a modest decline. The high risk subjects also showed a significant rise in cortisol during (+3.7 micrograms/dl) and after (+4.0 micrograms/dl) work on the reaction time task after caffeine consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone

Effect of behavior state on caffeine's ability to alter blood pressure.

Caffeine use during exposure to mental stress is an extremely common occurrence. Because both have been shown to alter blood pressure (BP) and its underlying hemodynamic mechanisms, the potential exists for additive or even synergistic effects. Changes in heart rate, BP and noninvasive thoracic impedance measures of left ventricular function were examined in young men (ages 20 to 36) at rest and during a demanding behavioral task performed 40 minutes after predosing with caffeine (3.3 mg/kg, equivalent to 2 to 3 cups of coffee) or placebo in a double-blind crossover design. All subjects were healthy young men without history of cardiovascular disease, regular use of nicotine, recreational or prescription drugs or caffeine intolerance. Caffeine abstinence was required for 12 hours before each test session. Systolic and diastolic BP were elevated by both caffeine and the behavioral task alone (p less than 0.01 for each); when combined, caffeine's pressor effects were additive to those of the behavioral task. However, caffeine's pressor effect was produced by different mechanisms depending on the behavioral state. Caffeine increased systemic vascular resistance (p less than 0.01) under resting conditions, but it enhanced cardiac output (p less than 0.01) during behavioral arousal associated with the task. The combined influence of caffeine and the task increased the number of men in whom peak systolic BP reached hypertensive levels, and also synergistically increased cardiac minute work (p less than 0.01) and the rate-pressure product estimate of myocardial oxygen demand (p less than 0.05). Implications of these findings are discussed for long standing theoretical disputes regarding caffeine, its health consequences, and for methodologic issues in behavioral and clinical studies.

Adult

Evaluation of naloxone therapy for Escherichia coli sepsis in the baboon.

This study evaluated the effects of naloxone hydrochloride in the treatment of Escherichia coli-induced shock in baboons. The baboons were studied for 12 hours and monitored for survival times. All baboons were intravenously infused for two hours with E coli and treated as follows: group 1, E coli (control); group 2, E coli plus naloxone hydrochloride, 0.5 mg/kg bolus plus 0.5 mg/kg/h for 9.5 hours; and group 3, E coli plus naloxone hydrochloride, 2.0 mg/kg bolus plus 2.0 mg/kg/h for 3.8 hours. Naloxone was administered after arterial pressure had reached the nadir (more than two hours following initiation of E coli infusion). Mean arterial pressure was supported by the lower dose of naloxone; however, sustained leukopenia and neutropenia were not reversed by its infusion. Naloxone prevented the increase in plasma beta-endorphin level and blunted the increase in plasma cortisol level. Despite these effects, naloxone did not prevent multiple-organ disease and did not decrease mortality.

Animals

Caffeine enhances the physiological response to occupational stress in medical students.

Caffeine (3.3 mg/kg) was tested against a placebo in 20 male medical students during periods of low (no exams) versus high (final exams) work stress. On each of 8 test days, heart rate and blood pressure were measured at baseline and over a 40-min postdrug interval; immediately afterward, blood was drawn to test plasma cortisol and serum lipid concentrations. Exams increased heart rate (p less than .005) and systolic blood pressure (p less than .02). Caffeine decreased heart rate (p less than .0001) and increased systolic blood pressure (p less than .005), diastolic blood pressure (p less than .0001), plasma cortisol levels (p less than .01), and serum cholesterol levels (p less than .02). Caffeine effects were additive with those of exams, and together they increased the number of men showing systolic blood pressures in the borderline hypertensive range. Thus, caffeine use during periods of increased occupational stress may enhance the cumulative stress response.

Adult

Tobramycin therapy for lethal sepsis in the dog.

Antimicrobial effectiveness and effect on survival of single-dose vs. multiple-dose aminoglycoside antibiotic therapy (with and without steroid) for lethal sepsis were evaluated. Adult dogs of either sex were anesthetized, divided into five groups, and infused iv for one hour with Escherichia coli. Group A was given no drug. Group B was given a 45-mg/kg, 10-min iv injection of tobramycin (TOB) at 65 min. Group C was given a 3-mg/kg, 10-min TOB injection at 65 min, followed by an 8.25-mg/kg iv infusion for 285 min, and three 11.25-mg/kg intramuscular injections at 6, 12, and 18 h (total 45 mg/kg). Group D was given the same TOB regimen as B, plus a 30-mg/kg iv injection and 30-mg/kg iv infusion of methylprednisolone sodium succinate (MPSS) from 15 to 360 min. Group E was given the same TOB regimen as C, plus the same MPSS regimen as D. Treated dogs also received 11.25 mg/kg of TOB daily for 4 days. The percent surviving more than 7 days was 0, 0, 17%, 83%, and 83%, for groups A through E, respectively. By 4 h, TOB-treated groups had significantly (p less than .05) lower E. coli blood levels than group A. Also E. coli levels in group B were significantly (p less than .05) lower than those in groups C, D, or E. High trough serum TOB concentrations were associated with death and very low levels with recovery. Serum urea nitrogen and creatinine concentrations increased in all groups, but returned to normal by 7 days in survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of prior administration of steroids upon recovery from lethal sepsis.

The effects upon survival of large doses of steroid administered to dogs prior to challenging them with lethal sepsis was evaluated in this study. Dogs were given 30 milligrams per kilogram of body weight per day of methylprednisolone sodium succinate for one, two or eight days and then were infused with 9.72 +/- 0.35 X 10(9) Escherichia coli per kilogram of body weight. All dogs in group 1 (n equals six) not given steroid died within 25 hours. Of the dogs in group 2 (n equals 12) given one or two doses of steroid previously, 42 per cent permanently survived (more than seven days). All dogs in group 3 (n equals five) given eight daily doses of steroid prior to infusion of Escherichia coli died within 17 hours. Dogs in group 4 (n equals six) were given eight daily doses of steroid prior to infusion of Escherichia coli and treated on the day of infusion of Escherichia coli with a regimen of methylprednisolone and gentamicin sulfate which results in a 100 per cent survival rate when given to dogs that have not received prior treatment with steroid. Thirty-three per cent of the dogs in group 4 permanently survived. One or two daily large doses of steroid did not detrimentally affect survival of the dogs. Eight days of steroid administration suppressed endogenous cortisol production. When the dogs were treated with six hours of steroid-antibiotic therapy, survival benefits were limited.

Adrenal Cortex Hormones

Effects of caffeine on vascular resistance, cardiac output and myocardial contractility in young men.

The mechanisms by which caffeine typically elevates blood pressure (BP) in humans have not been previously examined using a placebo-controlled design. Accordingly, oral caffeine (3.3 mg/kg body weight, equivalent to 2 to 3 cups of coffee) was given on 2 days and a placebo was given on 1 day to 15 healthy young men using a double-blind, crossover procedure. All 3 test sessions were held during a week of caffeine abstinence. Multiple measurements were made on subjects at rest (baseline values) and over a 45-minute interval after ingestion of caffeine for BP, heart rate, systolic time intervals and thoracic impedance measures of ventricular function. Baseline measurements were highly reliable for each subject across all sessions and yielded means for placebo vs caffeine days that were not different. Caffeine increased systolic and diastolic BP (p less than 0.01) and decreased heart rate (p less than 0.05). The pressor effect was due to progressively increased systemic vascular resistance and resulted in greater stroke work (p less than 0.01). There was no indication that caffeine increased cardiac output or contractility. These actions of caffeine were replicable when each caffeine day was tested separately against the placebo day. These results suggest that caffeine use by persons with cardiovascular diseases should be examined to determine whether caffeine's enhancement of vascular resistance may contribute to systematic hypertension and/or create excessive demands for cardiac work.

Adult

Quantitation of zinc in nitric acid-digested plasma by atomic absorption spectrophotometry.

Human plasma, digested in a screw-capped Teflon vial for 1 h at 130 degrees C in concentrated nitric acid, is assayed for zinc by atomic absorption spectrophotometry using a single-slot, 10-cm burner and air/acetylene flame. The assay is linear to 10.00 mg Zn/liter, recovery averages 100.9%, and inter- and intraassay coefficients of variation are 5.9 and 1.9%. With this method, there is no burner clogging or adjustment necessary for sample viscosity. Sodium chloride does not interfere with the assay. The linear regression data of the standard curve for milligrams of Zn per liter (x) and milliabsorbance units (y) is y = 40x + 0.001.

Humans

Corticosteroid/antibiotic treatment of adrenalectomized dogs challenged with lethal E. coli.

Adrenalectomized animals are extremely sensitive to endotoxin and die quickly when given small doses. A six hour administration of the corticosteroid, methylprednisolone sodium succinate (MPSS), combined with the antibiotic, gentamicin sulfate (GS), promotes complete recovery of dogs with intact adrenals administered LD100 E. coli. The aim of the present study was to determine if this early administered treatment would protect adrenalectomized dogs from overwhelming lethal doses of E. coli. Dogs were infused with MPSS from fifteen minutes to six hours after the onset of E. coli administration and with GS after administration of all E. coli. Animals given only E. coli died in 2.6 (+/- 0.3) hours, while those given no E. coli, or E. coli plus steroid/antibiotic, survived longer than 100 hours. Arterial pressure, pH, pO2, hematocrit, lactate, and glucose concentrations were maintained near control values in animals receiving steroid/antibiotic infusions. Adrenalectomized dogs infused with corticosteroid/antibiotic recovered completely from shock even though the treatment period was limited to the first 6 hours after lethal E. coli infusion. Findings indicate that animals treated with MPSS/GS after E. coli ultimately succumbed to adrenal insufficiency rather than from the E. coli insult and thus recovery from shock itself was complete.

Adrenal Cortex Hormones

Evaluation of naloxone for therapy of Escherichia coli shock. Species differences.

Dogs and baboons were infused intravenously (IV) with Escherichia coli and treated with the opiate antagonist, naloxone hydrochloride, and the antibiotic, gentamicin sulfate, to determine the therapeutic efficacy of naloxone. Naloxone hydrochloride (2 mg/kg) was injected IV when one fourth of the E coli had been infused and then infused at 2 mg/kg/hr (six hours for dogs and 12 hours for baboons). Four of five naloxone-treated dogs survived permanently (greater than seven days), while all dogs that were given only E coli died. Arterial BP, blood glucose levels, PCO2, and PO2 were supported at higher levels and lesions of the gastrointestinal tract were prevented in naloxone-treated dogs. A steady decline in blood glucose levels after an initial hyperglycemia was observed in naloxone-treated baboons, indications of peripheral vasoconstriction were noted, and all baboons died within 42 hours.

Animals

Effectiveness of modified steroid-antibiotic therapies for lethal sepsis in the dog.

Dogs permanently recover (survive at least seven days) from lethal doses of Escherichia coli when treated early with intravenous (IV) intermittent infusions of methylprednisolone sodium succinate and gentamicin sulfate. We evaluated the therapeutic effectiveness of constant or bolus IV infusion of methylprednisolone combined with gentamicin or netilmicin sulfate. Four groups of anesthetized dogs were infused for one hour with E coli and treated as follows (% survival indicated): no treatment (0%); constant infusion of methylprednisolone and gentamicin (100%); bolus infusion of methylprednisolone and gentamicin (57%); and constant infusion of methylprednisolone and netilmicin (83%). Constant or bolus infusion of methylprednisolone was begun 15 minutes after E coli infusion was started. Gentamicin or netilmicin administration was begun when all organisms had been infused. The probability of recovery from shock was significantly increased when dogs were treated with constant infusion of methylprednisolone and intermittent infusions of gentamicin or netilmicin, but was only moderately increased when treated with intermittent bolus infusions of methylprednisolone and intermittent infusions of gentamicin.

Animals

Prevention or amelioration of morphologic lesions in LD100 E coli-shocked baboons with steroid/antibiotic therapy.

We have documented the effectiveness of methylprednisolone sodium succinate (MPSS) and gentamicin sulfate (GS) therapy for LD100 E coli-induced shock in the baboon. We sequentially delayed initiation of MPSS infusion from 30 to 120 min and then to 240 min after onset of a 2-h E coli infusion. Treatment resulted in 100%, 85%, and 65% survival respectively. In this study we evaluated tissue taken at autopsy in the three MPSS/GS treatment studies including untreated baboons and those treated with GS only. When animals died (3-49 h) or were sacrificed (7-71 days), tissues were removed, coded, and prepared for histopathologic evaluation by light microscopy. On the basis of morphologic changes animals split into two groups: baboons with little or no tissue alterations (survivors), and those with multiple organ damage (nonsurvivors). Combinations of mild to massive congestion, edema, hemorrhage, fibrin thrombi, increased numbers of polymorphonuclear leukocytes (PMNs), and necrosis of the adrenal glands, liver, kidneys, lungs, and spleen of nonsurvivors were prevented or ameliorated in the MPSS/GS-treated surviving baboons. Data demonstrate the MPSS/GS therapy prevents or reverses the multiple organ damage and increases survival in lethal septic shock.

Adrenal Glands