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Biomedical subjects

R O Brown

Publications and source records attributed to R O Brown.

At least 19 recordsLinked to original sources

Visual motion of missing-fundamental patterns: motion energy versus feature correspondence.

Missing-fundamental gratings, generated by subtracting the fundamental Fourier components from square-wave gratings, appear to move backward when presented in quarter-cycle jumps, even though their edges and features all move forward. We used variants of these stimuli to test current models of motion perception. We found that missing-fundamental plaids, constructed from orthogonal missing-fundamental gratings, also appear to move backward. Forward motion was restored to missing-fundamental gratings and plaids by adding back small fractions of the original fundamental. In-phase and antiphase addition of the fundamental had similar effects on the perceived motion, despite having markedly different effects on the features, appearances and zero-crossings of the stimuli. The critical amplitude of fundamental needed to restore forward motion to plaids was the same as that needed to restore forward motion to their isolated component gratings, indicating that the plaids' emergent features, such as edge intersections and 'blobs', made little or no contribution to the perceived direction of motion in these stimuli. In two derivative experiments, missing-fundamental chromatic gratings and plaids, at approximate isoluminance, and missing-fundamental luminance barberpoles, also generated backward perceived motions, and these were also reversed by in-phase or antiphase addition of small amounts of fundamental.

Fourier Analysis↗

Sequential group trial to determine gastrointestinal site of absorption and systemic exposure of azathioprine.

Azathioprine (AZA) is used in the treatment of patients with refractory inflammatory bowel disease; however, its use is limited because of systemic toxicity associated with long-term use. Ileocecal delivery of AZA might be advantageous if local intestinal therapeutic effects could be provided with decreased systemic side effects. Decreased cecal systemic absorption would allow higher dosages of AZA to be administered. A two-phase study was performed to compare the systemic exposure of AZA and 6-mercaptopurine (6-MP) following administration of AZA into the stomach, jejunum, and cecum and to compare the systemic exposure to AZA and 6-MP following administration of three different dosages of AZA into the cecum. In phase I, six healthy male volunteers received three 50 mg sequential doses of AZA via an oral tube directly placed into the stomach, jejunum, and cecum, respectively. In phase II, six healthy male volunteers received three different dosages (50, 300, 600 mg of AZA) into the cecum. Plasma concentrations of AZA and 6-MP at various times were quantified and area under the plasma concentration-time curve (AUC) and mean residence time (MRT) were determined. No significant differences in the AUC of AZA were seen at the different sites. The AUC of 6-MP following administration of AZA into the jejunum (67.0 +/- 30.1 ng x hr/ml) was higher compared to the stomach (39.9 +/- 38.1 ng/hr/ml) and cecum (29.2 +/- 10.9 ng x hr/ml). Jejunal absorption was 68% higher than absorption from the stomach and 129% higher than that of the cecum. Gastric absorption was 27% higher than that of the cecum. Increased dosages given into the cecum resulted in increased AUCs of AZA and 6-MP. The AUCs of AZA following 50, 300, and 600 mg dosages were 16.9 +/- 7.4, 52.3 +/- 67.2, and 132 +/- 151 ng x hr/ml, respectively, and the AUCs of 6-MP were 22.2 +/- 14.9, 63.4 +/- 50.6, and 104 +/- 115 ng x hr/ml, respectively. Systemic exposure to 6-MP is reduced following administration of AZA into the cecum, most likely secondary to reduced absorption of 6-MP from the colon. Higher dosages of AZA presented to the cecum do result in increased systemic absorption, but may still allow more drug to be administered with less toxicity than the same dose received orally.

Adolescent↗

Sequential single doses of cisapride, erythromycin, and metoclopramide in critically ill patients intolerant to enteral nutrition: a randomized, placebo-controlled, crossover study.

OBJECTIVE: To evaluate the comparative efficacy of enteral cisapride, metoclopramide, erythromycin, and placebo for promoting gastric emptying in critically ill patients with intolerance to gastric enteral nutrition (EN). DESIGN: A randomized, crossover study. SETTING: Adult medical intensive care unit at a university-affiliated private hospital and trauma intensive care unit at a university teaching hospital. PATIENTS: Ten adult, critically ill, mechanically ventilated patients not tolerating a fiber-containing EN product defined as a single aspirated gastric residual volume >150 mL or two aspirated gastric residual volumes >120 mL during a 12-hr period. INTERVENTIONS: Patients received 10 mg of cisapride, 200 mg of erythromycin ethylsuccinate, 10 mg of metoclopramide, and placebo as 20 mL of sterile water every 12 hrs over 48 hrs. Acetaminophen solution (1000 mg) was administered concurrently. Gastric residual volumes were assessed, and plasma acetaminophen concentrations were serially determined by TDx between 0 and 12 hrs to evaluate gastric emptying. MEASUREMENTS AND MAIN RESULTS: Gastric residual volumes during the study were not significantly different between agents. No differences in area under the concentration vs. time curve or elimination rate constant were identified between agents. Metoclopramide and cisapride had a significantly shorter mean residence time of absorption than erythromycin (6.3+/-4.5 [SEM] mins and 10.9+/-5.8 vs. 30.1+/-4.5 mins, respectively [p<.05]). Metoclopramide (9.7+/-15.3 mins) had a significantly shorter time to peak concentration compared with erythromycin and placebo (60.7+/-8.1 and 50.9+/-13.5 mins, respectively [p<.05]). The time to onset of absorption was significantly shorter for metoclopramide vs. cisapride (5.7+/-4.5 vs. 22.9+/-5.7 mins [p<.05]). CONCLUSION: In critically ill patients intolerant to EN, single enteral doses of metoclopramide or cisapride are effective for promoting gastric emptying in critically ill patients with gastric motility dysfunction. Additionally, metoclopramide may provide a quicker onset than cisapride.

Acetaminophen↗

Oxandrolone in trauma patients.

STUDY OBJECTIVE: To determine the effect of oxandrolone administration on nutritional and clinical outcomes after multiple trauma. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Level 1 trauma center in a university teaching hospital. PATIENTS: Sixty-two patients requiring enteral nutrition, 60 of whom completed the study. INTERVENTION: Patients were randomized to receive either oxandrolone 10 mg or placebo twice/day for a maximum of 28 days. MEASUREMENTS AND MAIN RESULTS: Total urinary nitrogen, prealbumin, nitrogen balance, total body water, and body cell mass were measured on day 1 of enteral nutrition and then at day 7, day 10, and study exit. Patients were assessed daily for metabolic and infectious complications. The two groups were similar for demographics and dosage of enteral nutrition. Measurement of total urinary nitrogen at study entry showed both groups to be highly catabolic (oxandrolone 17.2 +/- 4.9, placebo 19.1 +/- 10.8 g/day, NS). On days 7 and 10, total urinary nitrogen increased in both groups; however, there was no significant difference between groups. Nitrogen balance was negative throughout the study in each group. Body cell mass decreased slightly in both groups over the study period. Prealbumin serum concentrations increased significantly in both groups at day 10 and study exit compared with study entry. The groups did not differ significantly for length of hospital stay (oxandrolone 30.8 +/- 17.9, placebo 27.0 +/- 25.7 days), length of intensive care unit stay (oxandrolone 17.1 +/- 7.8, placebo 15.5 +/- 9.7 days), and frequency of pneumonia or sepsis (oxandrolone 48, placebo 43 episodes). CONCLUSION: Oxandrolone 20 mg/day does not have obvious benefit in nutritional and clinical outcomes during the first month after multiple trauma.

Adult↗

Measured energy expenditure of tube-fed patients with severe neurodevelopmental disabilities.

OBJECTIVE: To determine measured resting energy expenditure (REE) of nonambulatory tube-fed patients with severe neurological neurodevelopmental disabilities. METHODS: Twenty patients were prospectively studied. Only steady state indirect calorimetry measurements were taken. All measurements were conducted using a canopy system. Nutritional needs were met entirely by enteral feedings via a permanent ostomy. RESULTS: REE was widely distributed from 16 kcals/kg/day to 39 kcals/kg/day. The mean REE (888+/-176 kcals/day) of the patients was significantly (p<0.01) lower than predicted as estimated by the Harris-Benedict equations (1081+/-155 kcals/day) and World Health Organization equations (1194+/-167 kcals/day). Fat-free mass (FFM) was the best parameter for predicting REE. Two predictive equations were developed that are not significantly biased and more precise (< or =15% error) than conventional predictive formulas. CONCLUSION: Conventional formulas for estimating energy expenditure are inaccurate and generally overestimate measured energy expenditure of nonambulatory patients with severe developmental disabilities.

Adolescent↗

Management of the neck in nonmelanocytic cutaneous carcinomas.

Cutaneous malignancies are the most common causes of cancer in the United States, and the preponderance occur in the head and neck region. From 0.3% to 13.7% of cutaneous squamous cell carcinomas and from 0.0028% to 0.4% of cutaneous basal cell carcinomas metastasize to the cervical nodes. A description of the head and neck cutaneous lymphatic drainage is presented, followed by recommendations regarding neck dissection modifications appropriate to the primary sites and nodal eschalons involved.

Basal Cell Carcinoma↗

Color appearance depends on the variance of surround colors.

BACKGROUND: The perceived color at each point in a visual scene depends on the relationship between light signals from that point, and light signals from surrounding areas of the scene. In the well known phenomenon of simultaneous color contrast, changing the overall brightness or hue of an object's surround induces a complementary shift in the perceived brightness or hue of the object's color. Color contrast is thought to contribute to color constancy with changes in illumination. RESULTS: We report a new type of simultaneous color contrast, in which changing only the variance (i.e. contrasts and saturations), but not the mean, of colors in a test spot's surround induces a complementary shift in the perceived contrast and saturation of the test spot's color. Objects appear much more vivid and richly colored against low-contrast, gray surrounds than against high-contrast, multicolored surrounds. CONCLUSIONS: Color appearance depends not just on the mean color of the surround, but also on the distribution of surround colors about the mean. This novel form of simultaneous color contrast is inconsistent with a variety of models of color appearance, including those based on sensitivity regulation at the receptor level, and those in which the effects of complex surrounds on color appearance can be reduced to adaptation to the illuminant or induction from a homogeneous 'equivalent surround'. It tends to normalize the gamut of perceived colors in each visual scene and may also contribute to color constancy under viewing conditions that affect contrast.

Color Perception↗

Intravenous insulin-like growth factor-I (IGF-I) in moderate-to-severe head injury: a Phase II safety and efficacy trial.

The purpose of this study was to determine the effect of insulin-like growth factor-I (IGF-I) on the catabolic state and clinical outcome of head-injured patients. Thirty-three patients between the ages of 18 and 59 years with isolated traumatic head injury and Glasgow Coma Scale (GCS) scores of 4 to 10 were randomized to one of two groups. All patients received standard neurosurgical intensive care plus aggressive nutritional support; the patients in the treatment group also received intravenous therapy with continuous IGF-I (0.01 mg/kg/hour). During the 14-day dosing period, the control patients lost weight, whereas treated patients gained weight despite a significantly higher measured energy expenditure and lower caloric intake (p = 0.02). Daily glucose concentrations and nitrogen outputs were greater in control patients (p = 0.03) throughout the study period. During Week 1, only treated patients achieved positive nitrogen balance. Fifteen of 17 treated and 13 of 16 control patients survived the 1st week. No deaths occurred in patients whose serum IGF-I concentrations were higher than 350 ng/ml. Dichotomized Glasgow Outcome Scale scores for patients with baseline GCS scores of 5 to 7 improved from poor to good for eight of 12 treated patients but for only three of 11 control patients (p = 0.06). Eight of 11 treated patients with serum IGF-I concentrations that were at least 350 ng/ml achieved moderate-to-good outcome scores at 6 months, compared to only one of five patients with lower concentrations (p < 0.05). These findings indicate that pharmacological concentrations of IGF-I may improve clinical outcome and nitrogen utilization in patients with moderate-to-severe head injury.

Clinical Trial↗

The effect of alpha-adrenergic antagonism upon nitrogen loss during endotoxemia.

Sixty male Sprague-Dawley rats were randomized to receive parenteral nutrition (PN) only; PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide (PN + LPS) at 6 mg.kg-1.d-1; or PN plus LPS plus a continuous infusion of the alpha-adrenergic antagonist phentolamine (PN + LPS + PHEN) at 5 mg.kg-1.d-1 or 20 mg.kg-1.d-1 for 48 h. All animals received isocaloric, isonitrogenous PN. LPS significantly lowered nitrogen balance (mmol/48 h) from PN control; however, addition of PHEN substantially worsened nitrogen balance compared with LPS (14.2 +/- 3, 2.4 +/- 5.2, -1.6 +/- 4.5, -0.8 +/- 5.4, for the PN, PN + LPS, PN + LPS + PHEN5 and PN + LPS + PHEN20 groups, respectively; P < 0.0001). Urinary 3-methylhistidine/creatinine ratio (3-meH/creat) paralleled the nitrogen balance data (0.30 +/- 0.09, 0.45 +/- 0.12, 0.51 +/- 0.14, 0.60 +/- 0.12, respectively; P < 0.0001). The high-dose PHEN resulted in 82 +/- 9% blockade. To ascertain if any beneficial effect upon body protein loss is achieved during severe stress, 30 rats were given PN + LPS at 12 mg.kg-1.d-1 or PN + LPS12 + PHEN20. These data showed similar changes in nitrogen balance and 3-methylhistidine/creatinine with the use of PHEN during severe endotoxemia. alpha-adrenergic antagonism with PHEN worsens body protein loss as measured by nitrogen balance and 3-methylhistidine/creatinine in PN-fed endotoxemic rats.

Adrenergic alpha-Antagonists↗

Dose-dependent effect of octreotide on nitrogen retention and glucose homeostasis in response to endotoxemia in parenterally fed rats.

OBJECTIVE: This study compared the effect of different doses of octreotide on glucose and protein homeostasis in rats receiving concomitant lipopolysaccharide and parenteral nutrition infusions. METHODS: Sixty-six male Sprague Dawley rats (185 to 220 g) were randomized to receive parenteral nutrition only (PN), PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 mg/kg/day (LPS), PN plus LPS plus octreotide at 10 micrograms/kg/day (LPS + Oct 10), 100 micrograms/kg/day (LPS + Oct 100), or 1000 micrograms/kg/day (LPS + Oct 1000) for 48 hours. Prior to randomization all animals received isocaloric and isonitrogenous PN (170 kcal/kg/day as glucose and 1.1 g N/kg/day) and were kept nil per os except for water ad libitum. Nitrogen balance, urinary 3-methylhistidine/creatinine ratio, serum glucose concentration, and incidence of glycosuria were compared between groups. Serum urea nitrogen (SUN) changes were incorporated into the cumulative 48 hour nitrogen balance. ANOVA, Duncan's multiple range test, and Fisher's Exact Test were used for statistical analysis. RESULTS: Nitrogen balance (mg/48 hours) was significantly lower in all four groups receiving LPS +/- Oct when compared to the control group receiving PN alone. SUN (mg/dL) was significantly higher in all four groups receiving LPS +/- Oct when compared to control. There were no statistically significant differences in nitrogen balance or SUN among the four groups receiving LPS +/- Oct. The ratio of urinary 3-methylhistidine/ creatinine was significantly higher in the LPS + Oct 1000 group compared to the PN group (0.77 +/- 0.37 vs. 0.42 +/- 0.24, p < 0.05). Serum glucose concentrations and incidence of glycosuria among the five groups were not significantly different. CONCLUSIONS: Endotoxin significantly reduces nitrogen balance compared to controls fed PN. Octreotide does not significantly improve nitrogen retention or glucose homeostasis in endotoxemic parenterally fed rats.

Animals↗

Intravenous insulin-like growth factor-I (IGF-I) in moderate-to-severe head injury: a phase II safety and efficacy trial.

The purpose of this study was to determine the effect of insulin-like growth factor-I (IGF-I) on the catabolic state and clinical outcome of head-injured patients. Thirty-three patients between the ages of 18 and 59 years with isolated traumatic head injury and Glasgow Coma Scale (GCS) scores of 4 to 10 were randomized to one of two groups. All patients received standard neurosurgical intensive care plus aggressive nutritional support; the patients in the treatment group also received intravenous therapy with continuous IGF-I (0.01 mg/kg/hour). During the 14-day dosing period, the control patients lost weight, whereas treated patients gained weight despite a significantly higher measured energy expenditure and lower caloric intake (p = 0.02). Daily glucose concentrations and nitrogen outputs were greater in control patients (p = 0.03) throughout the study period. During Week 1, only treated patients achieved positive nitrogen balance. Fifteen of 17 treated and 13 of 16 control patients survived the 1st week. No deaths occurred in patients whose serum IGF-I concentrations were higher than 350 ng/ml. Dichotomized Glasgow Outcome Scale scores for patients with baseline GCS scores of 5 to 7 improved from poor to good for eight of 12 treated patients but for only three of 11 control patients (p = 0.06). Eight of 11 treated patients with serum IGF-I concentrations that were at least 350 ng/ml achieved moderate-to-good outcome scores at 6 months, compared to only one of five patients with lower concentrations (p < 0.05). These findings indicate that pharmacological concentrations of IGF-I may improve clinical outcome and nitrogen utilization in patients with moderate-to-severe head injury.

Adolescent↗

Mononuclear blood cell magnesium content and serum magnesium concentration in critically ill hypomagnesemic patients after replacement therapy.

Magnesium (Mg) deficiency, commonly diagnosed as hypomagnesemia based upon low serum Mg concentrations, is a frequent electrolyte abnormality in critically ill patients. Intravenous replacement therapy is empiric and serum Mg concentrations have traditionally been used as guidelines for measuring efficacy. Recent studies have shown that the Mg content of mononuclear blood cells (MBCs) may provide a better index for Mg status than serum concentrations. The purpose of this study was to evaluate the effects of intravenous Mg replacement therapy on MBC Mg content and serum Mg concentrations in critically ill hypomagnesemic patients. Adult patients admitted to the trauma intensive-care unit (ICU) with serum Mg concentration < or = 0.6 mmol/L (< or = 1.5 mg/dL) were considered for study entry. Patients with severe renal disease (Scr > 133 mumol/L), pregnancy, or those who were seropositive for HIV were excluded. Ten patients with moderate (> 0.4-0.6 mmol/L [> 1.0-1.5 mg/dL]) and severe (< or = 0.4 mmol/L [< or = 1.0 mg/dL]) hypomagnesemia received 0.5 and 0.75 mmol/kg of intravenous MgSO4, respectively, over 24 h. MBC Mg content and serum concentrations of magnesium, phosphorus, calcium, sodium, potassium, blood urea nitrogen, creatinine, glucose, and albumin were measured at baseline (0 h), end of infusion (24 h), 36 h, and 48 h. Data were analyzed using ANOVA with repeated measures and a P value < 0.05 was considered significant. Serum Mg concentrations increased significantly from baseline to 48 h (0.5 +/- 0.1 to 0.8 +/- 0.2 mmol/L, P < 0.001). MBC Mg content did not change significantly within the study period (2.6 +/- 1.0 to 3.0 +/- 1.3 fmol/cell, P > 0.7). The doses of MgSO4 (0.5-0.75 mmol/kg) used in this study increased serum Mg concentrations, but did not result in a statistically significant change of MBC Mg content in this group of trauma ICU patients.

Accidents, Traffic↗

A randomized trial of isonitrogenous enteral diets after severe trauma. An immune-enhancing diet reduces septic complications.

OBJECTIVE: The authors randomized patients to an enteral diet containing glutamine, arginine, omega-3 fatty acids, and nucleotides or to an isonitrogenous, isocaloric diet to investigate the effect of septic outcome. A third group of patients, without enteral access but eligible by severity of injury, served as unfed controls and were studied prospectively to determine the risk of infection. SUMMARY BACKGROUND DATA: Laboratory and clinical studies suggest that diets containing specialty nutrients, such as arginine, glutamine, nucleotides, and omega-3 fatty acids, reduce septic complications. Unfortunately, most clinical trials have not compared these diets versus isonitrogenous, isocaloric controls. This prospective, blinded study randomized 35 severely injured patients with an Abdominal Trauma Index > or = 25 or a Injury Severity Score > or = 21 who had early enteral access to an immune-enhancing diet ([IED] Immun-Aid, McGaw, Inc., Irvine, CA; n = 17) or an isonitrogenous, isocaloric diet (Promote [Ross Laboratories, Columbus, OH] and Casec [Mead-Johnson Nutritionals, Evansville, IN]; n = 18) diet. Patients without early enteral access but eligible by severity of injury served as contemporaneous controls (n = 19). Patients were evaluated for septic complications, antibiotic usage, hospital and intensive care unit (ICU) stay, and hospital costs. RESULTS: Two patients died in the treatment group and were dropped from the study. Significantly fewer major infectious complications (6%) developed in patients randomized to the IED than patients in the isonitrogenous group (41%, p = 0.02) or the control group (58%, p = 0.002). Hospital stay, therapeutic antibiotics, and the development of intra-abdominal abscess was significantly lower in patients receiving the IED than the other two groups. This improved clinical outcome was reflected in reduced hospital costs. CONCLUSIONS: An IED significantly reduces major infectious complications in severely injured patients compared with those receiving isonitrogenous diet or no early enteral nutrition. An IED is the preferred diet for early enteral feeding after severe blunt and penetrating trauma in patients at risk of subsequent septic complications. Unfed patients have the highest complication rate.

Adult↗