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Biomedical subjects

C Weissman

Publications and source records attributed to C Weissman.

At least 73 records · Page 4Linked to original sources

Prolonged corticosteroid treatment exerts transient inhibitory effect on prostaglandin E2 release from rabbits' eyes.

In humans, the retina and choroid (the photoreceptor and its vascular layers, respectively), are affected by an immunogenic inflammatory reaction--uveitis, associated with excessive levels of prostaglandin E2 (PGE2), and treated for prolonged periods with corticosteroids, known for their inhibitory effect on prostaglandins (PGs) production. In order to assess whether this drug retains its inhibitory effect during chronic use, we investigated the effect of long-term systemic administration of corticosteroids on PGE2 release by the choroid and retina of rabbits' eyes. We used eyes traumatized by laser irradiation, in which the inflammatory reaction is associated with an enhanced PGE2 in vitro release by the choroid-retina throughout a 2-week period; levels peaked on days 1 and 7 to values 2.2- and 5.5-fold, respectively, greater than baseline. Systemic corticosteroid administration to laser-exposed rabbits curtailed the excessive PGE2 release during the first post-laser week; later the amounts released progressively increased to levels 5.5-fold higher than baseline (day 14), whereas in the corresponding untreated laser group, levels were significantly lower. PGE2 tissue content on days 7 and 14 in steroid-treated and untreated laser groups were similarly elevated. We conclude that during prolonged systemic corticosteroids treatment the steroidal inhibitory effect on enhanced PGE2 formation by the retina-choroid of laser injured eyes is transient; it is evident during the early phase following drug administration, whereas later excessive PGE2 release is resumed.

Animals↗

Respiratory patterns after cholecystectomy. Effects of posture and CO2 stimulation.

A marked reduction in the ratio of abdominal to rib cage motion has been observed after upper abdominal surgery. This study seeks to determine the effects on respiratory pattern of stimulation with CO2 and a change in posture from supine to semirecumbent posture (hips flexed, head of bed elevated at 30 degrees to the horizontal) in patients having undergone cholecystectomy. Canopy spirometry and respiratory inductive plethysmography were used to measure minute ventilation, tidal volume, and rib cage and abdominal motion in 14 otherwise healthy women, prior to elective cholecystectomy and on the first and third postoperative days. Preoperatively, the relative contribution of the chest wall compartment to tidal volume (Vc/VT) was increased both by moving from the supine to the semirecumbent posture and by stimulation with 4 percent inhaled CO2. On the first postoperative day, there was a reduction in abdominal motion. In contrast to what happened in the preoperative period, there was no change in the relative contribution of the rib cage and abdomen when the patients moved from the supine to semirecumbent position. With CO2 stimulation, there was a further increase in the already increased absolute tidal volume of the chest. On the third postoperative day, there was an increase in abdominal motion in the supine and sitting position and during 4 percent CO2 stimulation. These results demonstrate that the response to a change in posture and to 4 percent CO2 stimulation are markedly altered in the postoperative period by the reduction in abdominal motion.

Carbon Dioxide↗

The oxygen uptake-oxygen delivery relationship during ICU interventions.

There is much interest in the relationship between oxygen delivery and oxygen consumption in the critically ill patient. This interest is occasioned by the observation that patients with sepsis and the adult respiratory distress syndrome have a linear or "supply-dependent" relationship instead of the normally observed biphasic or "supply-independent" relationship. These relationships are only valid when subjects are at rest, since during exercise, as VO2 increases, so do DO2 and the oxygen extraction ratio (ER, VO2/DO2). We examined the VO2-DO2 relationship in a group of 16 mechanically-ventilated surgical ICU patients while they were at rest and during activities that increase VO2. At low levels of activity, where mean VO2 increased from 207 +/- 38 (SD) ml/min at rest to 241 +/- 44 ml/min, there were significant increases in mean DO2 but not mean ER. With the greater (greater than 50 percent) increases in VO2 seen with chest physical therapy, there were increases in both DO2 and ER. When the VO2-DO2 relationship during low levels of exercise and rest are plotted, a linear pattern emerges that could be misinterpreted as a "supply dependent" pattern. Therefore, it is important to pay close attention to the activity state of a patient when examining the VO2-DO2 relationship.

Aged↗

Continual trending of Fick variables in the critically ill patient.

We continually monitored components of the Fick equation (oxygen consumption, arterial and mixed venous oxygen saturation) simultaneously in ten hemodynamically stable, mechanically ventilated postoperative patients in order to evaluate our ability to continually calculate cardiac output (Qc) from its Fick determinants. Qc underestimated (p less than 0.001) cardiac output calculated from intermittent CO-oximeter measurements (6.2 vs 6.4 L/min) with good correlation (r = .96), while it consistently overestimated (p less than 0.05) thermodilution cardiac output (Qtd) (6.2 vs 5.9 L/min, r = .84). Measured oxygen consumption correlated with Qtd (r = .78) nearly as well as did Qc, while mixed venous oxygen saturation correlated poorly with Qtd (r = -.10). Trends of multiple Fick variables were helpful in interpreting changes in a single parameter. We conclude that continual trending of Fick variables in critically ill patients is both feasible and useful and that Qc agrees well with both traditional Fick cardiac output computed from CO-oximetry data and thermodilution measurements. Finally, measured oxygen consumption, available continuously, correlates well with changes in cardiac output in this subset of critically-ill patients.

Adult↗

Different pathways mediate virus inducibility of the human IFN-alpha 1 and IFN-beta genes.

Multimerization of GAAANN generates sequences frequent in virus-inducible promoters. We distinguished different types of (GAAANN)4 sequences mediating virus inducibility. Type I (NN = GT, GC, CT, or CC) responds to IFNs and to IRF-1 and causes silencing. Type II (NN = TG) and type III (NN = CG) neither silence nor respond to IRF-1 or IFN. Type III mediates constitutive transcription and binds the constitutive IEFga factor, whereas type II binds the novel "TG protein". IFN-beta and IFN-alpha 1 promoters contain different response elements: The former has a type I-like sequence (PRDI) and an NF-kappa B-binding sequence (PRDII); the latter has a type II-like "TG sequence" and possibly additional elements but does not bind NF-kappa B. Type I, type II, and NF-kappa B elements represent three distinct terminal pathways mediating virus induction.

Animals↗

Low-energy laser irradiation--a new measure for suppression of arachidonic acid metabolism in the optic nerve.

Helium-neon low-energy laser (LEL) irradiation, known for its therapeutic effects in arthritis, wound healing, and muscular strain, was applied to eyes of rats that had sustained an optic nerve crush injury. Crush injury to the optic nerve resulted in a long-lasting in vitro elevation of prostaglandin E2 (PGE2) production (1.8-3.9-fold above control values during the 12 day study period). LEL irradiation per se had no effect in vitro on PGE2 production by the optic nerve; however, LEL irradiation of eyes with crushed optic nerve inhibited the enhanced production of PGE2 and leukotriene B4 in vitro by 55% and 75% during the late and immediate phase after trauma, respectively. Our findings of the suppressive effect of LEL irradiation on arachidonic acid metabolism are reminiscent of the actions of steroidal and nonsteroidal anti-inflammatory drugs, and might indicate, for the first time, the possible biochemical mechanisms associated with the clinical anti-inflammatory effects of LEL irradiation.

Animals↗

The correlation between excessive vitreal protein levels, prostaglandin E2 levels, and the blood retinal barrier.

Changes in vitreal protein and prostaglandin E2 (PGE2) concentrations, as well as chorioretinal in vitro PGE2 production, were studied in rabbit eyes following Neodymium (Nd):YAG laser retinal exposure. Laser exposure was associated with an enhanced vitreal PGE2 concentration throughout a two-week observation period, with highest levels on days 1 and 7 after exposure (a 5.3 and 4.7 increase above baseline, respectively). A transitory 50% elevation above baseline in vitreal protein levels was observed in the laser-exposed eyes during the second week after exposure. Laser exposure was also associated with an enhancement in the in vitro chorioretinal PGE2 production, which varied throughout the observation period, and was more pronounced during the first week after exposure, when levels were four times higher than baseline. Initially PGE2 vitreal levels were closely related to excessive in vitro production. However, during the second week after exposure, evidence of such correlation was lacking, but PGE2 vitreal levels coincided with a small increase in vitreal protein levels. It is suggested that disruption of the blood retinal barrier by the long-term exposure to mildly elevated vitreal PGE2 levels was accountable for protein leakage, which might have affected PGE2 removal mechanisms.

Animals↗

Integration of quality assurance activities into a computerized patient data management system in an intensive care unit.

A prototype computer-based patient data management system (PDMS) was developed for a surgery-anesthesiology intensive care unit (ICU) to reduce the time and staff needed to implement quality assurance (QA) functions. Goals of the system were to make QA functions routine and minimally intrusive to the daily operation of the ICU. PDMS collects general data (eg, admissions and discharges, lengths of stay, and bed utilization rates) and specialized data (eg, specific indicators) unique to the ICU and performs prospective monitoring for the occurrence of specific events (occurrence screening) and retrospective examinations of patient records (targeted reviews). Preliminary results suggest that PDMS facilitates the acquisition and analysis of QA data and reduces the time needed to acquire these data. Research to validate these claims and efforts to improve and expand the prototype system with a permanent production system are in progress.

Analgesics↗

The metabolic response to stress: an overview and update.

Recent investigation has demonstrated that the response to stress is mediated by complex interactions between the nervous, endocrine, immune, and hematopoietic systems. Not only is the neuroendocrine system operative but monokines and lymphokines, such as IL-1, IL-6, and TNF, also play important roles. The discovery of these mediators, along with that of macrophage-derived substances that operate at the local wound level, such as platelet-derived, basic fibroblast, transforming, and epidermal growth factors, coupled with advances in molecular biology portends much for the future. The ability to alter the endocrine response with techniques such as epidural anesthesia, the ability to specifically block certain aspects of the response (e.g., with adrenergic and prostaglandin antagonists), and the ability to synthesize potential beneficial mediators with recombinant DNA techniques (e.g., GH) may allow for modulating the response to decrease debility and complications.

Anesthesia↗

Prostanoids in the vitreous of diabetic and nondiabetic human eyes with retinal detachment.

We measured prostaglandin E2 (PGE2) and prostacyclin levels in the vitreous bodies of 5 eyes of patients with diabetic retinopathy complicated by rhegmatogenous retinal detachment (RRD) and compared them with the corresponding levels in 9 nondiabetic eyes with the same condition as well as with 10 control eyes of deceased patients with no known ocular pathology. We also studied the effect of surgical retinal reattachment on vitreal PGE2 and prostacyclin levels in 4 eyes. Vitreal samples from both nondiabetic and diabetic eyes with RRD were obtained during vitrectomy, while samples from deceased subjects (controls) were obtained 2-6 h after death. Vitreal PGE2 and prostacyclin levels in the control eyes approximated plasma levels (79.9 +/- 20.5 and 124.5 +/- 38.5 pg/ml, means +/- SD, respectively), while RRD in the nondiabetic eyes was associated with increased levels of both PGE2 and prostacyclin (3,170 +/- 3,024 and 467 +/- 283 pg/ml, respectively). In the diabetic eyes with diabetic retinopathy complicated by RRD, all of which underwent retinal photocoagulation, PGE2 and prostacyclin levels were 2-4 times lower than those of the nondiabetic eyes with detached retina. Following surgical retinal reattachment, vitreal levels of both components in diabetics and nondiabetics showed a reduction suggesting that the surgical procedure for obtaining vitreal samples was not the cause for elevated prostaglandin levels in the eyes with detached retina. We showed that RRD is associated with an excessive accumulation of PGE2 and prostacyclin in the vitreous, which is higher in nondiabetic than in diabetic eyes, indicating that diabetic retinopathy in laser-treated eyes might lead to reduced vitreal levels of these metabolites.

Adult↗

Comparison of the effects of argon and neodymium:YAG laser iridotomy on prostaglandin E2 and blood-aqueous barrier disruption.

We compared in rabbits the effects of laser iridotomy by either argon or neodymium (Nd):YAG laser on prostaglandin E2 (PGE2) production by the iris/ciliary body, its accumulation in the aqueous humor and the aqueous protein levels. PGE2 production by the iris/ciliary body, following exposure to argon or Nd:YAG laser, was similarly enhanced, with peak levels of 22.8 +/- 4.7 and 24.1 +/- 8.2 ng/mg, respectively. An increase in aqueous PGE2 levels was more pronounced in the argon as compared with the Nd:YAG group, with peak levels of 56.7 +/- 17.3 and 20.0 +/- 7.7 ng/ml, respectively. PGE2 production correlated well with aqueous PGE2 levels in the argon group, but not in the Nd:YAG group. Protein accumulated in the aqueous humor following irradiation by both types of laser light, with higher levels occurring in the argon group. These results are indicative of possible differences in the extent of the inflammatory reaction induced by the application of argon and Nd:YAG laser light to the iris.

Animals↗

Diaphragmatic breathing maneuvers and movement of the diaphragm after cholecystectomy.

Coached efforts at diaphragmatic breathing were assessed as a means of increasing diaphragmatic movement in postoperative patients. Inductive plethysmography was used to measure compartmental tidal volumes of the abdomen (Vab) and the chest (Vc) in eight women (aged 41 +/- 16 years) who had no history of cardiovascular or pulmonary disease. These patients were studied before and after (POD1,3) elective cholecystectomy. In preoperative studies, DB increased the supine value of Vab. The corresponding increase on POD1 represents a similar proportion of the resting value. The postoperative fall in resting and stimulated values of Vab is attributed to the known effects of abdominal surgery on diaphragmatic movement. Hence, DB warrants investigation as a method of prophylaxis against the pulmonary complications of surgery, because diaphragmatic movement is largely responsible for ventilation of the lower lung fields, where atelectasis and infection occur most often.

Adult↗

Corticosteroid treatment of laser retinal damage affects prostaglandin E2 response.

The current study investigated the effect of steroid treatment of eyes subjected to a single retinal argon laser lesion on vitreal accumulation of both prostaglandin E2 (PGE2) and protein and their relationship with the amounts of PGE2 released from the retina-choroid. Laser exposure resulted in an elevation in the amounts of PGE2 released by the retina-choroid of laser-treated eyes: there was an initial peak on day 1, followed by a higher peak on day 7 (13.0 +/- 3.9 ng/mg protein and 32.9 +/- 4.9 ng/mg protein, respectively) after which levels progressively declined. Steroid treatment prevented the initial peak, but did not prevent the enhanced PGE2 amounts released during the second week. Thus, on day 7 the amounts released were lower by 32% than in the untreated group (21.0 +/- 8.6 ng/mg protein vs 32.9 +/- 4.9 ng/mg protein, P = 0.000); by day 14, however, peak values in the treated group were higher than in the untreated group (32.2 +/- 12.4 ng/mg protein and 10.6 +/- 4.5 ng/mg protein, respectively). In steroid-treated eyes, vitreal PGE2 concentration remained unchanged from baseline over a 2-week follow-up, whereas in the untreated laser group, levels peaked on day 7 to 10.7 +/- 3.6 ng/ml, exceeding baseline levels of 5.8 +/- 1.7 ng/ml (P = 0.0002). Laser exposure was also associated with a biphasic elevation in vitreal protein concentrations on days 3 and 14 (0.68 +/- 0.16 mg/ml and 0.79 +/- 0.13 mg/ml, respectively); these were significantly higher than the baseline value of 0.43 +/- 0.12 mg/ml (P = 0.03 and P = 0.004, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Submaximal exercise in emphysema and malnutrition at two levels of carbohydrate and fat intake.

Eight malnourished patients with emphysema (EMPH) and eight malnourished patients without evidence of lung disease (MLAN) received an infusion of 5% dextrose plus electrolytes (D5W) for 48 h and were then randomly assigned to a hypercaloric diet with either 53% of the calories as carbohydrate (CB) or with 55% as fat (FB) for the 1st wk, maintaining a constant protein intake. The alternate diet was given the following week. Ventilation and gas exchange were measured during supine cycle ergometry at 0, 12, and 25 W during the D5W, CB, and FB diet periods. At each exercise intensity, the EMPH group demonstrated a 12-15% greater O2 consumption, a lower respiratory quotient, and an O2 debt larger than that of the MALN group. Resting ventilation was higher during the CB than FB regimen in both groups of patients, but during the CB diet the EMPH group had a more exaggerated ventilatory response than the MALN group. The results demonstrate that EMPH patients have an unusual metabolic pattern during hypercaloric feeding and exercise. Furthermore in EMPH patients a FB regimen does not appear to create the additional stress on the respiratory system during exercise that is generated with a CB regimen.

Adult↗

Effects of parenteral amino acid nutritional regimens on oxidative and conjugative drug metabolism.

Our goals were to determine the time-course of the increase in oxidative drug metabolism that occurs when parenteral nutrition is changed from dextrose to amino acids (23% branched-chain), whether the composition of the amino acid regimen influences this effect, and whether drug conjugation is similarly altered. We examined in healthy volunteers the effects of changing isocalorically from intravenous dextrose 440 kcal/day to amino acids, on one occasion 23% branched-chain and on another 85%. The change to the 23% regimen produced a significant increase in metabolic clearance of antipyrine, a model for oxidation (mean +/- SE 3.0 +/- 0.3 to 3.7 +/- 0.4 L/h, N = 6, P less than 0.003), but the change to the 85% regimen did not, indicating that the composition of an amino acid infusion can influence its effect on oxidative metabolism. Analysis of the concentration-time curve for antipyrine after simultaneous dosing and start of the 23% regimen suggests that the increase in metabolic capacity occurred within a few hours. Metabolic clearance of acetaminophen, a model for conjugation, was not altered by changing to either amino acid regimen.

Acetaminophen↗

Effect of incentive spirometry on diaphragmatic function after surgery.

Many of the alterations in lung function that occur after upper abdominal surgery are attributable to reduced diaphragmatic activity. This study was undertaken to determine whether incentive spirometry produces a voluntary activation of diaphragmatic movement in patients with postoperative diaphragmatic dysfunction. Inductance plethysmography was used to measure the tidal volumes of the abdomen and chest in eight women before cholecystectomy and on the first and third postoperative days. In resting patients the relative contribution of the abdominal compartment decreased from 0.520 +/- 0.100 preoperatively to 0.274 +/- 0.265 on postoperative day 1 (p less than 0.01), reflecting the effect of surgery on diaphragmatic function. Inspiratory flow (an index of inspiratory drive) was unaltered by surgery during both resting and incentive spirometry breaths, despite changes in tidal volume. Preoperatively, incentive spirometry increased the tidal volume of the abdominal compartment from 141 +/- 26 ml to 285 +/- 188 ml (p less than 0.005) as a result of increased diaphragmatic movement. This effect was not seen postoperatively; instead, postoperative patients responded to incentive spirometry by increasing the tidal excursion of the chest compartment (158 +/- 37 to 630 +/- 253, p less than 0.005), without any increase in abdominal tidal volume. Thus, incentive spirometry failed to increase diaphragmatic movement in postoperative patients.

Abdomen↗