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Biomedical subjects

D S Prough

Publications and source records attributed to D S Prough.

At least 19 recordsLinked to original sources
PubMed2006

Concentrations of extracellular free zinc (pZn)e in the central nervous system during simple anesthetization, ischemia and reperfusion.

"Free Zn2+" (rapidly exchangeable Zn2+) is stored along with glutamate in the presynaptic terminals of specific specialized (gluzinergic) cerebrocortical neurons. This synaptically releasable Zn2+ has been recognized as a potent modulator of glutamatergic transmission and as a key toxin in excitotoxic neuronal injury. Surprisingly (despite abundant work on bound zinc), neither the baseline concentration of free Zn2+ in the brain nor the presumed co-release of free Zn2+ and glutamate has ever been directly observed in the intact brain in vivo. Here, we show for the first time in dialysates of rat and rabbit brain and human CSF samples from lumbar punctures that: (i) the resting or "tonic" level of free Zn2+ signal in the extracellular fluid of the rat, rabbit and human being is approximately 19 nM (95% range: 5-25 nM). This concentration is 15,000-fold lower than the "300 microM" concentration which is often used as the "physiological" concentration of free zinc for stimulating neural tissue. (ii) During ischemia and reperfusion in the rabbit, free zinc and glutamate are (as has often been presumed) released together into the extracellular fluid. (iii) Unexpectedly, Zn2+ is also released alone (without glutamate) at a variable concentration for several hours during the reperfusion aftermath following ischemia. The source(s) of this latter prolonged release of Zn2+ is/are presumed to be non-synaptic and is/are now under investigation. We conclude that both Zn2+ and glutamate signaling occur in excitotoxicity, perhaps by two (or more) different release mechanisms.

Anesthetics↗
PubMed2005

Analysis of long-term gene expression in neurons of the hippocampal subfields following traumatic brain injury in rats.

After experimental traumatic brain injury (TBI), widespread neuronal loss is progressive and continues in selectively vulnerable brain regions, such as the hippocampus, for months to years after the initial insult. To clarify the molecular mechanisms underlying secondary or delayed cell death in hippocampal neurons after TBI, we compared long-term changes in gene expression in the CA1, CA3 and dentate gyrus (DG) subfields of the rat hippocampus at 24 h and 3, 6, and 12 months after TBI with changes in gene expression in sham-operated rats. We used laser capture microdissection to collect several hundred hippocampal neurons from the CA1, CA3, and DG subfields and linearly amplified the nanogram samples of neuronal RNA with T7 RNA polymerase. Subsequent quantitative analysis of gene expression using ribonuclease protection assay revealed that mRNA expression of the anti-apoptotic gene, Bcl-2, and the chaperone heat shock protein 70 was significantly downregulated at 3, 6 (Bcl-2 only), and 12 months after TBI. Interestingly, the expression of the pro-apoptotic genes caspase-3 and caspase-9 was also significantly decreased at 3, 6 (caspase-9 only), and 12 months after TBI, suggesting that long-term neuronal loss after TBI is not mediated by increased expression of pro-apoptotic genes. The expression of two aging-related genes, p21 and integrin beta3 (ITbeta3), transiently increased 24 h after TBI, returned to baseline levels at 3 months and significantly decreased below sham levels at 12 months (ITbeta3 only). Expression of the gene for the antioxidant glutathione peroxidase-1 also significantly increased 6 months after TBI. These results suggest that decreased levels of neuroprotective genes may contribute to long-term neurodegeneration in animals and human patients after TBI. Conversely, long-term increases in antioxidant gene expression after TBI may be an endogenous neuroprotective response that compensates for the decrease in expression of other neuroprotective genes.

Animals↗
PubMed2001

Intraischemic mild hypothermia increases hippocampal CA1 blood flow during forebrain ischemia.

The hippocampal CA1 sector is selectively vulnerable to forebrain ischemia but protected by mild hypothermia. However, the consequence of intraischemic hypothermia on CA1 blood flow during the insult has not been adequately characterized. The effects of mild intraischemic hypothermia on relative changes in regional hippocampal CA1 blood flow were recorded continuously using laser Doppler flowmetry (LDF) during and 30 min after 6 min of forebrain ischemia. Six experimental groups (n=6/group) of fasted male Wistar rats were compared. Groups 1, 3 and 5 consisted of normothermic rats that underwent either 6 (for CBF measurements) and 6 or 10 (for 7 day survival-CA1 neuronal death measurements) min of transient forebrain ischemia using bilateral carotid clamping and hemorrhagic hypotension. Groups 2, 4 and 6 rats were subjected to mild hypothermia (34 degrees C) before, during, and 30 min after 6 (for CBF measurements) and 6 or 10 (for 7 day survival-CA1 neuronal death measurements) min of transient forebrain ischemia. CA1 blood flow and electroencephalogram (EEG) were continuously recorded. During the ischemic insult there were intergroup differences in the magnitude of CBF decreases in the CA1 region. In both groups 1 and 2, CBF returned to preischemic values within 1 min of reperfusion but hypothermic rats had more sustained hyperemia. Hypothermic rats had a quicker recovery of EEG activity and less delayed CA1 neuronal death (group 2 versus 4). These data suggest ischemic blood flow to the CA1 sector was altered by intraischemic mild hypothermia which may contribute to the greater benefit of intraischemic hypothermic neuroprotection.

Animals↗
PubMed2001

Designing meaningful industry metrics for clinical productivity for anesthesiology departments.

IMPLICATIONS: Clinical productivity measurements that account for differences in clinical settings and concurrencies provided more precise comparisons between two anesthesiology groups. The data show that different concurrencies confound the current industry standard, "per full-time equivalent" measurements, whereas "per operating room site" and "per case" measurements allowed for more meaningful comparisons.

Anesthesiology↗
PubMed2001

The dynamics of vascular volume and fluid shifts of lactated Ringer's solution and hypertonic-saline-dextran solutions infused in normovolemic sheep.

UNLABELLED: Infusions of hyperosmotic-hyperoncotic solutions such as hypertonic saline dextran (HSD) are used in Europe for resuscitation of traumatic shock and perioperative volume support as an adjunct to conventional isotonic crystalloids. Whereas plasma volume expansion of HSD has been measured at single time points after the intravascular volume expansion, the detailed time course of fluid shifts during and after infusions have not been reported. We compared the time course of volume expansion during and after 30-min infusions of 4 mL/kg HSD and 25 mL/kg lactated Ringer's solution (LR) in normovolemic conscious splenectomized sheep. Peak plasma volume (Evans blue and hemoglobin dilution) expansion was similar for HSD (7.8 +/- 0.9 mL/kg) and the larger sixfold volume of LR (7.2 +/- 0.5 mL/kg). However, 30 min after the 30-min infusion (T60), plasma expansion remained larger after HSD (5.1 +/- 0.9 mL/kg) than after LR (1.7 +/- 0.6 mL/kg). Both solutions caused an equivalent diuresis. Intravascular volume expansion efficiency (VEE), defined as milliliter plasma expansion/milliliter fluid infused at 0 (T30), 30 (T60), and 60 (T90) min after infusion ended was 1.8, 1.3, and 0.8, respectively for HSD, whereas LR provided a VEE of only 0.27, 0.07, and 0.07. The relative expansion efficiency of HSD versus LR, calculated as the ratio (VEE(HSD)/VEE(LR)), was 7-fold that of LR at the end of infusion T30, and 20-fold at T60, but decreased to 9-fold by T120. Intravascular volume dynamic studies of different volume expanders in animals and patients may provide anesthesiologists with a new tool for monitoring the effectiveness of fluid therapy. IMPLICATIONS: Hypertonic saline dextran (HSD) is a new plasma expander recently approved for clinical use in Europe. We compared the plasma volume expansion of HSD versus lactated Ringers (LR) in normovolemic sheep. After a 30 min infusion, HSD was 7 times as effective at expanding volume as an equal volume of LR, but for the next 90 minutes the relative effectiveness of HSD increased to 10-20 times.

Algorithms↗
PubMed2001

The impact of longer-than-average anesthesia times on the billing of academic anesthesiology departments.

UNLABELLED: Academic anesthesiology departments provide clinical services for surgical procedures that have longer-than-average surgical times and correspondingly increased anesthesia times. We examined the financial impact of these longer times in three ways: 1) the estimated loss in revenue if billing were done on a flat-fee system by using industry-averaged anesthesia times; 2) the estimation of incremental operating room (OR) sites necessitated by longer anesthesia times; and 3) the estimated potential gain in billed units if the hours of productivity of current anesthesia time were applied to surgical cases of average duration. Health Care Financing Administration average times per anesthesia procedure code were used as industry averages. Billing data were collected from four academic anesthesiology departments for 1 yr. Each claim billed with ASA units was included except for obstetric anesthesia care. All clinical sites that do not bill with ASA units were excluded. Base units were determined for each anesthesia procedure code. The mean commercial conversion factor (US$45 per ASA unit) for reimbursement was used to estimate the impact in dollar amounts. In all four groups, anesthesia times exceeded the Health Care Financing Administration average. The loss per group in billed ASA units if a flat-fee billing system were used ranged from 18,194 to 31,079 units per group, representing a 5% to 15% decrease (estimated billing decrease of US$818,719 to US$1,398,536 per group). The number of excess OR sites necessitated by longer surgical and anesthesia times ranged from 1.95 to 4.57 OR sites per group. The potential gain in billed units if the hours of productivity of current anesthesia time were applied to surgical cases of average duration was estimated to be from 13,273 to 21,368 ASA units. Longer-than-average anesthesia and surgical times result in extra hours or additional OR sites to be staffed and loss of potential reimbursement for the four academic anesthesiology departments. A flat-fee system would adversely affect academic anesthesiology departments. IMPLICATIONS: We examined the economic impact of longer-than-average anesthesia times on four academic anesthesiology departments in three ways: the estimated loss in revenue under a flat-fee system, the excess operating room sites staffed, and the potential gain in revenue if the surgeries were of average length. These results should be considered both in productivity measurements and strategies for operating room management.

Accounting↗
PubMed2001

Peroxynitrite reduces vasodilatory responses to reduced intravascular pressure, calcitonin gene-related peptide, and cromakalim in isolated middle cerebral arteries.

Vasodilatory responses to progressive reductions in intravascular pressure or to calcitonin gene-related peptide (CGRP) or cromakalim were determined in rodent middle cerebral arteries (MCAs) before and after treatment with peroxynitrite (ONOO-). Middle cerebral artery diameters in isolated, pressurized MCAs were measured as intravascular pressure was reduced from 100 to 20 mm Hg in 20-mm Hg increments before and after inactive ONOO-, pH-adjusted ONOO-, or 10, 20, or 40 micromol/L ONOO- was added to the bath. In other MCAs, responses to CGRP (1 x 10-9 - 5 x 10-8) or cromakalim (3 x 10-8 - 8 x 10-7) were measured before and after the addition of 25 micromol/L ONOO-. Inactive ONOO- (n = 6, P = 0.40), pH-adjusted ONOO- (n = 6, P = 0.29), and 10 micromol/L ONOO- (n = 6, P = 0.88) did not reduce vasodilatory responses to reduced intravascular pressure. Middle cerebral arteries treated with 20 (n = 6, P < 0.0001) and 40 (n = 6, P > 0.0001) micromol/L ONOO- constricted significantly when intravascular pressure was reduced. Vasodilatory responses to CGRP or cromakalim were reduced by ONOO- (P > 0.02, n = 6 and P > 0.01, n = 7, respectively). ONOO- had no effect on vasoconstriction in response to serotonin or vasodilation in response to KCl. These studies demonstrate that ONOO- reduces multiple cerebral vasodilatory responses.

Animals↗
PubMed2000

Physiologic acid-base and electrolyte changes in acute and chronic renal failure patients.

Patients with acute and chronic renal failure are vulnerable to a wide variety of acid-base and electrolyte disturbances. The variety is related not only to predictable disturbances that arise as a consequence of impaired urinary excretion, but also to associated factors, such as intercurrent disease processes, chronic medications, and renal replacement therapy. This article emphasizes the pathogenesis, diagnosis, and treatment of common problems, including metabolic acidosis, hyponatremia, hypernatremia, hyperkalemia, hyperphosphatemia, and hypocalcemia.

Acid-Base Imbalance↗
PubMed2000

Measurement of individual clinical productivity in an academic anesthesiology department.

BACKGROUND: The ability to measure productivity, work performed, or contributions toward the clinical mission has become an important issue facing anesthesiology departments in private practice and academic settings. Unfortunately, the practice and billing of anesthesia services makes it difficult to quantify individual productivity. This study examines the following methods of measuring individual productivity: normalized clinical days per year (nCD/yr); time units per operating-room day worked (TU/OR day); normalized time units per year (nTU/yr); total American Society of Anesthesiologists (ASA) units per OR day (tASA/OR day); and normalized total ASA units per year (ntASA/yr). METHODS: Billing and scheduling data for clinical activities of faculty members of an anesthesiology department at a university medical center were collected and analyzed for the 1998 fiscal year. All clinical sites and all clinical faculty anesthesiologists were included unless they spent less than 20% of their time during the fiscal year providing clinical care, i.e., less than 0.2 clinical full-time equivalent. Outliers, defined as faculty who had productivity greater or less than 1 SD from the mean, were examined in detail. RESULTS: Mean and median values were reported for each measurement, and different groups of outliers were identified. nCD/yr identified faculty who worked more than their clinical full-time equivalent would have predicted. TU/OR day and tASA/OR day identified apparently low-productivity faculty as those who worked a large portion of their time in obstetric anesthesia or an ambulatory surgicenter. tASA/OR day identified specialty anesthesiologists as apparently high-productivity faculty. nTU/yr and ntASA/yr were products of the per-OR day measurement and nCD/yr. CONCLUSION: Each of the measurements studied values certain types of productivity more than others. By defining what type of service is most important to reward, the most appropriate measure or combination of measures of productivity can be chosen. In the authors' department, nCD/yr is the most useful measure of individual productivity because it measures an individual anesthesiologist's contribution to daily staffing, includes all clinical sites, is independent of nonanesthesia factors, and is easy to collect and determine.

Anesthesia Department, Hospital↗