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William L Lanier

Publications and source records attributed to William L Lanier.

At least 19 recordsLinked to original sources
PubMed2006

The relationship of retinal VEGF and retinal IGF-1 mRNA with neovascularization in an acidosis-induced model of retinopathy of prematurity.

PURPOSE: Acidosis-induced retinopathy (AIR) in the neonatal rat provides an alternative model for retinopathy of prematurity (ROP). We studied the relationship of vascular endothelial growth factor (VEGF) retinal mRNA and insulin-like growth factor-1 (IGF-1) retinal mRNA expression with the emergence of neovascularization (NV) in AIR. METHODS: Two hundred seventy-five newborn Sprague-Dawley rats were raised in 11 expanded litters of 25. Using our established AIR model, acidosis was induced by twice-daily gavage with NH4Cl from day 2 to day 8 of life (n=175). Rats were sacrificed at days 5, 8, and 10. Nongavaged rats were used as age-matched controls (n=100). Retinae from left eyes were dissected, flatmounts were ADPase-stained, and the presence and severity of NV was scored in a masked manner. Individual right retinae were processed for analysis of retinal VEGF and IGF-1 mRNA using quantitative real-time reverse-transcriptase PCR (qRT-PCR). RESULTS: Retinal VEGF mRNA was increased 1.4-fold at day 10 in AIR, when compared with age-matched controls (p=0.03). This correlated with maximal NV at day 10 in AIR. Retinal IGF-1 mRNA was decreased to 82% of its normal expression on day 8 (p=0.006), prior to maximal NV, before returning to normal expression at day 10, when compared with nonacidotic controls. CONCLUSIONS: In AIR, preretinal neovascularization is associated with decreased retinal IGF-1 mRNA prior to maximal NV and increased retinal VEGF mRNA at the time of maximal NV. These growth factor changes in AIR are similar to those seen with hypercarbic oxygen-induced retinopathy. The retinal IGF-1 pathway may provide an alternative target for therapeutic intervention in abnormal retinal angiogenesis.

Acidosis↗
PubMed2006

A three-decade perspective on anesthesia safety.

Modern medical practice, and particularly that within the hospital environment, has been under intense scrutiny in an attempt to improve patient safety and optimize outcomes. Anesthesiology has been cited as among the most successful specialties effecting improvements. According to the Institute of Medicine's 1999 report, To Err is Human, "... anesthesiology has successfully reduced anesthesia mortality rates from two deaths per 10,000 anesthetics administered, to one death per 200,000 to 300,000 anesthetics administered." The current report reviews representative highlights from 30 years of progress in improving anesthesiology safety and offers a speculative synthesis of the factors critical to past and future successes. The seven identified points include 1) the emergence of a champion and his allies, 2) initial efforts to identify and quantify broad-reaching problems, 3) research addressing intellectually "amusing" problems of relevance to practitioners, 4) reaching out to others with focused expertise in problem prevention and problem solving, 5) sharing the responsibility for quality and safety improvement with other specialties, 6) expanding buy-in and participation within the anesthesia community, and 7) preparing for the future. The factors provide not only an accounting of anesthesiologists' successes, but also a road map for other groups and specialties desiring to emulate the anesthesiologists' experience.

Anesthesia↗
PubMed2005

Anti-thyroid methimazole in an acidosis-induced retinopathy rat model of retinopathy of prematurity.

PURPOSE: Methimazole (MMI), an anti-thyroid drug known to reduce serum levels of L-thyroxine (T4) and insulin-like growth factor-1 (IGF-1), has been previously reported to increase the incidence of neovascularization (NV) in an oxygen-induced retinopathy (OIR) model of retinopathy of prematurity (ROP) in rats. We investigated the effect of MMI on the incidence and severity of NV in a non-oxygen-induced model of ROP, acidosis-induced retinopathy (AIR). METHODS: Newborn Sprague Dawley rats were raised in expanded litters of 25 in room air for four or ten days under one of the two following conditions: (1) Our established model of AIR (acidosis via NH4Cl gavage (10 mmol/kg) twice daily from days 2 to 7, followed by two days of recovery) or (2) MMI (given as a 0.1% solution to nursing mothers) in the above AIR model. Left eyes were fixed, and retinas were dissected and ADPase-stained. Flat mounted retinas were graded in a masked manner for presence and severity of NV, and retinal vascular areas were quantified. Serum IGF-1 and T4 concentrations were measured by radioimmunoassay on days 4 and 10. Arterial blood pH measurements were performed on day 4. RESULTS: The incidence and severity of NV were similar between AIR and MMI-AIR rats (incidence: 24% and 33%). Serum IGF-1 concentrations in 10 day MMI-AIR rats were significantly lower than untreated non-acidotic controls (medians: 158 ng/ml and 207 ng/ml; p=0.03). Serum IGF-1 concentrations were similar between 10 day AIR rats and untreated non-acidotic controls (medians: 189 ng/ml and 207 ng/ml; p>0.9). CONCLUSIONS: MMI does not increase the incidence or severity of NV in an AIR neonatal rat model of ROP. Although serum IGF-1 has been considered permissive for NV in immature retinas, supranormal concentrations of serum IGF-1 may not be necessary for abnormal retinal angiogenesis. Further studies are warranted on the roles of serum IGF-1 and L-thyroxine in the pathogenesis of ROP.

Acidosis↗
PubMed2005

An overview of transforming changes at Mayo Clinic Proceedings during 2005.

For the past 6 years, the Editorial Board and staff of Mayo Clinic Proceedings have dedicated ourselves to the progressive evolution of this journal. During this period, and for the foreseeable future, we have embraced change and improvement as themes for our daily efforts. As such, the changes identified in this communication are not a leap forward for the journal, they merely represent the next logical step in the growth of the journal. Given the momentum that has developed during the past few years, readers should expect to see further changes, all intended to better communicate with our principal readers, practicing physicians. In the final analysis, we are driven by a rededication of the journal to the primary value of Mayo Clinic: "The needs of the patient come first." While the journal's leadership has long looked to this statement for guidance, our approach to addressing this value in 2005 will require a considerable number of innovations. We look forward to sharing with you, our readers, these next steps in the journal's history. We trust that we will be able to learn and grow together so that, in the final analysis, the journal will build on its reputation as an authoritative and respected source of information.

Electronic Mail↗
PubMed2005

Resource utilization and outcome in gravely ill intensive care unit patients with predicted in-hospital mortality rates of 95% or higher by APACHE III scores: the relationship with physician and family expectations.

OBJECTIVE: To assess resource utilization and outcome in gravely ill patients admitted to an intensive care unit (ICU) and the potential association with health care workers' and family members' expectations. PATIENTS AND METHODS: We retrospectively evaluated ICU patients with a predicted in-hospital mortality rate of 95% or higher (PM95) using the Acute Physiology and Chronic Health Evaluation III (APACHE III) on 2 consecutive days. All patients were admitted to a single institution between September 30, 1994, and August 9, 2001. RESULTS: The APACHE III database contained data from 38,165 ICU patients during the study interval. Of these, 248 (0.65% of ICU admissions) achieved PM95 status and were included in the study. Between PM95 and hospital discharge, resource utilization (eg, blood transfusion, hemodialysis, surgery, and computed tomography or magnetic resonance imaging) was extensive. A total of 23% of patients survived to hospital discharge, yet all but 1 were moderately or severely disabled. One year after achieving PM95, 10% (95% confidence interval, 7%-15%) of patients were alive. For 229 patients, the medical records contained physician documentation that indicated a likely fatal outcome. Thirty-six of these medical records documented unrealistic family expectations of a good outcome. The latter finding correlated with increased resource utilization without significant improvement in 1-year survival. In contrast, absence of physician documentation of a likely fatal outcome In 19 patients correlated with an improved likelihood of hospital (74%) and 1-year (47%) survival. CONCLUSION: Despite better-than-predicted survival outcomes, patient functionality and 1-year survival were poor. Unrealistic family expectations were associated with increased resource utilization without significant survival benefit, whereas absence of physician documentation of likely impending death (which correlated with improved survival) may denote the prognostication skills of experienced clinicians.

APACHE↗
PubMed2004

Effect of bicarbonate on retinal vasculature and acidosis-induced retinopathy in the neonatal rat.

BACKGROUND: Systemic acidosis induces preretinal neovascularization (NV) analogous to retinopathy of prematurity (ROP) in the neonatal rat. Sodium bicarbonate is used in human neonates to treat acidosis. The effects of alkali administration on the developing retinal vasculature and on acidosis-induced retinopathy (AIR) are unknown. We investigated the effect of sodium bicarbonate gavage on the retinal vasculature of normal and acidotic neonatal rats to determine (1) whether bicarbonate treatment is associated with preretinal NV and (2) whether AIR can be prevented with systemic bicarbonate treatment. METHODS: The extent of acidosis and alkalosis were initially determined from carotid arterial blood samples. In the bicarbonate-alone study, newborn rats were randomized into litters of 25 and received bicarbonate doses of 15 mmol/kg twice daily and 20 mmol/kg once daily from days 2 to 7. Control animals received saline gavage. In the AIR treatment study, acidosis was induced in neonatal rats by intraperitoneal injection of acetazolamide 200 mg/kg from days 2 to 7. Acetazolamide-treated rats received either additional bicarbonate gavage or no additional treatment. Eyes were enucleated on day 13, and the retinal vasculature was assessed for NV using ADPase staining techniques and light microscopy. RESULTS: Systemic alkalosis (peak pH 7.55+/-0.02; mean +/- SD) was confirmed with bicarbonate gavage, and partial reversal of acidosis was confirmed when acetazolamide-treated rats received bicarbonate. Surviving rats receiving bicarbonate 15 mmol/kg twice daily (28% survival) and 20 mmol/kg bicarbonate once daily (45% survival) had an incidence of preretinal NV of 9% and 8%, respectively. No NV was seen in saline-control rats. In the acetazolamide-treated rats, the incidence of preretinal NV in surviving rats was numerically lower in bicarbonate-treated rats than acetazolamide-only controls (8% versus 24%, p=0.065) but with only 19% survival in the bicarbonate-treated rats. CONCLUSIONS: In the neonatal rat, alkalosis induced by bicarbonate gavage is associated with a low incidence of mild, preretinal NV similar to ROP. Although treating acidotic rats with bicarbonate may reduce the incidence of preretinal NV, treatment was associated with an unacceptable mortality rate.

Acetazolamide↗
PubMed2004

The role of VEGF and IGF-1 in a hypercarbic oxygen-induced retinopathy rat model of ROP.

PURPOSE: We have previously described a severe form of oxygen-induced retinopathy (OIR) in the neonatal rat, analogous to human retinopathy of prematurity (ROP), where carbon dioxide is added to the inspired environment (hypercarbic OIR). We studied the time course of emergence and resolution of neovascularization (NV) in normocarbic OIR and hypercarbic OIR and the associated changes in VEGF and IGF-1 mRNA levels in hypercarbic OIR. METHODS: 550 newborn Sprague-Dawley rats were raised in 22 expanded litters of 25. Beginning at day 1 of life, rats were exposed to 7 daily cycles of hyperoxia (80% O2, 20.5 h) and hypoxia (10% O2, 0.5 h) with a gradual return to 80% O2 over 3 h. Inspired CO2 was maintained at 0.2% for 200 rats (normocarbic OIR) and 10% for 100 rats (hypercarbic OIR). Rats were sacrificed after a subsequent 5 day room air recovery period. An additional 250 rats raised in room air served as age matched controls. Retinae from left eyes were dissected and flatmounts were ADPase-stained. The presence and severity of NV was scored in a masked manner. Right eyes in hypercarbic OIR litters and room air controls were processed for analysis of VEGF and IGF-1 mRNA. RESULTS: In normocarbic OIR, NV started to emerge before room air recovery began at day 8. It was maximal at day 10 and resolved by day 20. In hypercarbic OIR, a similar pattern was seen, with emergence prior to day 8, peak at day 13 and resolution by day 20. In hypercarbic OIR, retinal VEGF mRNA was decreased at day 8 and increased at day 10 compared to room air controls, correlating with maximal NV. Retinal IGF-1 mRNA was not increased at any time in hypercarbic OIR compared to room air controls. CONCLUSIONS: Neovascularization resulting from normocarbic OIR or hypercarbic OIR occurs before room air recovery. Retinal VEGF mRNA was downregulated and subsequently upregulated prior to maximal NV in hypercarbic OIR. Neovascularization in the hypercarbic OIR model does not appear to be associated with increased retinal IGF-1 mRNA.

Animals↗
PubMed2004

Effect of single-dose dexamethasone on blood glucose concentration in patients undergoing craniotomy.

Dexamethasone, a corticosteroid used to treat cerebral edema, is known to produce elevations in the blood glucose concentration, but the effect of a single intraoperative dose of dexamethasone on the blood glucose concentration is unknown. Glucose concentrations in response to either a 10-mg intravenous bolus of dexamethasone or a saline placebo were evaluated in nondiabetic patients undergoing elective craniotomy. Both arterial and venous blood glucose concentrations were obtained immediately before and after treatment and hourly for 4 hours intraoperatively. The arterial blood glucose concentration in those who received 10 mg dexamethasone (n = 10) increased from 97 +/-15 mg/dL (mean +/- SD) to 149 +/- 23 mg/dL over the course of the study, compared with a change from 88 +/- 11 mg/dL to 103+/-12 mg/dL in those who received placebo (n = 10) (P < 0.05 for 4-hour sample vs. baseline for both groups; P < 0.05 between groups at 4 hours). Further, venous blood glucose concentrations were highly predictive of arterial glucose values (R = 0.98; P < 0.001). Since elevations in the blood glucose concentration should be avoided in the setting of central nervous system ischemia, findings from this investigation suggest that contemplated corticosteroid use should be reviewed for appropriateness of treatment. If dexamethasone is used, even as a single dose during craniotomy, intraoperative blood glucose concentrations should be carefully monitored and hyperglycemia treated, particularly in patients at risk for glucose-mediated exacerbation of brain injury.

Aged↗
PubMed2004

Hemodynamic responses to epinephrine-containing local anesthetic injection and to emergence from general anesthesia in transsphenoidal hypophysectomy patients.

Patients undergoing transsphenoidal pituitary surgery may experience hypertensive episodes during the intranasal injection of vasoconstrictor-supplemented local anesthetics or emergence from general anesthesia. The present research characterized the blood pressure responses during transsphenoidal surgery and tested the hypothesis that the underlying pituitary disease influences the incidence and magnitude of the blood pressure responses. The records of 100 patients were retrospectively reviewed. All had direct blood pressure measurements recorded using a computer-based anesthesia recording system. Mean age was 49 +/- 17 years (+/- SD) and 52% were male. Blood pressure increased by 60 +/- 37 mm Hg systolic and 23 +/- 22 mm Hg diastolic with intranasal injection and 42 +/- 24 mm Hg systolic and 23 +/- 16 mm Hg diastolic during emergence from general anesthesia. Systolic blood pressure increased by greater than 50% in 58% of patients following intranasal injection and in 33% of patients upon emergence from anesthesia. Blood pressure responses did not differ with respect to endocrinopathy type (Cushing's disease, acromegaly, or other pathology), gender, age, surgeon, history of prior transsphenoidal surgery, history of either hypertension or diabetes, or preoperative use of either beta-adrenergic or calcium channel-blocking drugs. There was poor correlation between the epinephrine dose injected (range 30-220 microg) and systolic blood pressure response (r = 0.24; r2 = 0.06; P = 0.031). Blood pressure increases were not associated with cardiac arrhythmias, persistent myocardial ischemia, or myocardial infarction. The authors conclude that in transsphenoidal hypophysectomy patients, large blood pressure increases are common with intranasal injection and upon awakening from general anesthesia. However, the authors were not able to find a variable that might enable the prediction of which patients are most likely to experience the most intense blood pressure elevations.

Acromegaly↗
PubMed2004

The anti-thyroid drug methimazole induces neovascularization in the neonatal rat analogous to ROP.

PURPOSE: To determine the effect of methimazole (MMI), an anti-thyroid drug known to reduce serum l-thyroxine (T4), and insulin-like growth factor (IGF)-1 concentrations, on retinal vascular development in neonatal rats. METHODS: Sprague-Dawley rats (n=175) were raised in expanded litters of 25 in room air and were exposed to MMI from birth (given as a 0.1% solution to nursing mothers for either 4 or 10 days). Experiments ended on day 4 (n=25) or 10 (n=50) of life. A third group was exposed to MMI for the initial 4 days of life and then allowed to recover for the next 6 days (n=50). Fifty control rats were analyzed on day 4 (n=25) or 10 (n=25) of life. Left eyes were fixed, and retinas were dissected and stained with adenosine diphosphatase (ADPase). Retinas were graded for presence and severity of neovascularization (NV) in a masked manner, and retinal vascular areas were quantified. In a subsequent study, serum IGF-1 and T4 levels were measured by radioimmunoassay in an additional 200 rats exposed to treatments identical to those described. RESULTS: Retinal NV occurred in 31% of rats exposed to 10 days of MMI and 4% (P=0.02) of rats exposed to 4 days of MMI, followed by 6 days of recovery. None of the rats exposed to 4 days of MMI alone and none of the control animals was graded positive for NV. Retinal vascular areas were significantly reduced in rats exposed to 4 days of MMI compared with 4-day control animals (36% +/- 6% vs. 50% +/- 6%, P=0.0001). Serum IGF-1 levels were markedly reduced in 4-day MMI rats compared with age-matched control animals (42 ng/mL vs. 133 ng/mL, P=0.0001) and in 10-day MMI rats compared with 10-day control animals (133 ng/mL vs. 206.5 ng/mL, P=0.005). Serum T4 levels were similarly suppressed in the MMI-exposed litters compared with control animals at day 10 (P=0.008). In contrast, rats exposed to 4 days of MMI followed by 6 days of recovery had normal serum IGF-1 and T4 levels by day 10. CONCLUSIONS: The anti-thyroid drug, MMI, induces NV in neonatal rats. This may be mediated by the initial suppression of serum IGF-1. Nevertheless, the lower incidence of NV when serum IGF-1 levels are initially suppressed followed by complete recovery, is contrary to a purely permissive role for serum IGF-1, as reported previously. The relationship between the temporal course of serum IGF-1 and NV in immature retinas needs further investigation.

Animals↗