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Timothy E Albertson

Publications and source records attributed to Timothy E Albertson.

14 recordsLinked to original sources
PubMed2006

Structure-activity relationship for noncoplanar polychlorinated biphenyl congeners toward the ryanodine receptor-Ca2+ channel complex type 1 (RyR1).

Ryanodine receptor isoforms are expressed in both excitable and nonexcitable tissues where they form microsomal Ca2+ release channels broadly involved in shaping cellular signaling. In this report, we provide a detailed structure-activity relationship (SAR) for polychlorinated biphenyl (PCB) congeners and metabolites necessary for enhancing ryanodine receptor type 1 (RyR1) activity using [3H]ryanodine ([3H]Ry) binding analysis. The 2,3,6-Cl PCB configuration is most important for optimal recognition by the RyR1 complex and/or critical for sensitizing its activation. Para substitution(s) diminishes the activity with para-chloro having a higher potency than the corresponding para-hydroxy derivative. The addition of a more bulky para-methyl-sulfonyl group eliminates the activity toward RyR1, supporting the importance of the para positions in binding RyR1. The requirement for an intact major T cell immunophilin FKBP12-RyR1 complex was observed with each of 12 active PCB congeners indicating a common mechanism requiring an immunophilin-regulated Ca2+ release channel. An excellent correlation between the relative potencies for doubling [3H]Ry binding and the corresponding initial rates of PCB-induced Ca2+ efflux indicates that [3H]Ry binding analysis provides a measure of dysregulation of microsomal Ca2+ transport. The SAR for activating RyR1 is consistent with those previously reported in several in vivo and in vitro studies, suggesting that a common mechanism may contribute to the toxicity of noncoplanar PCBs. A practical application of the receptor-based screen developed here with RyR1 is that it provides a quantitative SAR that may be useful in predicting biological activity and risk of mixtures containing noncoplanar PCB congeners that have low or a lack of aryl hydrocarbon receptor activity.

Animals↗
PubMed2006

Multiple measures of magnesium status are comparable in mild asthma and control subjects.

Magnesium (Mg) may be a significant factor in asthma management. There is debate about how to best assess Mg status. We evaluated multiple indices of Mg status and lung function in 52 people with mild to moderate asthma and 47 controls. Mg measures included serum total, ionized and erythrocyte Mg, intravenous Mg load retention and dietary recall. Methacholine challenge and pulmonary function tests were used to assess diagnosis and severity of asthma. Mg status was similar in asthma and controls, and was not correlated to lung function. Total serum Mg closely reflected ionized Mg and offers a useful clinical diagnostic monitor.

Adult↗
PubMed2006

Reversal of elevated international normalized ratios and bleeding with low-dose recombinant activated factor VII in patients receiving warfarin.

STUDY OBJECTIVE: To assess the effectiveness of using low-dose recombinant activated factor VII (rFVIIa) to reverse the effects of warfarin in critically ill patients with major bleeding events. DESIGN: Prospective observational study. SETTING: Intensive care unit of a 500-bed university-affiliated hospital. PATIENTS: Sixteen nonhemophiliac patients who had been receiving warfarin and had an acute major bleeding event. INTERVENTION: Patients received rFVIIa 1.2 mg for reversal of anticoagulation. MEASUREMENTS AND MAIN RESULTS: Patients were identified from clinical pharmacology consult service electronic tracking records, and their data were cross-checked with the pharmacy information system. Information collected for each patient included extent of bleeding and magnitude of elevation in international normalized ratio (INR). A mean +/- SD dose of rFVIIa 16.3 +/- 4.1 microg/kg (range 11-25 microg/kg) reduced the mean INR from 2.8 +/- 1.6 (range 1.44-6.34) to 1.07 +/- 0.27 (range 0.86-1.92, p<0.001). A rapid onset of response for achieving a desirable hemostatic effect was observed in 14 of the 16 patients. CONCLUSION: Low-dose rFVIIa appears to be an effective, rapid reversal modality for major bleeding events in the presence of warfarin and an elevated INR. The agent's response is quicker than that expected with fresh frozen plasma combined with vitamin K. In emergency situations, rFVIIa 1.2 mg can be used to reverse the anticoagulant effect of warfarin and other vitamin K antagonists without inducing a hypercoagulable state; the product, however, is expensive.

Adolescent↗
PubMed2005

Tramadol exposures reported to statewide poison control system.

BACKGROUND: Tramadol is a unique analgesic that has been associated with seizures on overdose. OBJECTIVE: To determine the toxic effects associated with tramadol exposure. METHODS: A retrospective chart review of tramadol exposures reported to a multisite, state-wide poison control system over a 2.5-year period was performed. RESULTS: A total of 602 cases were retrieved; 190 had sufficient data for study evaluation. Cases with coingestants or unknown outcomes were eliminated. Of the 190 remaining cases, 55% were females. Acute ingestions represented 90.0%, chronic ingestions 7.9%, and acute on chronic 2.1% of the overdoses. Ages of the patients ranged from 9 months to 80 years. Suicide attempts represented the largest group of exposures. Main symptoms included central nervous system (CNS) depression (27.4%), nausea and vomiting (21.1%), tachycardia (17.4%), and seizures (13.7%). Dosage ranged from a taste amount to 5000 mg. The smallest amount of tramadol associated with seizure was 200 mg, and 84.6% of seizures occurred within 6 hours of time of ingestion. Logistic regression analysis showed an association between seizures and tramadol use in males, chronic use, suicide attempts, intentional abuse or misuse, and tachycardia (HR >100 beats/min). No effect was seen in 36.3% of patients, minor effects in 43.7%, moderate effects in 19.5%, and major effects in 0.5%. Symptoms resolved within 24 hours in 96.7% of the 121 patients who had symptoms. Naloxone improved CNS depression in 7 of 8 patients in whom a response was documented. CONCLUSIONS: Tramadol overdoses frequently cause CNS depression, nausea/vomiting, tachycardia, and seizures. Symptoms generally resolve within 24 hours. Accidental ingestions in children were well tolerated, primarily causing sedation.

Adolescent↗
PubMed2004

Regional variations in the use and awareness of the California Poison Control System.

PURPOSE: To investigate regional variations in public awareness and utilization of the services of Poison Control Centers (PCC) before and after an intervention. METHODS: This study examines call rates of different California regions based on the final five regional PCCs prior to the consolidation of these services under a single statewide California Poison Control System (CPCS) and interventions to increase utilization. Awareness surveys were performed before and after a media campaign that was directed primarily to the Los Angeles basin and to a lesser extent other high Hispanic concentration areas. Focus groups were also utilized to better define specific areas of poison knowledge and awareness of CPCS services. FINDINGS: Large differences in regional California call rates were seen, with the Los Angeles basin showing the lowest utilization of CPCS services compared with the rest of California. Significant seasonal variation in utilization was also found, with the highest average call rates observed in August and the lowest in February. Focus groups demonstrated that urban awareness of PCC was lower than suburban awareness, particularly in monolingual Hispanic households. An improvement was seen after the institution of a media education campaign that included use of Spanish language material and radio spots. Similar increases in call rates were also seen in Fresno county category, with a higher percentage of Hispanic population that was not as aggressively targeted by the awareness campaign. CONCLUSIONS: Significant regional variations in CPCS call rates were found and an increased awareness and utilization was seen in the Los Angeles basin after a directed media campaign compared with most areas of California. Further efforts to increase CPCS utilization in the Los Angeles region, primarily among urban monolingual Hispanics, are needed.

Advertising↗
PubMed2004

Genomic polymorphisms in sepsis.

OBJECTIVE: This article aims to review all relevant genetic polymorphism studies that may contribute to the pathogenesis of sepsis with emphasis on polymorphisms of the innate immunity, pro- and anti-inflammatory cytokines, and coagulation mediators. DATA SOURCE: Published articles reporting on studies of associations between genetic polymorphisms, sepsis, septic shock, and other relevant infectious disease models. DATA ANALYSIS: Research into the pathogenesis of sepsis has led to the development of many potential therapeutic strategies. Several therapeutic agents and treatment modalities have been shown to decrease mortality rates in large, prospective, and randomized clinical trials. However, although these advances have resulted in improved survival for certain patient populations, the overall mortality rate for septic patients remains high. With the rapid development of molecular and genetic techniques, substantial interests have developed in using genomic information to define disease-mediating genetic variants in sepsis. Combined with microarray technology, it is anticipated in the near future that one will be able to tailor drug selection and dosage and predict outcome by correlating genetic profile with disease presentation. Numerous genetic association studies in sepsis have already been reported and more are likely to be published. CONCLUSIONS: Although studies examined in this review are of small heterogeneous populations, the identification of strong associations between certain genetic polymorphisms and increased mortality rate or susceptibility to severe sepsis is intriguing and supports further research using this approach. The establishment of these associations does not equal causation, and further research is required in both genetic and molecular aspect of sepsis.

Humans↗
PubMed2004

Efficacy and safety of the monoclonal anti-tumor necrosis factor antibody F(ab')2 fragment afelimomab in patients with severe sepsis and elevated interleukin-6 levels.

OBJECTIVE: To evaluate whether administration of afelimomab, an anti-tumor necrosis factor F(ab')2 monoclonal antibody fragment, would reduce 28-day all-cause mortality in patients with severe sepsis and elevated serum levels of IL-6. DESIGN: Prospective, randomized, double-blind, placebo-controlled, multiple-center, phase III clinical trial. SETTING: One hundred fifty-seven intensive care units in the United States and Canada. PATIENTS: Subjects were 2,634 patients with severe sepsis secondary to documented infection, of whom 998 had elevated interleukin-6 levels. INTERVENTIONS: Patients were stratified into two groups by means of a rapid qualitative interleukin-6 test kit designed to identify patients with serum interleukin-6 levels above (test positive) or below (test negative) approximately 1000 pg/mL. Of the 2,634 patients, 998 were stratified into the test-positive group, 1,636 into the test-negative group. They were then randomly assigned 1:1 to receive afelimomab 1 mg/kg or placebo for 3 days and were followed for 28 days. The a priori population for efficacy analysis was the group of patients with elevated baseline interleukin-6 levels as defined by a positive rapid interleukin-6 test result. MEASUREMENTS AND MAIN RESULTS: In the group of patients with elevated interleukin-6 levels, the mortality rate was 243 of 510 (47.6%) in the placebo group and 213 of 488 (43.6%) in the afelimomab group. Using a logistic regression analysis, treatment with afelimomab was associated with an adjusted reduction in the risk of death of 5.8% (p = .041) and a corresponding reduction of relative risk of death of 11.9%. Mortality rates for the placebo and afelimomab groups in the interleukin-6 test negative population were 234 of 819 (28.6%) and 208 of 817 (25.5%), respectively. In the overall population of interleukin-6 test positive and negative patients, the placebo and afelimomab mortality rates were 477 of 1,329 (35.9%)and 421 of 1,305 (32.2%), respectively. Afelimomab resulted in a significant reduction in tumor necrosis factor and interleukin-6 levels and a more rapid improvement in organ failure scores compared with placebo. The safety profile of afelimomab was similar to that of placebo. CONCLUSIONS: Afelimomab is safe, biologically active, and well tolerated in patients with severe sepsis, reduces 28-day all-cause mortality, and attenuates the severity of organ dysfunction in patients with elevated interleukin-6 levels.

APACHE↗
PubMed2004

An evaluation of a blind rotational technique for selective mainstem intubation.

OBJECTIVES: Although rare, massive hemoptysis and major bronchial disruptions are associated with high mortality. Selective ventilation of the uninvolved lung can increase the likelihood of survival. Specialized devices used for single lung ventilation are often not readily available and can be difficult to place in the emergency department. The authors evaluated a blind rotational technique for selective mainstem intubation using either a standard endotracheal tube (ET) or a directional-tip endotracheal tube (DTET). METHODS: This was a prospective, randomized trial on 25 human cadavers. The desired side of mainstem intubation was determined by randomization. Each cadaver was used for four ET, four DTET, and four control intubations. In the ET group, the trachea was intubated. The tube was then rotated 90 degrees in the direction of the desired placement and advanced until resistance was met. In the DTET group, the technique was identical, except the trigger was activated to flex the tip during advancement. In the control group, an ET was advanced in neutral alignment until resistance was met. A bronchoscopist blinded to the desired placement determined tube position. Comparison testing was performed using Pearson's chi-square test. RESULTS: When attempting to intubate the left mainstem, use of the ET with the rotational technique was successful 72.3% of the time (95% confidence interval [95% CI] = 57% to 84%). Intubation of the left mainstem using the DTET was successful 68.5% of the time (95% CI = 54% to 81%; p = 0.67). Attempts to selectively intubate the right mainstem using the rotational technique were highly successful in both groups: 94% for the ET (95% CI = 84% to 99%) versus 97.8% for the DTET (95% CI = 89% to 100%). Among controls, the right mainstem was intubated 93% of the time (95% CI = 86% to 97%). CONCLUSIONS: In a cadaveric model, the left mainstem bronchus can be selectively intubated with moderate reliability using this rotational technique. Use of a DTET confers no significant advantage. The ability to generalize these findings to living subjects is unknown.

Cadaver↗
PubMed2004

Epoprostenol in pregnant patients with secondary pulmonary hypertension: two case reports and a review of the literature.

Women who present with pulmonary hypertension during gestation have traditionally been persuaded to terminate their pregnancy. Historically, the mortality associated with this group is very high. Certain patients with a secondary cause of pulmonary hypertension are believed to share similar pathophysiology with primary pulmonary hypertension patients. Recently, new treatments have become available that have slowed disease progression. We present the successful treatment of two patients who presented during late gestation with moderate pulmonary hypertension. Both patients were managed with intravenous vasodilators and anticoagulants without complication. Each patient successfully delivered a healthy child via spontaneous vaginal delivery. The review of the historical management of similar patients including new insights into the etiology of pulmonary arterial hypertension is also included. It highlights the complexity involved in managing such patients and the requirement of a multidisiplinary team approach.

Adult↗
PubMed2003

The presence of a local lung transplant center increases lung procurement rates.

BACKGROUND: The availability of cadaveric organs is the major problem in transplantation today. METHODS: A retrospective review of donors in a single organ procurement organization (OPO) was performed. Donors were divided into three eras: before, during, and after the presence of a local lung transplant program. Lung procurement rates by OPO in the United States in 1999 and 2000 were also retrospectively reviewed. RESULTS: Lung transplant rates were higher in the presence of a local lung program: 4.9% at baseline, 19.1% with a local program, and 7.1% after closure of the local lung program (P<0.01). In the United States, 12.4% of lungs available in OPOs with local lung programs are transplanted, versus 8.9% in OPOs without a local program (P<.001). CONCLUSIONS: Even if donor management protocols are maintained, closure of a local lung program decreases lung recovery rates. This observation supports the importance of maintaining local programs to maximize organ recovery rates.

ABO Blood-Group System↗
PubMed2003

Advances in the management of endobronchial lung malignancies.

The effective palliation of endobronchial malignancies often involves the use of multiple modalities including surgery, external beam radiation, chemotherapy, or a variety of interventional bronchoscopic techniques. The authors discuss in detail recent advances in interventional bronchoscopy that enhance local tumor control. An integrated and individualized approach to the use of these complementary modalities can provide rapid palliation and may improve survival in a subset of patients.

Brachytherapy↗
PubMed2003

Multicenter evaluation of a human monoclonal antibody to Enterobacteriaceae common antigen in patients with Gram-negative sepsis.

OBJECTIVE: To evaluate in Gram-negative sepsis patients the human monoclonal immunoglobulin M antibody (MAB-T88) directed at the enterobacterial common antigen which is a specific surface antigen closely linked to lipopolysaccharide and shared by all members of the Enterobacteriaceae family of Gram-negative bacteria. DESIGN: Prospective, randomized, double-blinded, placebo-controlled, multicenter trial. SETTING: Thirty-three academic medical centers in the United States. PATIENTS: Patients were entered with a clinical diagnosis of sepsis, the presence of either shock or multiple organ dysfunction, and presumptive evidence for Gram-negative infection. INTERVENTIONS: Patients received a single intravenous infusion, over 30 mins, of either 300 mg of MAB-T88 formulated in albumin, or placebo (albumin). MEASUREMENTS AND MAIN RESULTS: The primary analysis group was prospectively identified as those patients with documented evidence of an infection with bacteria of the family Enterobacteriaceae at any site. The primary end point was survival within the first 28 days. A total of 826 patients were enrolled with 55% (n = 455) in the primary analysis group. There were no significant differences between the intervention and control primary analysis group study groups for sites of infection, severity of illness, underlying medical conditions, adequacy of antibiotic or surgical treatment, or other baseline variables except for a higher frequency of chronic renal failure in the MAB-T88 group (4.4% vs. 1.3%, p=.051). The average Acute Physiology and Chronic Health Evaluation II scores were 26.8 +/- 8.6 (mean +/- sd) in the MAB-T88-treated group and 26.5 +/- 8.3 in the placebo-treated group (p =.72). There was no significant difference between MAB-T88- and placebo-treated groups during the first 28-day all-cause mortality in the primary analysis group (34.2% vs. 30.8%, p=.44) or in all 826 patients enrolled (37.0% vs. 34.0%, p=.36). On subset analysis, the use of MAB-T88 was not associated with significant mortality trends. More adverse events were seen with the use of MAB-T88 in the bacteremic enterobacterial common antigen group (p <.05). CONCLUSIONS: Use of the human monoclonal antibody, MAB-T88, did not improve the mortality in patients with presumed Gram-negative sepsis or in those patients with proven enterobacterial common antigen infections. No subset trends were identified that would support further investigation of this agent in sepsis.

Adolescent↗