PubMed Health⌕ Search

Biomedical subjects

L Goldman

Publications and source records attributed to L Goldman.

At least 19 recordsLinked to original sources
PubMed2006

Quantitative analysis of a fully generalized four-state kinetic scheme.

To describe the macroscopic behavior of many ion channels, at a minimum a four-state kinetic scheme is needed to provide for three processes: a delay in activation development, the activation process, and inactivation. I present here an analytical solution for a fully generalized four-state kinetic scheme in which every state can transit to every other state and any initial conditions can be specified. The solution describes the time courses of the probabilities of occupancy of each state during a step change in the rate constants of the scheme and includes closed-form expressions for the relaxation time constants and steady-state probabilities of occupancy as functions of the rate constants. Solutions for several relevant special cases are also included along with demonstrations that the general solution yields the correct behavior for several reduced or special cases where the result is independently known.

Cell Membrane↗
PubMed2005

Overestimation of clinical diagnostic performance caused by low necropsy rates.

BACKGROUND: Diagnostic sensitivity is calculated as the number of correct diagnoses divided by the sum of correct diagnoses plus the number of missed or false negative diagnoses. Because missed diagnoses are generally detected during clinical follow up or at necropsy, the low necropsy rates seen in current practice may result in overestimates of diagnostic performance. Using three target conditions (aortic dissection, pulmonary embolism, and active tuberculosis), the prevalence of clinically missed cases among necropsied and non-necropsied deaths was estimated and the impact of low necropsy rates on the apparent sensitivity of antemortem diagnosis determined. METHODS: After reviewing case series for each target condition, the most recent study that included cases first detected at necropsy was selected and the reported sensitivity of clinical diagnosis adjusted by estimating the total number of cases that would have been detected had all decedents undergone necropsy. These estimates were based on available data for necropsy rates, time period, country (US v non-US), and case mix. RESULTS: For all three target diagnoses, adjusting for the estimated prevalence of clinically missed cases among non-necropsied deaths produced sensitivity values outside the 95% confidence interval for the originally reported values, and well below sensitivities reported for the diagnostic tests that are usually used to detect these conditions. For active tuberculosis the sensitivity of antemortem diagnosis decreased from an apparent value of 96% to a corrected value of 83%, with a plausible range of 42-91%; for aortic dissection the sensitivity decreased from 86% to 74%; and for pulmonary embolism the reduction fell only modestly from 97% to 91% but was still lower than generally reported values of 98% or more. CONCLUSIONS: Failure to adjust for the prevalence of missed cases among non-necropsied deaths may substantially overstate the performance of diagnostic tests and antemortem diagnosis in general, especially for conditions with high early case fatality.

Aortic Dissection↗
PubMed2003

An antisense oligonucleotide against H1 inhibits the classical sodium current but not ICa(TTX) in rat ventricular cells.

ICa(TTX) is a sodium current component, functionally distinct from the main body of sodium current, seen in cardiac and other cells. To determine if ICa(TTX) channels are a separate isoform from the classical cardiac sodium channels, we exposed rat ventricular cells in primary culture to an antisense oligonucleotide (AON) directed against rH1 (rNav1.5): 5'-CTCCTCATACCCTCT-3'. The homologous human sequence has been identified (and confirmed by us on HEK 293 cells) as effective against hH1 expressed heterologously. Scrambled sequence (5'-CCCCCCTTATCTACT-3') controls were also included. The AON (10 microM; day 2 of exposure) reduced the classical sodium current by 69.6 % compared to untreated and 60.8 % compared to scrambled sequence (10 microM; day 2 of exposure) controls (mean +/- S.E.M. maximum peak inward current density of -8.23 +/- 0.60 pA pF-1, 18 cells, for untreated; -6.37 +/- 0.79 pA pF-1, 16 cells, for scrambled sequence; and -2.50 +/- 0.31 pA pF-1, 18 cells, for AON-treated cells). The two control groups are not significantly different from each other, but are both significantly different from the AON-treated group (P < 0.001). The inhibition was specific for sodium channels, with no significant AON effect on the L-type calcium current. This confirms that H1 generates the classical cardiac sodium current. This same AON at the same concentration and time of exposure had no significant effect on ICa(TTX) (mean of -4.72 +/- 0.55, 15 cells; -5.47 +/- 0.53, 13 cells; and -5.04 +/- 0.63 pA pF-1, 15 cells, for untreated controls, scrambled controls and AON treated, respectively). Hence, ICa(TTX), which is functionally distinct from the classical cardiac sodium current, is encoded by a distinct gene.

Animals↗
PubMed2001

Passing the clinical baton: 6 principles to guide the hospitalist.

Hospitalist systems make it increasingly common for responsibility for a patient to be passed from one physician to another. During such transfers, patients' outcomes and satisfaction can benefit from better communication between hospitalists and the primary care physicians whose patients they care for. We propose 6 principles to guide such communication, to ensure that critical information about patients is not lost and to optimize the quality of care. We also discuss special considerations for patients discharged to a skilled nursing facility or to home with home care.

Attitude of Health Personnel↗
PubMed2001

Right heart catheterization and cardiac complications in patients undergoing noncardiac surgery: an observational study.

CONTEXT: Right heart catheterization (RHC) is commonly performed before high-risk noncardiac surgery, but the benefit of this strategy remains unproven. OBJECTIVE: To evaluate the relationship between use of perioperative RHC and postoperative cardiac complication rates in patients undergoing major noncardiac surgery. DESIGN: Prospective, observational cohort study. SETTING: Tertiary care teaching hospital in the United States. PATIENTS: Patients (n = 4059 aged >/=50 years) who underwent major elective noncardiac procedures with an expected length of stay of 2 or more days between July 18, 1989, and February 28, 1994. Two hundred twenty one patients had RHC and 3838 did not. MAIN OUTCOME MEASURE: Combined end point of major postoperative cardiac events, including myocardial infarction, unstable angina, cardiogenic pulmonary edema, ventricular fibrillation, documented ventricular tachycardia or primary cardiac arrest, and sustained complete heart block, classified by a reviewer blinded to preoperative data. RESULTS: Major cardiac events occurred in 171 patients (4.2%). Patients who underwent perioperative RHC had a 3-fold increase in incidence of major postoperative cardiac events (34 [15.4%] vs 137 [3.6%]; P<.001). In multivariate analyses, the adjusted odds ratios (ORs) for postoperative major cardiac and noncardiac events in patients undergoing RHC were 2.0 (95% confidence interval [CI], 1.3-3.2) and 2.1 (95% CI, 1.2-3.5), respectively. In a case-control analysis of a subset of 215 matched pairs of patients who did and did not undergo RHC, adjusted for propensity of RHC and type of procedure, patients who underwent perioperative RHC also had increased risk of postoperative congestive heart failure (OR, 2.9; 95% CI, 1.4-6.2) and major noncardiac events (OR, 2.2; 95% CI, 1.4-4.9). CONCLUSIONS: No evidence was found of reduction in complication rates associated with use of perioperative RHC in this population. Because of the morbidity and the high costs associated with RHC, the impact of this intervention in perioperative care should be evaluated in randomized trials.

Aged↗
PubMed2001

Impact of age on perioperative complications and length of stay in patients undergoing noncardiac surgery.

BACKGROUND: Major surgical procedures are performed with increasing frequency in elderly persons, but the impact of age on resource use and outcomes is uncertain. OBJECTIVE: To evaluate the influence of age on perioperative cardiac and noncardiac complications and length of stay in patients undergoing noncardiac surgery. DESIGN: Prospective cohort study. SETTING: Urban academic medical center. PATIENTS: Consecutive sample of 4315 patients 50 years of age or older who underwent nonemergent major noncardiac procedures. MEASUREMENTS: Major perioperative complications (cardiac and noncardiac), in-hospital mortality, and length of stay. RESULTS: Major perioperative complications occurred in 4.3% (44 of 1015) of patients 59 years of age or younger, 5.7% (93 of 1646) of patients 60 to 69 years of age, 9.6% (129 of 1341) of patients 70 to 79 years of age, and 12.5% (39 of 313) of patients 80 years of age or older (P < 0.001). In-hospital mortality was significantly higher in patients 80 years of age or older than in those younger than 80 years of age (0.7% vs. 2.6%, respectively). Multivariate analyses indicated an increased odds ratio for perioperative complications or in-hospital mortality in patients 70 to 79 years of age (1.8 [95% CI, 1.2 to 2.7]) and those 80 years of age or older (OR, 2.1 [CI, 1.2 to 3.6]) compared with patients 50 to 59 years of age. Patients 80 years of age or older stayed an average of 1 day more in the hospital, after adjustment for other clinical data (P = 0.001). CONCLUSIONS: Elderly patients had a higher rate of major perioperative complications and mortality after noncardiac surgery and a longer length of stay, but even in patients 80 years of age or older, mortality was low.

Age Factors↗
PubMed2001

Usefulness of transthoracic echocardiography as a tool for risk stratification of patients undergoing major noncardiac surgery.

Transthoracic echocardiography (TTE) is frequently ordered before noncardiac surgery, although its ability to predict perioperative cardiac complications is uncertain. To evaluate the incremental information provided by TTE after consideration of clinical data for prediction of cardiac complications after noncardiac surgery, 570 patients who underwent TTE before major noncardiac surgery at a university hospital were studied. Preoperative clinical data and clinical outcomes were collected prospectively according to a structured protocol. TTE data included left ventricular (LV) function, hypertrophy indexes, and Doppler-derived measurements. In univariate analyses, preoperative systolic dysfunction was associated with postoperative myocardial infarction (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.1 to 7.0), cardiogenic pulmonary edema (OR 3.2, 95% CI 1.4 to 7.0), and major cardiac complications (OR 2.4, 95% Cl 1.3 to 4.5). Moderate to severe LV hypertrophy, moderate to severe mitral regurgitation, and increased aortic valve gradient were also associated with major cardiac events (OR 2.3, 95% CI 1.2 to 4.6; OR 2.2, 95% CI 1.1 to 4.3; OR 2.1, 95% CI 1.0 to 4.5, respectively). In logistic regression analysis, models with echocardiographic variables predicted major cardiac complications significantly better than those that included only clinical variables (c statistic 0.73 vs 0.68; p <0.05). Echocardiographic data added significant information for patients at increased risk for cardiac complications by clinical criteria, but not in otherwise low-risk patients. In conclusion, preoperative TTE before noncardiac surgery can provide independent information about the risk of postoperative cardiac complications in selected patients.

Aged↗
PubMed2001

I(Ca(TTX)) channels are distinct from those generating the classical cardiac Na(+) current.

The Na(+) current component I(Ca(TTX)) is functionally distinct from the main body of Na(+) current, I(Na). It was proposed that I(Ca(TTX)) channels are I(Na) channels that were altered by bathing media containing Ca(2+), but no, or very little, Na(+). It is known that Na(+)-free conditions are not required to demonstrate I(Ca(TTX).) We show here that Ca(2+) is also not required. Whole-cell, tetrodotoxin-blockable currents from fresh adult rat ventricular cells in 65 mm Cs(+) and no Ca(2+) were compared to those in 3 mM Ca(2+) and no Cs(+) (i.e., I(Ca(TTX))). I(Ca(TTX)) parameters were shifted to more positive voltages than those for Cs(+). The Cs(+) conductance-voltage curve slope factor (mean, -4.68 mV; range, -3.63 to -5.72 mV, eight cells) is indistinguishable from that reported for I(Ca(TTX)) (mean, -4.49 mV; range, -3.95 to -5.49 mV). Cs(+) current and I(Ca(TTX)) time courses were superimposable after accounting for the voltage shift. Inactivation time constants as functions of potential for the Cs(+) current and I(Ca(TTX)) also superimposed after voltage shifting, as did the inactivation curves. Neither of the proposed conditions for conversion of I(Na) into I(Ca(TTX)) channels is required to demonstrate I(Ca(TTX)). Moreover, we find that cardiac Na(+) (H1) channels expressed heterologously in HEK 293 cells are not converted to I(Ca(TTX)) channels by Na(+)-free, Ca(2+)-containing bathing media. The gating properties of the Na(+) current through H1 and those of Ca(2+) current through H1 are identical. All observations are consistent with two non-interconvertable Na(+) channel populations: a larger that expresses little Ca(2+) permeability and a smaller that is appreciably Ca(2+)-permeable.

Animals↗
PubMed2001

The effect of risk factor reductions between 1981 and 1990 on coronary heart disease incidence, prevalence, mortality and cost.

OBJECTIVES: We sought to estimate the impact and cost-effectiveness of risk factor reductions between 1981 and 1990. BACKGROUND: Coronary heart disease (CHD) mortality rates have declined dramatically, partly as a result of reductions in CHD risk factors. METHODS: We used the CHD Policy Model, a validated computer-simulation model, to estimate the effects of actual investments made to change coronary risk factors between 1981 and 1990, as well as the impact of these changes on the incidence, prevalence, mortality and costs of CHD during this period and projected to 2015. RESULTS: Observed changes in risk factors between 1981 and 1990 resulted in a reduction of CHD deaths by approximately 430,000 and overall deaths by approximately 740,000, with an estimated cost-effectiveness of about $44,000 per year of life saved during this period, based on the estimated actual costs of the interventions used. However, because much of the benefit of risk factor reductions is delayed, the estimated reductions for the 35-year period of 1981 to 2015 were 3.6 million CHD deaths and 1.2 million non-CHD deaths, at a cost of only about $5,400 per year of life saved. CONCLUSIONS: Aggregate efforts to reduce risk factors between 1981 and 1990 have led to substantial reductions in CHD and should be well worth the cost, largely because of population-wide changes in life-style and habits. Some interventions are much better investments than others, and attention to such issues could lead to better use of resources and better outcomes in the future.

Adult↗
PubMed2001

Cost-effectiveness of pravastatin therapy for survivors of myocardial infarction with average cholesterol levels.

BACKGROUND: The objective of this study was to assess the cost-effectiveness of pravastatin therapy in survivors of myocardial infarction with average cholesterol levels. METHODS: We performed a cost-effectiveness analysis based on actual clinical, cost, and health-related quality-of-life data from the Cholesterol and Recurrent Events (CARE) trial. Survival and recurrent coronary heart disease events were modeled from trial data in Markov models, with the use of different assumptions regarding the long-term benefit of therapy. RESULTS: Pravastatin therapy increased quality-adjusted life expectancy at an incremental cost of $16,000 to $32,000 per quality-adjusted life-year gained. In subgroup analyses, the cost-effectiveness of pravastatin therapy was more favorable for patients >60 years of age and for patients with pretreatment low-density lipoprotein cholesterol levels >125 mg/dL. Results were sensitive to the cost of pravastatin and to assumptions about long-term survival benefits from pravastatin therapy. CONCLUSIONS: The cost-effectiveness of pravastatin therapy in survivors of myocardial infarction with average cholesterol levels compares favorably with other interventions.

Anticholesteremic Agents↗