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1.
Comput Med Imaging Graph ; 38(3): 211-23, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24412393

ABSTRACT

We present a novel real-time method for the 3D reconstruction of the guidewire using a monoplane X-ray. The method consists of two steps: (1) the backprojection step to reconstruct a 3D surface that contains the guidewire and (2) the optimization step to select a curve on the surface that is the best match under the pre-specified constraints. The proposed method utilizes a priori knowledge in the form of a volume that indicates positions of the blood vessels and thus restricts the reconstruction. The reconstruction precision is limited by the local thickness of the vessels. The method is quantitatively evaluated on five phantom datasets and qualitatively on two patient datasets. For the phantom datasets the average reconstruction error is resolution limited to 1-2 voxels and is biased in the depth direction. The worst-case reconstruction error for any point, including the guidewire tip, is not larger than the local vessel thickness. A visual inspection of results for the patient datasets shows the guidewire is always placed in the proper vessel and is aligned with the 2D image, which is sufficient for the guidewire navigation. The developed implementation achieves the processing speed of 12 fps using Core™i7 CPU 920 at 2.67 GHz.


Subject(s)
Algorithms , Angiography/methods , Fiducial Markers , Imaging, Three-Dimensional/methods , Pattern Recognition, Automated/methods , Radiographic Image Interpretation, Computer-Assisted/methods , Radiography, Interventional/methods , Angiography/instrumentation , Computer Systems , Humans , Phantoms, Imaging , Radiographic Image Enhancement/methods , Radiography, Interventional/instrumentation , Reproducibility of Results , Sensitivity and Specificity
2.
Phys Med Biol ; 56(4): 1031-43, 2011 Feb 21.
Article in English | MEDLINE | ID: mdl-21258138

ABSTRACT

Spatial and soft tissue information provided by magnetic resonance imaging can be very valuable during image-guided procedures, where usually only real-time two-dimensional (2D) x-ray images are available. Registration of 2D x-ray images to three-dimensional (3D) magnetic resonance imaging (MRI) data, acquired prior to the procedure, can provide optimal information to guide the procedure. However, registering x-ray images to MRI data is not a trivial task because of their fundamental difference in tissue contrast. This paper presents a technique that generates pseudo-computed tomography (CT) data from multi-spectral MRI acquisitions which is sufficiently similar to real CT data to enable registration of x-ray to MRI with comparable accuracy as registration of x-ray to CT. The method is based on a k-nearest-neighbors (kNN)-regression strategy which labels voxels of MRI data with CT Hounsfield Units. The regression method uses multi-spectral MRI intensities and intensity gradients as features to discriminate between various tissue types. The efficacy of using pseudo-CT data for registration of x-ray to MRI was tested on ex vivo animal data. 2D-3D registration experiments using CT and pseudo-CT data of multiple subjects were performed with a commonly used 2D-3D registration algorithm. On average, the median target registration error for registration of two x-ray images to MRI data was approximately 1 mm larger than for x-ray to CT registration. The authors have shown that pseudo-CT data generated from multi-spectral MRI facilitate registration of MRI to x-ray images. From the experiments it could be concluded that the accuracy achieved was comparable to that of registering x-ray images to CT data.


Subject(s)
Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Animals , Feasibility Studies , Humans
3.
Med Phys ; 37(4): 1884-92, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20443510

ABSTRACT

PURPOSE: The image registration literature comprises many methods for 2D-3D registration for which accuracy has been established in a variety of applications. However, clinical application is limited by a small capture range. Initial offsets outside the capture range of a registration method will not converge to a successful registration. Previously reported capture ranges, defined as the 95% success range, are in the order of 4-11 mm mean target registration error. In this article, a relatively computationally inexpensive and robust estimation method is proposed with the objective to enlarge the capture range. METHODS: The method uses the projection-slice theorem in combination with phase correlation in order to estimate the transform parameters, which provides an initialization of the subsequent registration procedure. RESULTS: The feasibility of the method was evaluated by experiments using digitally reconstructed radiographs generated from in vivo 3D-RX data. With these experiments it was shown that the projection-slice theorem provides successful estimates of the rotational transform parameters for perspective projections and in case of translational offsets. The method was further tested on ex vivo ovine x-ray data. In 95% of the cases, the method yielded successful estimates for initial mean target registration errors up to 19.5 mm. Finally, the method was evaluated as an initialization method for an intensity-based 2D-3D registration method. The uninitialized and initialized registration experiments had success rates of 28.8% and 68.6%, respectively. CONCLUSIONS: The authors have shown that the initialization method based on the projection-slice theorem and phase correlation yields adequate initializations for existing registration methods, thereby substantially enlarging the capture range of these methods.


Subject(s)
Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Algorithms , Animals , Area Under Curve , Dogs , Equipment Design , Fourier Analysis , Humans , Magnetic Resonance Imaging/methods , Models, Statistical , Normal Distribution , Radiography/methods , Reproducibility of Results , X-Rays
4.
Sex Transm Infect ; 82(5): 397-402, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16854997

ABSTRACT

OBJECTIVE: To assess the impact and costs of adding female condoms to a male condom promotion and distribution peer education programme for sex workers in Mombasa, Kenya. DESIGN: A 12 month, prospective study of 210 female sex workers. METHODS: We interviewed participants about their sexual behaviour every 2 months for a total of seven times and introduced female condoms after the third interview. We also collected cost data and calculated the cost and cost effectiveness of adding the female condom component to the existing programme. RESULTS: Introduction of the female condom in an HIV/AIDS prevention project targeting sex workers led to small, but significant, increases in consistent condom use with all sexual partners. However, there was a high degree of substitution of the female condom for male condoms. The cost per additional consistent condom user at a programme level is estimated to be 2160 dollars (1169 pounds sterling, 1711 euros) (95% CI: 1338 to 11 179). CONCLUSIONS: The female condom has some potential for reducing unprotected sex among sex workers. However, given its high cost, and the marginal improvements seen here, governments should limit promotion of the female condom in populations that are already successfully using the male condom. More research is needed to identify effective methods of encouraging sex workers to practise safer sex with their boyfriends.


Subject(s)
Condoms, Female/statistics & numerical data , HIV Infections/prevention & control , Sex Work , Condoms, Female/economics , Condoms, Female/supply & distribution , Cost-Benefit Analysis , Female , HIV Infections/economics , Humans , Kenya , Prospective Studies , Sexual Partners , Unsafe Sex/statistics & numerical data
5.
Sex Transm Infect ; 82(4): 290-4, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16723363

ABSTRACT

OBJECTIVES: To evaluate the effectiveness and cost effectiveness of syndromic sexually transmitted infection (STI) packages on appropriate treatment and preventive management during primary care consultations. METHODS: Cluster randomised trial of 37 Durban primary care clinics randomised to use syndromic packages (containing antibiotics, condoms, partner notification cards, and written information) or not. We assessed outcomes using simulated patients who reported STI symptoms and recorded how they were managed, before and after implementation (269 and 256 simulated patient consultations). We adjusted for baseline values and intra-clinic correlation of outcomes statistically. We used health department information to estimate the extra resources needed to provide the packages to 20 clinics for 1 year and their costs. RESULTS: Simulated patients in intervention clinics were more likely to receive appropriate syndromic STI management (correct treatment plus condoms offered plus partner notification cards offered; prevalence rate ratio 2.3; 95% confidence intervals (CI) 1.6 to 3.0) and to receive more STI advice and information (odds ratio 1.5; 95% CI 1.01 to 2.1). Women were less likely to receive appropriate syndromic STI management. The intervention increased STI information provision in women more than in men. The extra cost per extra patient appropriately managed was $1.51. CONCLUSIONS: Syndromic packages improved syndromic STI management at a reasonable cost and should be used more widely.


Subject(s)
Primary Health Care/economics , Sexually Transmitted Diseases/therapy , Adult , Attitude to Health , Cluster Analysis , Cost-Benefit Analysis , Female , Humans , Length of Stay , Male , Medical History Taking , Patient Simulation , Primary Health Care/standards , Quality of Health Care , Sexually Transmitted Diseases/economics , Syndrome
6.
AIDS Care ; 18(2): 121-7, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16338769

ABSTRACT

The objective of this study is to estimate the medical and non-medical out-of-pocket expenditure on care and support services to PLHA, the financial burden on households, the indirect costs and coping strategies to meet the financial burden. A structured pre-tested questionnaire was used to collect data from a cohort of 153 clients of YRG CARE, a leading Chennai based NGO, who had completed the first and third waves of interview during 2000/01 and 2001/02 respectively. The results show that the median out-of-pocket medical and non-medical expenditures (direct cost) for treatment and services are Rs. 6,000 (US $ 122) in a reference period of six months. Clients on antiretroviral (ARV) drugs spend five times more than those not on ARV. The median direct cost significantly increases with stage of disease, household income, and poverty level. The financial burden of treatment, measured as the ratio of direct cost to household income, is greater on lower income (82%) than on higher income (28%) households. 31% and 45% of the clients reported loss of income and workdays respectively. In conclusion, the direct costs and financial burden of care and support services increase with the stage of disease. The financial burden is disproportionately more on low-income households. HIV/AIDS leads to depletion of savings and increases the indebtedness of households.


Subject(s)
Cost of Illness , HIV Infections/economics , Health Expenditures , Acquired Immunodeficiency Syndrome/drug therapy , Acquired Immunodeficiency Syndrome/economics , Adolescent , Adult , Anti-HIV Agents/economics , Anti-HIV Agents/therapeutic use , Cohort Studies , Drug Therapy, Combination , Female , HIV Infections/drug therapy , Humans , India , Male , Middle Aged , Socioeconomic Factors
7.
Neuroradiology ; 47(10): 735-40, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16001241

ABSTRACT

We present the first clinical results obtained with a novel technique: the three-dimensional [3D] roadmap. The major difference from the standard 2D digital roadmap technique is that the newly developed 3D roadmap is based on a rotational angiography acquisition technique with the two-dimensional [2D] fluoroscopic image as an overlay. Data required for an accurate superimposition of the previously acquired 3D reconstructed image on the interactively made 2D fluoroscopy image, in real time, are stored in the 3D workstation and constitute the calibration dataset. Both datasets are spatially aligned in real time; thus, the 3D image is accurately superimposed on the 2D fluoroscopic image regardless of any change in C-arm position or magnification. The principal advantage of the described roadmap method is that one contrast injection allows the C-arm to be positioned anywhere in the space and allows alterations in the distance between the x-ray tube and the image intensifier as well as changes in image magnification. In the clinical setting, the 3D roadmap facilitated intravascular neuronavigation with concurrent reduction of procedure time and use of contrast medium.


Subject(s)
Cerebral Angiography/methods , Imaging, Three-Dimensional , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/therapy , Radiography, Interventional/methods , Female , Fluoroscopy , Humans , Middle Aged , Tomography, X-Ray Computed
8.
J Pharm Sci ; 90(11): 1859-67, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11745743

ABSTRACT

Membrane-water partitioning of inhibitors of acyl-coenzyme A:cholesterol acyltransferase (ACAT) governs the concentration of inhibitor that ACAT is exposed to and determines the corresponding extent of cholesterol esterification inhibition. Partitioning of the ACAT inhibitors CI-976, CL 277,082, and SaH 58-035 into rat liver microsomes containing ACAT was detected by shifts in the level of inhibition that were independent of inhibitor concentration but inversely dependent on microsome membrane concentration. The equilibrium distribution of the ACAT inhibitors between aqueous and membrane phases was derived directly from these data by application of a previously described method of linear analysis. The accuracy of membrane partitioning analysis based on kinetic data was verified for CI-976 by direct measurements of [14C]CI-976 partitioning into phospholipid membranes. The results show that the ACAT inhibitors are highly partitioned into membranes by factors exceeding 1 x 10(6). This result is consistent with the far greater influence of membrane content over aqueous volume on inhibitor activity. The results demonstrate that the size of the membrane phase in aqueous suspension must be taken into account to obtain accurate and reproducible kinetic characterizations of membrane-active molecules. Analyses of the membrane-dependent shifts in activity can be used to calculate the membrane-water partitioning coefficient of membrane-active molecules such as ACAT inhibitors.


Subject(s)
Enzyme Inhibitors/pharmacokinetics , Membranes, Artificial , Phospholipids/pharmacokinetics , Animals , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Male , Microsomes, Liver/drug effects , Microsomes, Liver/enzymology , Rats , Rats, Sprague-Dawley , Sterol O-Acyltransferase/antagonists & inhibitors , Sterol O-Acyltransferase/metabolism
9.
J Gen Intern Med ; 16(9): 573-82, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11556937

ABSTRACT

OBJECTIVE: To measure the impact of a teaching intervention and to compare process and outcomes of care for HIV-infected patients randomly assigned to a general medicine clinic (GMC) or an infectious disease clinic (IDC) for primary care. DESIGN: Prospective, randomized, controlled trial. SETTING: University hospital in Durham, NC. PATIENTS: Two hundred fourteen consecutive HIV-infected patients presenting for primary care. INTERVENTION: Physicians at the GMC received HIV-related training and evidence-based practice guidelines. MEASUREMENTS: Utilization of services, health-related quality of life, preventive and screening measures, and antiretroviral use for one year. RESULTS: At baseline GMC patients were more likely to be African American (85% vs 71%; P =.03) and had lower baseline CD4+ cell counts than IDC patients (262 +/- 269 vs 329 +/- 275; P =.05). A similar and high proportion of patients in both groups received appropriate preventive care services including Pneumocystis carinii pneumonia (PCP) prophylaxis, pneumococcal vaccination, and antiretroviral therapy. Screening for TB was more frequent in GMC (89% vs 68%; P =.001). In the year following randomization, GMC patients made more visits to the emergency department than IDC patients (1.6 +/- 3.0 vs 0.7 +/- 1.5; P =.05). Hospital use was higher for GMC patients with average length of stay 7.8 +/- 6.3 days compared to 5.7 +/- 3.8 days for IDC patients (P =.01). In analyses, which adjust for potential baseline imbalances, these differences remained. CONCLUSIONS: Targeted education in GMC achieved similar provision of primary care for GMC patients, yet use of health care services was higher for this group. The delivery of adequate primary care is necessary but not sufficient to produce changes in health care utilization.


Subject(s)
Family Practice/education , HIV Infections/therapy , Medicine , Outcome and Process Assessment, Health Care , Outpatient Clinics, Hospital/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Primary Health Care/statistics & numerical data , Specialization , Continuity of Patient Care/organization & administration , Female , HIV Infections/economics , Hospitals, University , Humans , Male , North Carolina , Prospective Studies , Quality of Life , Utilization Review
10.
Am J Gastroenterol ; 94(8): 2033-6, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10445524

ABSTRACT

OBJECTIVES: Although Barrett's esophagus (BE) may be associated with severe gastroesophageal reflux disease (GERD), there are currently no studies that evaluate resource utilization in Barrett's patients. The aims of this study were 1) to determine the cost and number of endoscopies and clinic visits to the GI clinic for GERD or its complications in patients with BE; 2) to determine the pattern and cost of medication use in patients with BE; and 3) to compare medication use by patients with BE to that of patients with insulin-requiring diabetes mellitus (DM). METHODS: Using the cost distribution report data and the pharmacy acquisition costs from the Durham VAMC, we calculated the monthly cost of endoscopies, clinic visits related to GERD, and medication use in 53 patients with BE between 1/1/94 and 1/1/97. We also calculated the average cost of medication use for 55 patients with insulin-requiring DM. RESULTS: All patients with BE were male. Their median age was 64.0 yr (IQR 57-68). Of them, 92% were white; 23% had low-grade dysplasia (LGD). Patients with LGD were more likely to have more than three endoscopies in 3 yr than were those with no LGD (OR 6.3, 95% CI 1.11-35.67). There was no difference in clinic visits in the patients with and without dysplasia (OR 0.335, 95% CI 0.093-1.206). A total of 139 endoscopies and 172 clinic visits were observed. Outpatient care for patients with BE costs approximately $103/month or $1241/yr. Endoscopies and clinic visits accounted for 31.1% and 5.9% of the monthly medical cost, respectively. Medications accounted for 63% of the total cost of care. Prokinetic agents accounted for 0.8% of the total cost of medications, whereas histamine receptor antagonists (H2 blockers) and proton pump inhibitors (PPIs) accounted for 34.6% and 64.6%, respectively. Medication cost per month in patients with BE was approximately $65, similar to that of patients with insulin-requiring DM ($63). CONCLUSIONS: Our conclusions were as follows: 1) Outpatient care for patients with BE costs approximately $1241/yr or ($103/month). 2) Medication use per month accounted for more than half of the total cost; PPIs accounted for 64.6% of total medication cost, suggesting that reflux was severe. 3) Consistent with current surveillance strategies, patients with LGD had more frequent endoscopy than patients with no dysplasia. 4) Medication cost per month in patients with BE is similar to that in patients with DM, another group with a chronic disorder. 5) Those who make health policy can use these results to compare the cost of care of patients with BE to the cost for those with other chronic medical disorders.


Subject(s)
Ambulatory Care/economics , Barrett Esophagus/economics , Managed Care Programs/economics , Aged , Barrett Esophagus/drug therapy , Cohort Studies , Costs and Cost Analysis , Diabetes Mellitus, Type 1/economics , Drug Costs/statistics & numerical data , Esophagoscopy/economics , Female , Gastroesophageal Reflux/drug therapy , Gastroesophageal Reflux/economics , Gastrointestinal Agents/economics , Gastrointestinal Agents/therapeutic use , Humans , Male , Middle Aged , North Carolina , Referral and Consultation/economics
11.
J Nutr ; 129(5): 1010-9, 1999 May.
Article in English | MEDLINE | ID: mdl-10222393

ABSTRACT

The inability to markedly attenuate cholesterol levels in chicken eggs has led to speculation that cholesterol is essential for yolk formation and that egg production would cease when yolk cholesterol deposition was inadequate for embryonic survival. However, this critical level hypothesis remains unproven. Here, we determine the relative responsiveness of laying hens to three select inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), the rate-limiting enzyme of cholesterol biosynthesis. A control diet, either alone or supplemented with one of two dietary levels (0.03 or 0.06%) of atorvastatin, lovastatin, or simvastatin, was fed to White Leghorn hens for 5 wk. Liver cholesterol concentrations (mg/g tissue) were decreased (P 0.05), and 22% (P 0.05), and -3% (P > 0.05)], was much less affected. We concluded that cholesterol per se may not be an obligatory component for yolk formation in chickens and, as such, may be amenable to further pharmacological manipulation


Subject(s)
Chickens/metabolism , Cholesterol/biosynthesis , Egg Yolk/chemistry , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Lipoproteins, VLDL/blood , Liver/drug effects , Animals , Blotting, Northern , Cholesterol/analysis , Female , Gene Expression , Hydroxymethylglutaryl CoA Reductases/genetics , Hydroxymethylglutaryl CoA Reductases/metabolism , Liver/metabolism , Proteins/analysis , RNA, Messenger/metabolism
12.
Epilepsy Res ; 34(2-3): 169-76, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10210032

ABSTRACT

Amygdaloid kindled seizures in the rat induce an abrupt elevation of blood pressure accompanied by a significant decrease in heart rate. The autonomic pharmacology of this response was examined in unanesthetized kindled rats. Muscarinic receptor blockade with atropine (1 mg/kg, intravenous (i.v.)) abolished the seizure-induced bradycardia. The seizure-induced hypertension was unaffected by beta-adrenergic blockade with timolol (1 mg/kg, i.v.), but was reduced by phentolamine (5 mg/kg, subcutaneous (s.c.)), an alpha-adrenergic receptor antagonist. A chemical sympathectomy was induced with 6-hydroxydopamine (100 mg/kg, i.v.), an agent that does not cross the blood-brain barrier. This eliminated the pressor response but did not completely block the seizure-induced bradycardia. The effectiveness of 6-hydroxydopamine was tested with tyramine (0.5 mg/kg, i.v.) an agent that releases endogenous catecholamines. These results indicate amygdaloid kindled seizures activate both branches of the autonomic nervous system. The bradycardia was mediated by the parasympathetic system; the pressor response was caused by an increase in peripheral resistance due to alpha-adrenergic receptor activation. More important, these findings show that kindling is a useful seizure model for future studies on the effect of seizures on cardiovascular function and possible mechanisms of seizure-related sudden unexplained death.


Subject(s)
Autonomic Nervous System/physiopathology , Kindling, Neurologic/physiology , Seizures/etiology , Seizures/physiopathology , Adrenergic alpha-Antagonists/pharmacology , Adrenergic beta-Antagonists/pharmacology , Animals , Atropine/pharmacology , Blood Pressure/drug effects , Heart Rate/drug effects , Male , Muscarinic Antagonists/pharmacology , Oxidopamine/pharmacology , Phentolamine/pharmacology , Rats , Rats, Sprague-Dawley , Sympathectomy, Chemical , Timolol/pharmacology , Tyramine/pharmacology
13.
Med Care ; 37(4 Suppl Va): AS18-26, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10217381

ABSTRACT

BACKGROUND: Department of Veterans Affairs (VA) administrative cost data bases contain inaccuracies and do not provide patient-level data. OBJECTIVE: To describe methods of VA cost determination that are appropriate for specific types of studies and to exemplify these methods with case studies. RESEARCH DESIGN: VA utilization and cost data sources are described, and their limitations highlighted. Strategies for determining costs are discussed for health care that is critical to the study, for other types of health care, and for new programs or interventions. Three case studies are presented to illustrate cost-finding methods. RESULTS: A hybrid approach to determining VA costs is discussed. For health care that is critical to the study, administrative data can be replaced or supplemented with primary data, information from the fiscal or other services, or non-VA data. Primary data are also needed to evaluate new programs or interventions. Less intensive data gathering methods can be used for health care that is not central to the study. The first case study illustrates cost determination for a randomized controlled trial, using an example of alternative ways of maintaining hemodialysis access graft patency. The second case study illustrates the determination of costs for all outpatient procedures to use in billing for veterans with private health insurance. The third case study describes the estimation of cost savings from regionalizing open heart surgery. CONCLUSIONS: Despite problems with VA administrative cost data, accurate VA costs can be determined.


Subject(s)
Costs and Cost Analysis/methods , Health Care Costs , Health Services Research/methods , Hospitals, Veterans/economics , Research Design , United States Department of Veterans Affairs/economics , Decision Support Techniques , Health Services Research/economics , Humans , Insurance, Health , Organizational Case Studies , Renal Dialysis/economics , Thoracic Surgical Procedures/economics , United States
14.
J Chromatogr B Biomed Sci Appl ; 708(1-2): 21-6, 1998 Apr 24.
Article in English | MEDLINE | ID: mdl-9653942

ABSTRACT

Modifications are described for an innovative and widely used high-performance liquid chromatography technique that resolves a very broad spectrum of lipids for quantitation by evaporative light-scattering detection. Substitution of acetone for 2-propanol in a portion of the solvent gradient program yields consistent resolution of diacylglycerol and cholesterol without sacrificing baseline resolution of the remaining major lipid classes. Moreover, previously noted instabilities in triacylglycerol retention time are eliminated. The introduction of acetone also enables a 20% reduction in flow-rate without an increase in total run time. As a further modification of the mobile phase composition, acetic acid and ethanolamine are substituted for the serine-ethylamine combination that was originally shown to improve column performance. The combination of acetic acid and ethanolamine yields the same result but the increased volatility of these solutes over serine results in decreased baseline noise. Finally, 1,2-hexadecanediol is introduced as an internal standard that is well suited for this method. The chromatographic performance obtained with these modifications is demonstrated in compositional analyses of lipid extracts from rat liver, heart, kidney and brain.


Subject(s)
Chromatography, High Pressure Liquid , Lipids/isolation & purification , Animals , Electrochemistry , Light , Lipids/chemistry , Male , Rats , Rats, Sprague-Dawley , Scattering, Radiation
15.
J Lipid Res ; 39(6): 1197-209, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9643351

ABSTRACT

Cholesterol absorption from bile acid micelles is suppressed by phosphatidylcholine (PC) in the micelles. The effects of micellar phospholipid composition on absorption, metabolism, and secretion of lipids were examined in Caco-2 cells incubated with micelles composed of taurocholic acid, cholesterol, oleic acid, monooleoylglycerol, and phospholipid. Significant amounts of all micelle lipids were absorbed from micelles lacking phospholipid. Cholesterol absorption was accompanied by cholesterol esterification and secretion. Micellar oleic acid was also absorbed and reesterified primarily into triacylglycerol which was also secreted. Lipid absorption and secretion from micelles containing lysophosphatidylcholine (LPC) were similar to that obtained with phospholipid-free micelles. LPC was also extensively absorbed. In contrast, incubations with PC-containing micelles resulted in large reductions in the absorption, esterification, and secretion of cholesterol without significant decreases in oleic acid absorption, conversion to acylated lipids, or triacylglycerol secretion. A relatively small reduction in monoacylglycerol absorption from PC-containing micelles was detected. Retinol absorption was not affected by micellar PC. Substitution of LPC for half or more of the PC reversed the PC-dependent decrease in cholesterol absorption. Pancreatic phospholipase A2 (pPLA2) enhanced cholesterol absorption from PC-containing micelles. The pPLA2-dependent increase in cholesterol absorption was inhibited by the pPLA2 inhibitor FPL 67047XX. The results indicate micellized cholesterol absorption by enterocytes is uniquely dependent on the elimination of micellar phosphatidylcholine and thus directly dependent on the lipolytic action of pancreatic phospholipase A2 (pPLA2). Consequently, pPLA2 inhibitors may be a new and novel class of cholesterol absorption inhibitors for therapeutic use.


Subject(s)
Cholesterol/metabolism , Intestinal Absorption/drug effects , Intestinal Mucosa/physiology , Phosphatidylcholines/metabolism , Phosphatidylcholines/pharmacology , Phospholipases A/pharmacology , Vitamin A/pharmacokinetics , Benzhydryl Compounds/pharmacology , Caco-2 Cells , Enzyme Inhibitors/pharmacology , Glycerides , Humans , Intestinal Mucosa/drug effects , Lysophosphatidylcholines/metabolism , Lysophosphatidylcholines/pharmacology , Micelles , Oleic Acid/metabolism , Phospholipases A/antagonists & inhibitors , Phospholipases A2 , Taurocholic Acid , gamma-Aminobutyric Acid/analogs & derivatives , gamma-Aminobutyric Acid/pharmacology
16.
Lipids ; 33(5): 489-98, 1998 May.
Article in English | MEDLINE | ID: mdl-9625596

ABSTRACT

WAY-121,898 is an inhibitor of pancreatic cholesteryl ester hydrolase (pCEH). After confirming its in vitro potency and relative lack of a major effect on acyl-CoA:cholesterol acyltransferase (ACAT), it was found that this compound lowers plasma cholesterol in cholesterol-fed, but not chow-fed, rats. Measures of liver cholesteryl ester content and the direct determination of cholesterol absorption (lymph-fistula model) show that inhibition of cholesterol absorption is at least one mechanism for the observed cholesterol lowering. However, WAY-121,898 was also active when administered parenterally to cholesterol-fed rats, and in cholesterol-fed hamsters cholesterol-lowering occurred with oral dosing despite no change in cholesterol absorption, suggesting other modes of action possibly relating to inhibition of liver CEH. Combination treatment in cholesterol-fed rats with the ACAT inhibitor CI-976 resulted in a greater-than-additive reduction in plasma cholesterol, implying that both pCEH and ACAT may play a role in cholesterol absorption in this species. In rabbits, WAY-121,898 prevented the rise in plasma cholesterol due to the feeding of cholesteryl ester but not in rabbits fed (free) cholesterol. In guinea pigs, the compound induced an increase in adrenal cholesteryl ester mass. Taken together, the overall profile in these animal models suggests that WAY-121,898 inhibits more than just the intestinal (lumenal) pCEH, and that the role of this enzyme in cholesterol metabolism may be different within and across species, the former depending upon the dietary cholesterol load.


Subject(s)
Carbamates/pharmacology , Cholesterol, Dietary , Hypolipidemic Agents/pharmacology , Lipids/blood , Liver/metabolism , Pancreas/enzymology , Sterol Esterase/antagonists & inhibitors , Administration, Oral , Animals , Carbamates/administration & dosage , Cholesterol/blood , Cholesterol Esters/metabolism , Cricetinae , Guinea Pigs , Injections, Subcutaneous , Intestinal Absorption/drug effects , Liver/drug effects , Male , Mesocricetus , Rabbits , Rats , Rats, Sprague-Dawley , Species Specificity , Swine , Triglycerides/blood
17.
Med Care ; 36(3): 271-80, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9520953

ABSTRACT

OBJECTIVES: The authors examined the costs and outcomes resulting from a natural experiment during which direct public access to poison control centers was restricted and then restored. METHODS: Both societal and health care purchaser perspectives were used. Probability data were obtained from a natural experiment during which public callers from a large county in California were electronically blocked from directly accessing the poison control center. Callers were referred to 911, which had direct access to the poison control center, if they thought they had a poisoning emergency. We conducted telephone interviews of: (a) persons who attempted to call the poison control center for a child's poisoning exposure but who did not have direct access (n = 270) and (b) persons who called the poison control center after direct access was restored (n = 279). Cost data were obtained from primary data collection and from other sources. The outcome measure was the appropriateness of the treatment location (at home or at a health care facility). Caller-reported outcomes were also examined. RESULTS: The average additional cost per blocked call was $10.89 from a societal perspective, or $33.14 from a health care purchaser perspective. Fourteen percent of callers with restricted access were treated at an inappropriate location, compared with only 2% of callers with direct poison control center access. Also, 14% did not obtain any professional advice after they attempted to call the poison control center, although 66% of these cases involved potentially toxic substances. Results were robust across a range of sensitivity analyses. CONCLUSION: Restricting direct public access to poison control centers created additional costs to society, the health care sector, and callers.


Subject(s)
Health Services Accessibility/trends , Outcome Assessment, Health Care/statistics & numerical data , Poison Control Centers/statistics & numerical data , California , Decision Support Techniques , Decision Trees , Health Care Costs , Health Care Sector , Health Services Accessibility/economics , Health Services Accessibility/statistics & numerical data , Humans , Outcome Assessment, Health Care/economics , Poison Control Centers/economics , Probability , Sensitivity and Specificity , United States
18.
J Med Chem ; 41(5): 682-90, 1998 Feb 26.
Article in English | MEDLINE | ID: mdl-9513596

ABSTRACT

We prepared a series of alpha-substituted malonester amides that were evaluated for their ability to inhibit acyl-CoA:cholesterol O-acyl transferase activity in vitro and to lower plasma total cholesterol levels in a variety of cholesterol-fed animal models. Compounds of this series were also useful in examining the relationship between adrenal toxicity and ACAT inhibition. One compound from this series, 9f, was a potent inhibitor of ACAT in both the microsomal and cellular assays. It was also bioavailable as determined by both a bioassay and a HPLC-UV assay. This compound was evaluated in both guinea pig and dog models of adrenal toxicity and compared to tetrazole amide 15. In the most sensitive species, the dog, both of these compounds achieved good plasma levels; however, compound 9f caused adrenal necrosis, whereas compound 15 had no effect on the adrenal gland. This adds to the growing body of evidence that the adrenal toxicity observed with ACAT inhibitors may not be mechanism related.


Subject(s)
Adrenal Glands/drug effects , Adrenal Glands/pathology , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/toxicity , Malonates/pharmacology , Malonates/toxicity , Phenylacetates/pharmacology , Phenylacetates/toxicity , Sterol O-Acyltransferase/antagonists & inhibitors , Amides/pharmacology , Amides/toxicity , Animals , Anticholesteremic Agents/chemical synthesis , Biological Availability , Cholesterol/blood , Cholesterol, Dietary/administration & dosage , Chromatography, High Pressure Liquid , Dogs , Enzyme Inhibitors/chemical synthesis , Female , Guinea Pigs , Male , Malonates/chemical synthesis , Mice , Microsomes, Liver/enzymology , Necrosis , Phenylacetates/chemical synthesis , Rats , Rats, Sprague-Dawley , Tetrazoles/pharmacology , Tetrazoles/toxicity
19.
Med Care ; 36(2): 190-201, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9475473

ABSTRACT

OBJECTIVES: This study examines the contribution of the adequacy of nutrition, psychosocial, and health education support service delivery in explaining variation in birth outcomes among Medicaid-eligible women, their provider sites, and practice settings. METHODS: Logistic regression models for low birthweight and preterm birth outcomes are first fitted with medical record data on maternal risks and use of prenatal visits for more than 3,485 women receiving care at 27 ambulatory sites, correcting for clustering of women within sites. RESULTS: The change in variation explained by these models with the addition of the adequacy of support services indicates that providing at least one nutrition, psychosocial, and health education service session each trimester of care contributes significantly to explaining better birth outcomes when compared with providing fewer sessions. When the expected outcome rates calculated with the estimated effects in the models are compared with their observed rates across provider sites and setting types, however, adequacy of service delivery does not help to explain differences in outcomes at individual sites or types of settings. CONCLUSIONS: Although repeated support service sessions during prenatal care improve the chances of avoiding poor birth outcomes in low income women, further adjustments for other differences between women or service delivery are needed to explain variation in outcomes at different sites and practice settings.


Subject(s)
Pregnancy Outcome , Prenatal Care/statistics & numerical data , Social Work/standards , Adult , California/epidemiology , Delivery of Health Care , Female , Humans , Infant, Newborn , Medicaid , Medical Indigency , Medically Uninsured , Pregnancy , Prenatal Care/economics , Prenatal Care/standards , Quality of Health Care , Risk Assessment , Risk Factors , United States
20.
J Health Econ ; 16(3): 343-57, 1997 Jun.
Article in English | MEDLINE | ID: mdl-10169305

ABSTRACT

We used the willingness-to-pay (WTP) method to value the benefits of poison control centers when direct access was blocked, comparing WTP among: (1) blocked callers (n = 396), (2) callers after access was restored (n = 418), and (3) the general population (n = 119). Mean monthly WTP was $6.70 (blocked callers), $6.11 (non-blocked callers), and $2.55 (general population). Blocked and non-blocked callers had a significantly higher WTP than general population respondents (p < 0.001). We conclude that the WTP method measured benefits that are difficult to quantify; however, WTP surveys need to be carefully conducted to minimize bias. We discuss how this approach could be useful for other health care services.


Subject(s)
Hotlines/economics , Poison Control Centers/economics , Cost-Benefit Analysis , Health Care Surveys/methods , Health Services Accessibility , Models, Econometric , Poison Control Centers/statistics & numerical data , Regression Analysis , San Francisco , Taxes , United States
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