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Biomedical subjects

B Alexander

Publications and source records attributed to B Alexander.

At least 73 records · Page 4Linked to original sources

TIMI frame count: a quantitative method of assessing coronary artery flow.

BACKGROUND: Although the Thrombolysis in Myocardial Infarction (TIMI) flow grade is valuable and widely used qualitative measure in angiographic trials, it is limited by its subjective and categorical nature. METHODS AND RESULTS: In normal patients and patients with acute myocardial infarction (MI) (TIMI 4), the number of cineframes needed for dye to reach standardized distal landmarks was counted to objectively assess an index of coronary blood flow as a continuous variable. The TIMI frame-counting method was reproducible (mean absolute difference between two injections, 4.7 +/- 3.9 frames, n=85). In 78 consecutive normal arteries, the left anterior descending coronary artery (LAD) TIMI frame count (36.2 +/- 2.6 frames) was 1.7 times longer than the mean of the right coronary artery (20.4 +/- 3.0) and circumflex counts (22.2 +/- 4.1, P < .001 for either versus LAD). Therefore, the longer LAD frame counts were corrected by dividing by 1.7 to derive the corrected TIMI frame count (CTFC). The mean CTFC in culprit arteries 90 minutes after thrombolytic administration followed a continuous unimodal distribution (there were not subpopulations of slow and fast flow) with a mean value of 39.2 +/- 20.0 frames, which improved to 31.7 +/- 12.9 frames by 18 to 36 hours (P < .001). No correlation existed between improvements in CTFCs and changes in minimum lumen diameter (r=-.05, P=.59). The mean 90-minute CTFC among nonculprit arteries (25.5 +/- 9.8) was significantly higher (flow was slower) compared with arteries with normal flow in the absence of acute MI (21.0 +/- 3.1, P < .001) but improved to that of normal arteries by 1 day after thrombolysis (21.7 +/- 7.1, P=NS). CONCLUSIONS: The CTFC is a simple, reproducible, objective and quantitative index of coronary flow that allows standardization of TIMI flow grades and facilitates comparisons of angiographic end points between trials. Disordered resistance vessel function may account in part for reductions in flow in the early hours after thrombolysis.

Blood Flow Velocity↗

Gamma delta T lymphocyte regeneration after T lymphocyte-depleted bone marrow transplantation from mismatched family members or matched unrelated donors.

The recovery of gamma delta T lymphocytes was studied in 31 recipients of T cell-depleted allogeneic bone marrow (BMT) to determine if the dynamics of reconstitution could be related to graft-versus-host disease (GVHD) or other complications of marrow transplantation. Two distinct patterns of regeneration were apparent. In 12 patients, there was a progressive rise in both the percentage and the absolute number of peripheral blood gamma delta T cells over the first year post-transplantation, but these increases never breached levels found in 14 healthy donors. Each of the 19 remaining patients had abnormally high proportions and numbers of gamma delta T cells on at least two occasions following transplantation. The clinical factor that best explained these observations was the frequency of intercurrent infections. Of 19 patients with abnormally increased percentages and numbers of gamma delta T lymphocytes, 18 had one or more episodes of confirmed viral or fungal infection, contrasted with only two of 12 in the comparison group (P < 0.001). There was no significant association of gamma delta T cell recovery patterns with the presence of GVHD (P = 0.33). We conclude that the recovery of gamma delta T lymphocytes after marrow transplantation may vary. Supranormal levels of this T cell subset are associated with infection and may contribute significantly to cellular immune defenses against fungal or viral disease.

Adolescent↗

Transformation of astrocytes in transgenic mice expressing SV40 T antigen under the transcriptional control of the glial fibrillary acidic protein promoter.

There are many animal models of glioma, but few that represent the biology of low-grade tumors and allow the study of the genetic mechanisms of glial oncogenesis. We report the in vivo transformation of astrocytic cells in transgenic mice by the SV40 T antigen under the control of the 5'-flanking sequence of the murine glial fibrillary acidic protein (GFAP) gene. High levels of T antigen expression were detectable in a tissue distribution that mirrored the normal expression of GFAP. This was associated with a consistent phenotype in the founder mice. Diffuse proliferation occurred in cells of the periventricular subependymal zone with diffuse invasion into the brain parenchyma, leading to death by 19-30 days postnatally. Transformed cells exhibited secondary structuring, a typical histopathological feature of human astrocytomas. Early passage cultures of these cells expressed GFAP in vitro and were transformed on the basis of tumor formation after transplantation into nude mice. These results demonstrate the susceptibility of periventricular astrocytic cells in the immature brain to malignant transformation. Furthermore, this study demonstrates the potential of the transgenic approach for the in vivo determination of genetic events involved in astrocyte transformation and for the development of novel models of astrocytoma.

Animals↗

Angiographic predictors of reocclusion after thrombolysis: results from the Thrombolysis in Myocardial Infarction (TIMI) 4 trial.

OBJECTIVES: This study attempted to determine which lesion characteristics are associated with reocclusion by 18 to 36 h. BACKGROUND: Reocclusion of the infarct-related artery after successful reperfusion is associated with significant morbidity and up to a threefold increase in mortality. METHODS: Two hundred seventy-eight patients with acute myocardial infarction were randomized to receive either anisoylated plasminogen streptokinase activator complex (APSAC) or recombinant tissue-type plasminogen activator (rt-PA) or their combination. Culprit arteries were assessed for Thrombolysis in Myocardial Infarction (TIMI) flow grade, lesion ulceration, thrombus, collateral circulation and eccentricity. Minimal lumen diameter, percent diameter stenosis and lesion irregularity (power) were calculated using quantitative angiography. RESULTS: Reocclusion was observed more frequently in arteries with TIMI 2 versus TIMI 3 flow (10.4% vs. 2.2%, p = 0.003), in ulcerated lesions (10.7% vs. 3.0%, p = 0.009) and in the presence of collateral vessels (18.2% vs. 5.6%, p = 0.03). Similar trends were observed for eccentric (7.3% vs. 2.3%, p = 0.06) and thrombotic (8.4% vs. 3.3%, p = 0.06) lesions. Reocclusion was associated with more severe mean percent stenosis (77.9% vs. 73.9%, p = 0.04). Lesion length, reference segment diameter and Fourier measures of lesion irregularity were not associated with reocclusion. CONCLUSIONS: Several simply assessed angiographic variables, such as the presence of TIMI grade 2 flow, ulceration, collateral vessels and greater percent diameter stenosis at 90 min after thrombolytic therapy, are associated with significantly higher rates of infarct-related artery reocclusion by 18 to 36 h and may aid in identifying the subset of patients who are at significantly higher risk of early reocclusion and who potentially warrant further early pharmacologic or mechanical intervention.

Adult↗

The cost of comprehensive preventive medical services for adolescents.

OBJECTIVES: To address the need for clinical preventive services for 11- to 21-year-old males and females and provide cost estimates for those services under a fee-for-service system. Preventive services include screening, health promotion, and immunizations. DESIGN: The prevalence of adolescent morbidities was derived from national surveys. Estimated costs of these morbidities were obtained from published data and adjusted for 1992 dollars using the Consumer Price Index. The estimated costs of preventive services for adolescents under a fee-for-service system were derived from a 1993 survey of nine Blue Cross and Blue Shield plans and four insurance companies. MAIN OUTCOME MEASURES: The cost of adolescent morbidities includes only direct medical costs for a single year and excludes long-term and indirect costs. The cost of clinical preventive services is calculated at 100% participation levels. RESULTS: Each year, an estimated $33.5 billion is spent on medical treatment for select adolescent morbidities, approximately $859 per adolescent per year; this is a conservative estimate. The average cost of clinical preventive services per adolescent per year would be approximately $130 in a fee-for-service system, although these are not entirely "new" costs because payers already incur screening costs for some conditions. CONCLUSION: The cost-effectiveness of clinical interventions for various health risk behaviors among adolescents is unknown. It appears that preventive interventions would have to eliminate 15% of adolescent morbidities overall to break even in economic terms.

Accidents, Traffic↗

Hepatic function during prolonged isolated rat liver perfusion using a new miniaturized perfusion circuit.

Previous designs of isolated rat liver perfusion circuits used for toxicological investigations are often expensive, cumbersome, or traumatic in relation to hepatic biocompatibility following extended perfusion times. A new, miniaturized circuit that incorporates a novel design of organ bath, to maintain a buoyant preparation, and a high-efficiency miniaturized membrane tubing oxygenator is described. Livers from male Sprague-Dawley rats were perfused continuously for 6 hr in vitro using rat blood diluted to a perfusate hematocrit of 9.75 +/- 0.35% with Krebs-Henseleit buffer (KHB). Hepatic function was evaluated by measurement of perfusion pressure, flow rate, bile volume production, bile bilirubin content, hepatic oxygen uptake (HOU), bromosulphthalein (BSP) removal, hepatic enzyme activities, and electrolyte concentrations, and finally by histological examination. Perfusion pressure and flow rate remained stable at 8.7 +/- 1.7 mmHg and 1.92 +/- 0.06 mL min-1 g-1 liver, respectively. Bile volume production and HOU were maximal at 784 +/- 84 microL h-1 and 0.99 micromol/L min-1 g-1 respectively. Erythrocyte damage in the perfusate was evaluated by measurement of reduction in perfusate hematocrit from 9.75 +/- 0.35% to 9.27 +/- 0.24%, and increases in plasma free hemoglobin, which rose from 85.8 +/- 12.3 mg% to 650.1 +/- 53.3 mg% over the 6-hr perfusion period studied. Using bile volume production, hepatic oxygen uptake, and the liberation of plasma free hemoglobin as the most sensitive indices of adverse conditions, the new circuit was capable of supporting an isolated perfused rat liver for periods of up to 6 hr under close-to-physiological conditions.

Animals↗

Phlebotomine sandflies associated with a focus of cutaneous leishmaniasis in Valle del Cauca, Colombia.

A survey was made of the phlebotomine sandfly fauna of La Guaira, a village with coffee plantations near Cali, Colombia, from which cases of American cutaneous leishmaniasis had been reported due to Leishmania (Viannia) panamensis and Le. (V.) braziliensis. Among six species of sandfly collected on human bait, Lutzomyia youngi was most important in terms of biting nuisance. Lu.columbiana, Lu.lichyi and Lu.scorzai as well as Lu.youngi adults occurred throughout the year. Sandfly man-biting activity occurred throughout the night and was highest within 2 h of sunset. Despite its abundance in nocturnal samples, Lu.youngi was rarely taken in diurnal resting site collections. In contrast, Lu.lichyi was collected on tree-trunks during the day in large numbers and was the only species biting in daylight. The implications of these and other findings for leishmaniasis control measures in La Guaira are considered.

Animals↗

Evaluation of deltamethrin-impregnated bednets and curtains against phlebotomine sandflies in Valle del Cauca, Colombia.

The effectiveness of bednets and curtains (nylon mesh 64 per cm2) impregnated with deltamethrin at 26 mg a.i./m2 in reducing the biting nuisance caused by three phlebotomine sandfly species: Lutzomyia columbiana, Lu.lichyi and the predominant Lu.youngi (Diptera: Psychodidae), was evaluated at La Guaira, a rural settlement in Valle de Cauca near Cali, Colombia. Pairs of volunteers collected sandflies under impregnated bednets, in rooms protected by impregnated curtains or in unprotected rooms in a randomized matched design. Collections were made in three houses per night on three consecutive nights, so that each house was sampled under each of the three treatments. This routine was repeated at 2-week intervals for 6 months. There was no significant difference between the overall numbers of sandflies collected in rooms with or without impregnated curtains. Only 0.14 sandflies/man-hour were caught on human bait under impregnated bednets, significantly fewer than the numbers collected on human bait outside the nets in the same room (1.91) or in unprotected rooms (3.29). In a second set of experiments carried out in La Guaira and the neighbouring community of Jiguales, the effect of deltamethrin impregnation was evaluated by comparing numbers of sandflies collected on human bait under treated and untreated nets. Significantly fewer were collected under the impregnated nets (0.25 v. 0.69/man-hour). Wild-caught female Lu.youngi exposed to treated netting for 2 min in the laboratory all died with 24 h. The impact of deltamethrin-impregnated bednets was considered to be useful against Lu.youngi and other potential vectors of leishmaniasis in such communities.

Animals↗

The transhepatic response to noradrenaline in the rabbit liver: the influence of arterioportal pressure gradient.

The dose-related responses of the hepatic arterial and portal venous vascular beds to bolus administration of noradrenaline (10(-10)-10(-4) mol), injected into the hepatic artery and portal vein, were studied in the isolated dual-perfused rabbit liver at both basal and raised tone. The transhepatic ratio, defined as the ratio between the intra-arterial molar ED50 dose and the intraportal dose required to give the same arterial response, was calculated for arterial and venous responses to noradrenaline. At basal tone, the transhepatic ratio for hepatic arterial vasoconstrictive responses was 500. Portal venous vasoconstrictive responses were similar in potency independent of injection site but differed significantly in analysis of dose-response slope and maximal response. At raised tone, the arterio-portal pressure gradient increased by 68.5 mmHg and there was a 10-fold increase in the transhepatic ratio for hepatic arterial responses, while the portal venous responses remained unchanged. These results demonstrate that arterio-portal pressure gradient has a powerful effect on transhepatic action of noradrenaline, and suggest a pre-sinusoidal site for the generation of both hepatic arterial and portal venous vascular resistance.

Animals↗

Laboratory and field evaluations of a repellent soap containing diethyl toluamide (DEET) and permethrin against phlebotomine sand flies (Diptera: Psychodidae) in Valle del Cauca, Colombia.

The repellency and insecticidal efficacy of Nopikex, a soap formulation containing 20% diethyl toluamide and 0.5% permethrin, was evaluated against a laboratory colony of phlebotomine sand flies (Lutzomyia longipalpis). The repellency of Nopikex soap was also compared with that of a placebo soap against another species (Lu. youngi) in a forest near Tulua, Valle del Cauca, Colombia. In laboratory trials of the soap, no reduction in repellency was seen 4 hr after application, but within 8 hr, repellency decreased significantly to 67.0% of the initial value (P < 0.05) based on calculations of the coefficient of protection (CP). Under field conditions, the soap gave up to 100% protection immediately after application, but within 4 hours its CP value had decreased to a median value of only 44.3%. The placebo soap was also found to be somewhat repellent when compared with no treatment, giving a median CP value of 67.7 immediately after application. No significant mortality was seen in sand flies within 24 hr of exposure to the soap in the laboratory, even in those that had fed on protected volunteers.

Animals↗

A review of bartonellosis in Ecuador and Colombia.

A review of the literature regarding bartonellosis or Carrion's disease in Colombia and Ecuador is presented, together with observations made by the author in areas of both countries from which the disease has been recorded. There is evidence from pre-Columbian artifacts that verruga peruana, the cutaneous form of the disease, was present in Ecuador at least 1,000 years prior to the arrival of Europeans. These artifacts were discovered in the coastal province of Manabi, a low-lying area very different from the high Andean valleys of Peru with which bartonellosis is normally associated. Most of the cases recorded in recent years from this coastal area. The disease does not appear to have occurred in Colombia before the 1930s and only one case has been reported during the past 40 years. The possibility of many more subclinical cases being present in both Ecuador and Colombia is discussed, together with the possibility that the acquired immunodeficiency syndrome epidemic will reveal a higher prevalence among the inhabitants of endemic areas than previously suspected. Although the suspected vector of Bartonella bacilliformis, the sand fly Lutzomyia verrucarum, has not been recorded from Ecuador or Colombia, related species are present in endemic areas and may be involved in transmission.

Bartonella Infections↗

An evaluation of whether duration of perfusion alters vascular responses in the isolated dual-perfused rabbit liver.

The isolated dual-perfused rabbit liver has been used to characterize hepatic arterial vascular receptors. These hepatic arterial responses are reproducible for 2.5 hr. Further studies in relation to the assessment of portal venous responses using this model require longer periods of perfusion. This study was designed to determine if this model is suitable for the assessment of hepatic arterial and portal venous vascular responses over a 5-hr perfusion period. Hepatic arterial responses were consistent to all agents during 5 hr of perfusion. Portal venous responses to the direct smooth muscle acting agents, sodium nitroprusside and adenosine, were constant, but the vasoconstrictor responses to acetylcholine and adenosine 5'-triphosphate (agents that cause an endothelium-independent vasoconstriction and an endothelium-dependent vasodilatation) were potentiated. Coarse measurements of liver function were also performed and suggested that the liver remained viable for the 5 hr of perfusion. These results suggest a decrease in the ability of the endothelium of the portal venous vasculature to respond to vasoactive substances as duration of perfusion increases. The possible reasons for this are discussed.

Acetylcholine↗

Potential sources of sugar for the phlebotomine sandfly Lutzomyia youngi (Diptera: Psychodidae) in a Colombian coffee plantation.

Sugar-deprived Lutzomyia youngi were exposed to each of the five most numerous plant species in a Colombian coffee plantation for 24 h and then tested for the presence of fructose by the cold anthrone assay. Many flies exposed to coffee (Coffea arabica) (up to 55% in an individual test) and guamo (Inga edulis) (up to 28.0%) gave positive results. Although some flies also took sugar from red-flowered balsam (Impatiens balsamina) and bamboo (Bambusa angustifolia), none of the insects exposed to plantain (Musa paradisiaca) gave a positive result unless the plants were infested with aphids (Pentalonia sp.). Although sandflies were successfully marked in the laboratory by exposing them to coffee and guamo plants whose roots had been treated with RbCl at 5000 p.p.m., RbCl was not detected by atomic emission spectrometry in wild specimens caught in the vicinity of RbCl-labelled coffee and guamo.

Animals↗

Areas of the United States with elevated screening levels of 222Rn.

As part of an Environmental Protection Agency/State cooperative program, 38 of the 48 contiguous states have successfully conducted probability-based surveys of indoor 222Rn. These surveys produced short-term screening measurements in approximately 55,000 randomly selected houses. An objective common to all surveys was to identify geographic regions within the state with elevated screening levels of 222Rn. This paper examines the survey results as they relate to this objective. The 38 states were partitioned into 225 geographic regions and summary statistics of 222Rn concentrations (e.g., arithmetic mean, geometric mean, percentage of houses exceeding a specified level) and associated 95% confidence intervals were calculated for each region. Twenty-four of the 225 regions had arithmetic means exceeding 222 Bq m-3 (6 pCi L-1); these are analyzed in detail.

Air Pollutants, Radioactive↗