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Biomedical subjects

M Ruiz

Publications and source records attributed to M Ruiz.

At least 127 records · Page 7Linked to original sources
PubMed1997

Myocardial uptake and redistribution of 99mTc-N-NOET in dogs with either sustained coronary low flow or transient coronary occlusion: comparison with 201Tl and myocardial blood flow.

BACKGROUND: 99mTc-N-NOET (NOET) is a new myocardial perfusion imaging agent that redistributes over time. We sought to better define the redistribution kinetics of NOET using open-chest canine models of sustained low coronary flow (protocol 1) and transient coronary occlusion followed by reflow (protocol 2). METHODS AND RESULTS: In protocol 1 (n=10), NOET and 201Tl were injected during low flow in the left anterior descending coronary artery (LAD) that was sustained for 2 hours. Protocol 2 dogs (n=6) were injected with NOET during 20 minutes of LAD occlusion followed by 2 hours of reflow. In both protocols, serial NOET planar images were acquired, and myocardial flow and 2-hour tracer activities were determined by gamma-well counting. Defect resolution was observed on images in both protocols. Initial defect count ratios, reflecting flow disparity at injection (0.66+/-0.03 and 0.57+/-0.04, respectively), increased over 2 hours (0.73+/-0.02 and 0.75+/-0.04, respectively; P<.001 versus initial). Quantitative imaging showed that NOET redistribution resulted from greater clearance from normal areas versus low-flow or transiently occluded areas. In protocol 1, 2-hour NOET and 201Tl stenotic-to-normal tissue activity ratios were similar (0.76+/-0.06 versus 0.73+/-0.04, P=NS) and higher than injection flow ratios (0.52+/-0.06 and 0.56+/-0.07, respectively, P<.001), consistent with tracer redistribution. In protocol 2, NOET redistributed to an even greater extent (injection flow ratio, 0.27+/-0.04; 2-hour tissue activity ratio, 0.84+/-0.03, P<.001). CONCLUSIONS: NOET is the first 99mTc-labeled myocardial imaging agent with kinetics similar to 201Tl in experimental models, permitting redistribution imaging. NOET appears to be a promising agent for assessing patients with coronary artery disease.

Animals↗
PubMed1997

Myocardial 99mTc-tetrofosmin uptake during adenosine-induced vasodilatation with either a critical or mild coronary stenosis: comparison with 201Tl and regional myocardial blood flow.

BACKGROUND: Clinical studies have shown a comparable coronary stenosis detection rate between 99mTc-tetrofosmin and 201Tl but with smaller defect magnitudes for 99mTc-tetrofosmin. The goals of this study were to measure the first-pass extraction fraction (EF) of 99mTc-tetrofosmin in canine myocardium and to compare 99mTc-tetrofosmin with 201Tl uptake during adenosine-induced vasodilatation in dogs with various degrees of coronary stenosis. METHODS AND RESULTS: EF was calculated in 4 anesthetized, open-chest dogs after intracoronary administration of 125I-labeled albumin and 99mTc-tetrofosmin. In another 16 dogs with either critical (n=6) or mild (n= 10) left anterior descending coronary artery (LAD) stenoses, 201Tl and 99mTc-tetrofosmin were administered during adenosine infusion (250 microg x kg(-1) x min(-1)). Dogs were killed 5 minutes later, and tracer activities were determined by ex vivo imaging of heart slices and by well counting. Mean 99mTc-tetrofosmin EF was 54.0+/-3.7%. In the 6 critical-stenosis dogs, the LAD-to-left circumflex artery (LCx) microsphere flow ratio was 0.22+/-0.02 with adenosine. The LAD-to-LCx activity ratios were 0.37+/-0.04 for 201Tl and 0.67+/-0.05 for 99mTc-tetrofosmin (P<.01). For the 10 mild-stenosis dogs, the LAD-to-LCx flow ratio was 0.44+/-0.05. The 201Tl activity ratio was 0.58+/-0.04, compared with 0.81+/-0.04 for 99mTc-tetrofosmin (P<.01). Thus, in both groups, 99mTc-tetrofosmin uptake underestimated the flow disparity more than 201Tl. Similarly, magnitudes of ex vivo image defects were significantly greater for 201Tl than for 99mTc-tetrofosmin in both groups. CONCLUSIONS: In this canine model, relative underperfusion with adenosine stress is better resolved with 201Tl than with 99mTc-tetrofosmin and may be explained by the lower EF for 99mTc tetrofosmin. With clinical imaging, greater 201Tl attenuation and redistribution may lessen this advantage.

Adenosine↗
PubMed1997

Effects of dobutamine stress on myocardial blood flow, 99mTc sestamibi uptake, and systolic wall thickening in the presence of coronary artery stenoses: implications for dobutamine stress testing.

BACKGROUND: Although dobutamine stress is used with both 99mTc sestamibi (sestamibi) myocardial perfusion imaging and echocardiography for detecting coronary artery stenoses, the impact of stenosis severity on test end points (myocardial sestamibi uptake and systolic thickening, respectively) has not been clearly defined. METHODS AND RESULTS: In 15 open-chest dogs, dobutamine (2.5 to 30 microg x kg(-1) x min(-1)) was infused after placement of an LAD stenosis that reduced (n=8) or abolished (n=7) flow reserve. In dogs with reduced flow reserve, the stenotic-to-normal sestamibi activity ratio (0.86+/-0.03) significantly underestimated the approximately 2-to-1 dobutamine-induced flow disparity at the time of sestamibi injection (flow ratio, 0.53+/-0.04; P<.001). Stenotic-zone thickening increased at low but not at higher doses of dobutamine (2.9+/-0.4 versus 4.2+/-0.4 mm in normal zone at peak dobutamine; P=.055) but did not fall below baseline (2.7+/-0.3 mm). Similarly, in dogs with absent flow reserve, the sestamibi activity ratio (0.78+/-0.02) underestimated the approximately 2.5-to-1 dobutamine-induced flow disparity (flow ratio, 0.41+/-0.05; P<.001), and failure to increase systolic thickening was observed in the stenotic zone (2.7+/-0.4 versus 4.6+/-0.3 mm in the normal zone at peak stress, P<.01). In both groups of dogs, myocardial sestamibi uptake and image defect magnitudes were less than expected for the dobutamine-induced hyperemia, suggesting that dobutamine adversely affects myocardial sestamibi binding. Finally, a significant reduction in stenotic-zone thickening was seen during postdobutamine recovery, consistent with myocardial stunning. CONCLUSIONS: In the presence of stenoses that reduced or abolished regional flow reserve, (1) myocardial sestamibi uptake significantly underestimated the dobutamine-induced flow heterogeneity, (2) a "failure to increase systolic thickening" rather than a reduction in thickening was observed during dobutamine stress, and (3) myocardial stunning was observed during postdobutamine recovery.

Analysis of Variance↗
PubMed1997

Implantation of colon cancer at trocar sites is increased by low pressure pneumoperitoneum.

BACKGROUND: The purpose of this study was to determine the effect of pneumoperitoneum on the implantation of tumor at trocar sites. METHODS: GW-39 human colon cancer cell suspension (0.5 ml of 2.5% v/v) was injected into the peritoneal cavity of golden Syrian hamsters through a 1 cm midline incision. Four 5 mm trocars were inserted through the anterior abdominal wall, and the midline incision was then closed. The animals were randomized to receive pneumoperitoneum (n = 62) or no pneumoperitoneum (n = 60) for 10 minutes. Tumor implantations at trocar sites and midline wound incisions were documented grossly and histologically 8 weeks later. RESULTS: Tumor was identified in 86% (49 of 57) of control animals and 95% (52 of 55) of the experimental group (p = 0.20). Implants increased with pneumoperitoneum at the midline incision from 44% to 71% (p < 0.01) and at trocar sites from 41% to 64% (p < 0.00001). CONCLUSIONS: Pneumoperitoneum significantly increased tumor implantation at trocar sites and midline incisions.

Animals↗
PubMed1997

Time trend and age-period-cohort effects on gastric cancer incidence in Zaragoza and Navarre, Spain.

STUDY OBJECTIVE: To describe time trends in gastric cancer incidence in Zaragoza and Navarre, and to investigate time period and birth cohort as determinants of such trends. DESIGN: Cases from two registries were grouped into five year intervals and the following were calculated: age specific and sex specific incidence rates, and the male to female ratio. Log linear models including age, period of diagnosis, and birth cohort were fitted. SETTING: The Zaragoza Cancer Registry covers the province of Zaragoza, which has a population of 824,776 (403,755 men and 421,021 women). The Navarre Cancer Registry covers the province of Navarre which has 512,512 inhabitants (254,786 men and 257,726 women). In both cases population figures were based on the late census. PATIENTS: These comprised incident cases of gastric cancer reported to the Zaragoza Cancer Registry in 1963-87 and to the Navarre Cancer Registry in 1973-87. MAIN RESULTS: Navarre registered higher adjusted and cumulative rates than Zaragoza for both sexes. In both provinces, there were relative declines in the rates for men and women of 3% and 4% respectively per year. In Zaragoza, the risk of developing stomach cancer fell in generations born between 1888 and 1933, and rose in subsequent birth cohorts in both sexes, while in Navarre the cohort effect showed an approximately linear risk for both sexes. Both provinces recorded increases in risk associated with cohorts born between 1933 and 1943. CONCLUSION: The incidence rates of gastric cancer fell in both Zaragoza and Navarre. The reason for the greater incidence of gastric cancer in Navarre remains unknown. Trends in rates seem to be mainly linked to birth cohort. Increases in risk in generations born after 1933 may be ascribable to nutritional deficiencies in the early years of life.

Adolescent↗
PubMed1997

Community-acquired pneumonia in the elderly. Clinical and nutritional aspects.

Community-acquired pneumonia (CAP) in the elderly has a different clinical presentation than CAP in other age groups. Confusion, alteration of functional physical capacity, and decompensation of underlying illnesses may appear as unique manifestations. Malnutrition is also an associated feature of CAP in this population. We undertook a study to assess the clinical and nutritional aspects of CAP requiring hospitalization in elderly patients (over 65 yr of age). One hundred and one patients with pneumonia, consecutively admitted to a 1,000-bed teaching hospital over an 8-mo period, were studied (age: 78 +/- 8 yr, mean +/- SD). Nutritional aspects and the mental status of patients with pneumonia were compared with those of a control population (n = 101) matched for gender, age, and date of hospitalization. The main symptoms were dyspnea (n = 71), cough (n = 67), and fever (n = 64). The association of these symptoms with CAP was observed in only 32 patients. The most common associated conditions were cardiac disease (n = 38) and chronic obstructive pulmonary disease (COPD) (n = 30). Seventy-seven (76%) episodes of pneumonia were clinically classified as typical and 24 as atypical. There was no association between the type of isolated microorganism and the clinical presentation of CAP, except for pleuritic chest pain, which was more common in pneumonia episodes caused by classical microorganisms (p = 0.02). This was confirmed by a multivariate analysis (relative risk [RR] = 11; 95% confidence interval [CI]: 1.7 to 65; p = 0.0099). The prevalence of chronic dementia was similar in the pneumonia cohort (n = 25) and control group (n = 18) (p = 0.22). However, delirium or acute confusion were significantly more frequent in the pneumonia cohort than in controls (45 versus 29 episodes; p = 0.019). Only 16 patients with pneumonia were considered to be well nourished, as compared with 47 control patients (p = 0.001). Kwashiorkor-like malnutrition was the predominant type of malnutrition (n = 65; 70%) in the pneumonia patients as compared with the control patients (n = 31; 31%) (p = 0.001). The observed mortality was 26% (n = 26). Pleuritic chest pain is the only clinical symptom that can guide an empiric therapeutic strategy in CAP (typical versus atypical pneumonia). Both delirium and malnutrition were very common clinical manifestations of CAP in our study population.

Age Factors↗
PubMed1997

ALDP expression in fetal cells and its application in prenatal diagnosis of X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (X-ALD) is due to an impairment in the peroxisomal beta-oxidation of very long straight chain fatty acids (VLCFAs) and the gene involved encodes a 75 kD protein (ALDP). Prenatal diagnosis is usually made by measurement of VLCFAs in cultured amniotic fluid cells (CAF) and chorionic villus cells (CCV), but some misdiagnoses have been reported. For this reason, some authors suggest the use of more than one strategy to minimize the risk of pitfalls. In this study we show, by immunochemical techniques, that ALDP is expressed in chorionic villi and amniotic cells and can be used for prenatal diagnosis of X-ALD in kindreds where ALDP is absent (69-84 per cent), together with VLCFA determination. Moreover, we demonstrate that the culture medium modifies ALDP expression; therefore, it is a factor that must be taken into account when a prenatal diagnosis is done.

ATP Binding Cassette Transporter, Subfamily D, Mem↗
PubMed1997

Design of access control methods for protecting the confidentiality of patient information in networked systems.

Public awareness of the potential for violation of personal privacy in clinical information systems is increasing. Much of this increase can be attributed to the popularity and publicity of the World Wide Web. Nightly news reports of intruder break-ins and flaws in Internet software security have stimulated public interest in the security of clinical information systems available over the web. As part of the development of systems designed to provide clinical narratives to physicians over the Internet, we are exploring designs that provide additional protection and security to these systems. Specifically, we are developing and testing automated access control measures based on provider-patient relationships for controlling access to personally identifiable patient information.

Computer Communication Networks↗
PubMed1996

Pharmacological stress thallium scintigraphy with 2-cyclohexylmethylidenehydrazinoadenosine (WRC-0470). A novel, short-acting adenosine A2A receptor agonist.

BACKGROUND: Pharmacological stress imaging with adenosine or dipyridamole is associated with a high incidence of side effects, including hypotension, chest pain, AV conduction abnormalities, and bronchospasm. Although the desired coronary vasodilatory response is mediated primarily by the adenosine A2A receptors, these side effects result from stimulation of the A1, A2B, or A3 adenosine receptors. We hypothesized that a selective adenosine A2A receptor agonist would induce coronary vasodilatation appropriate for pharmacological stress imaging, without evoking adenosine receptor-mediated side effects. METHODS AND RESULTS: Infusions of a potent and selective A2A adenosine receptor agonist, WRC-0470 (0.1 to 3 micrograms kg-1. min-1 for 10 minutes), to five open-chest dogs produced dose-related left anterior descending (LAD) and left circumflex (LCx) coronary artery vasodilatation without altering mean arterial pressure, heart rate, left atrial pressure, or left ventricular dP/dt. In the same dogs, adenosine (300 micrograms . kg-1. min-1 for 4 minutes) produced coronary vasodilatation that was limited by significant hypotension. To determine the utility of WRC-0470 for pharmacological stress imaging, the hemodynamic responses to WRC-0470 (0.6 microgram.kg-1.min-1 for 10 minutes) and adenosine (250 micrograms.kg-1.min-1 for 4 minutes) were compared in dogs with critical LAD stenoses. 201T1 was injected at the peak WRC-0470 stress response. WRC-0470 increased LCx flow nearly fivefold but did not significantly lower mean arterial pressure. Anteroseptal defects were readily apparent in slice images from all dogs. The mean defect ratio (LAD/LCx) was 0.59 +/- 0.06. CONCLUSIONS: The potent A2A-selective adenosine receptor agonist WRC-0470 is a short-acting coronary vasodilator with potential utility for pharmacological stress perfusion imaging.

Adenosine↗
PubMed1996

T cell differentiation/maturation of CD34+ stem cells from HIV-seropositive hemophiliacs in cultured thymic epithelial fragments.

The clinical manifestations of AIDS are predominantly due to the cellular and humoral immune dysfunction caused by HIV infection, and thymic dysplasia caused by HIV infection probably contributes to the T cell lymphopenia. In the present study, T cell differentiation and/or maturation was assessed when enriched CD34+ stem cells (SCs or SC) purified from bone marrow of HIV-seropositive hemophiliacs were cocultured with allogeneic cultured thymic epithelial fragments (CTEFs). When HIV-seropositive hemophiliacs' enriched CD34+ SC were cocultured with allogeneic CTEFs, acquisition of the T cell phenotypic markers CD7, CD2, CD3, CD4, CD8 and T cell receptor for antigen (TCR) alpha beta was observed from cells harvested from the culture media peaking at approximately 28 days. Origin of the differentiated and matured T cells from the CD34+ SC was confirmed by labeling the SC with 5-(and -6)-(((4-chloromethyl)benzoyl)amino)tetra-methyl-rhodamine (CMTMR), a fluorescent cytoplasmic dye, and detecting fluorescence in the differentiated and matured T cell by flow cytometry. In one experiment, CMTMR labeling was omitted and double positive CD4+CD8+ and triple positive CD3+CD4+CD8+ thymocytes were identified. These studies confirmed that thymocyte differentiation/maturation from SC had occurred. In addition, T cells obtained from the CD34+ SC and CTEF cocultures proliferated to phytohemagglutinin stimulation maximally with stem cell donor antigen-presenting cells (APCs) and also proliferated to pooled B cells in a mixed lymphocyte culture (MLC). Furthermore, the T cells produced were tolerant to thymus donor B cell HLA antigens (p < 0.025); though there was slight MLC reactivity to autologous stem cell donor B cell HLA compared to thymic B cells (p < 0.025). These T cells demonstrated positive self-alloreactivity to stem cell HLA antigens in four of nine persons, though decreased compared to pool B cell alloantigens. Furthermore, in three experiments, responsiveness to stem cell donor B cells subsequently disappeared upon further duration of CD34+ SC-CTEF coculture. These studies suggested that CD34+ SC gave rise to accessory cells populating the thymus that contributed to HLA restriction. To further evaluate this hypothesis, two different donors of CD34+ SC were cultured simultaneously with thymic epithelial fragments and MLC reactivity was then examined toward APC of the stem cell donors. In these experiments, T cells responded to stimulation with HLA antigens of the pool B cells and did not respond to thymus donor B cells. In six of eight experiments, the chimeric SC-CTEF T cells did not respond to stimulation with B cells of either stem cell donor. These studies suggest that HLA restriction and tolerance were induced by cells of the stem cell donor as well as the thymic epithelial cell HLA antigens. In summary, these studies demonstrated that HIV-infected hemophiliac bone marrow-derived nonadherent CD34+ SC were capable of differentiating and/or maturing into T cells when cocultured in a normal allogeneic thymic environment. Furthermore, the T cells derived from derived CD34+ SC were capable of differentiating into T cells when cocultured in a normal allogeneic thymic environment, proliferated maximally with APCs from the stem cell donor and were tolerant of thymic HLA class II antigens, and to a lesser degree to stem cell donor B cell HLA antigens.

Antigen-Presenting Cells↗
PubMed1996

Reduction of thrombotic and hemorrhagic complications after stent implantation.

This study compared two consecutive antithrombotic strategies after Palmaz-Schatz stent implantation and involved 918 patients. Patients treated between May 1991 and May 1994 (group 1; n = 379) received aspirin, dipyridamole, and intravenous unfractionated heparin until oral anticoagulation was effective, between June 1994 and August 1995, 539 patients (group 2) were treated for 1 month with subcutaneous low-molecular-weight heparin (Fragmin), ticlopidine, and aspirin. There were no differences between the groups in terms of sex, clinical condition, vessel diameter, and severity and location of stenosis. Patients in group 1 were younger than those in group 2 (4% were > 70 years old compared with 12%, respectively; p < 0.01). Group 1 patients had more frequent unplanned stenting (48% vs 18%, respectively; p < 0.01) and fewer endoprostheses in the same artery than those in group 2 (1.1 +/- 0.5 vs 1.2 +/- 0.5, respectively; p < 0.01). Among group 2 patients, there was a significant reduction in thrombotic and hemorrhagic complications compared with group 1 patients. No subacute thrombosis occurred in patients in group 2 in contrast with a 5.8% incidence in patients in group 1 (p < 0.01). In addition, a lower incidence of groin and systemic bleeding was observed in patients in group 2 compared with patients in group 1 (2.6% vs 15%, respectively; p < 0.01). The association of low-molecular-weight heparin and antiplatelets provides a simpler antithrombotic strategy in patients treated with intracoronary stents and reduces the incidence of stent thrombosis and hemorrhagic complications. Our findings suggest that this antithrombotic regimen may prevent or completely avoid stent thrombosis.

Acute Disease↗
PubMed1996

Neutrophil function in elderly persons assessed by flow cytometry.

It is well known that the immune response declines with senescence and it is suggested that these changes render an individual susceptible to infection, autoimmune phenomena and cancer. Bacterial and viral infections are a major cause of illness and death amongst aged subjects, and once infection is established, the elderly also have a diminished capacity to prevent its spread (1). The cellular and molecular basis for this age-related decline in immunocompetence are still unknown and, possibly, are related to an alteration in cell transduction mechanisms (2).

Aged↗
PubMed1996

Increased cell genesis in retinal pigment epithelium of perinatal vitiligo mutant mice.

PURPOSE: To compare cell proliferation in vitiligo and control mouse retinal pigment epithelium (RPE) perinatally. METHODS: C57BL/6J-mivit/mivit mice and congenic +/+ controls were injected once with bromodeoxyuridine 1 hour before they were killed between embryonic day 18 and postnatal day 8. Wholemounts of Carnoy-fixed posterior eyecups, minus lens and neural retina, were stained immunohistochemically to detect DNA synthesis (bromodeoxyuridine incorporation) and mitotic cells (R3 antibody binding). Cells were counted in carefully controlled sampling sites, and total RPE area and face-view cell areas were calculated. Retinal pigment epithelial cell heights were measured on light and electron micrographs. RESULTS: Total surface areas of the mutant and control RPE monolayer were similar (I.E., RPE wholemount area was normal), but cell number was approximately doubled in the mutant RPE. By postnatal day 6, mutant cells had approximately 70% the face-view area as controls, but their heights were increased approximately 80%, so that cell volumes were near normal despite the higher packing density. Regional differences in cell size in the control RPE were absent in the mutant specimens. The mutant RPE showed an increased bromodeoxyuridine labeling index, as well as an absolute increase in the number of cells engaged in DNA synthesis and in mitosis. CONCLUSIONS: Cell genesis in the vitiligo RPE is quantitatively abnormal perinatally, well before the neural retina has been recognized to display functional or morphologic defects. Cells are being generated at an abnormally high rate, so that twice the normal number of cells are packed into a RPE of normal total area.

Animals↗