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Biomedical subjects

L A Gray

Publications and source records attributed to L A Gray.

At least 19 recordsLinked to original sources
PubMed2003

In vitro antiproliferative activity of the farnesyltransferase inhibitor R115777 in hematopoietic progenitors from patients with myelofibrosis with myeloid metaplasia.

R115777 is an orally bioavailable farnesyltransferase inhibitor (FTI) that has displayed encouraging activity in patients with acute myeloid leukemia. To determine whether R115777 might exert similar activity in myelofibrosis with myeloid metaplasia (MMM), we evaluated its effects on circulating myeloid progenitor cells from patients with MMM (n=25) using in vitro colony-forming assays. The median R115777 concentrations that inhibited colony formation by 50% were 34 and 2.7 nM for myeloid and megakaryocytic colonies from MMM patients, respectively. Progenitors from normal controls and patients with other myeloproliferative disorders demonstrated similar sensitivity. Since the ras polypeptides are one putative target of FTIs, the potential role of ras effectors was examined by incubating parallel progenitor assays with the phosphatidyl-inositol-3 (PI-3) kinase inhibitor LY294002 and the mitogen-activated protein kinase 1 inhibitor PD98059. MMM progenitor colonies (n=7) were highly sensitive to LY294002 but not to PD98059, implying that the PI-3 kinase pathway may be critical for survival and proliferation of these cells. In addition to indicating that MMM progenitors are sensitive to clinically achievable R115777 concentrations in vitro, these results provide a potential explanation for the thrombocytopenia observed with R115777 during the treatment of other hematologic malignancies.

Adult↗
PubMed2001

Current status of the AbioCor implantable replacement heart.

BACKGROUND: The AbioCor implantable replacement heart (IRH) has been developed as an alternative to transplant (ie, destination therapy). We report our experience with the AbioCor IRH in a bovine model at the University of Louisville. METHODS: Male Holstein cows were used (85 to 115 kg). The internal controller, battery, and secondary transcutaneous energy transfer coil were implanted in the right flank. After cardiopulmonary bypass, the thoracic unit was implanted orthotopically. After removal of air and weaning from cardiopulmonary bypass, the AbioCor was connected to internal components and energy transfer through transcutaneous energy transfer coils was achieved. RESULTS: Nineteen animals underwent implantation of the AbioCor IRH for a proposed 30-day duration. There were 6 deaths, none related to device malfunction. All animals demonstrated normal hemodynamics with normal pressures in the aorta, pulmonary artery, left atrium, and right atrium. There was no significant hemolysis and all animals demonstrated normal end organ function. The internal battery allowed for brief periods of untethered mobility. CONCLUSIONS: The AbioCor IRH has resulted in normal hemodynamics and normal end organ function without evidence of hemolysis in a bovine model.

Animals↗
PubMed2001

Radiation therapy for symptomatic hepatomegaly in myelofibrosis with myeloid metaplasia.

OBJECTIVE: To describe the experience with liver irradiation in advanced cases of myelofibrosis with myeloid metaplasia (MMM). METHODS: Over a 20-yr period, 14 patients with MMM were treated with a total of 25 courses of liver, abdominal, or abdominal and pelvic irradiation for symptomatic hepatomegaly with (5 patients) or without (9 patients) ascites. All 14 patients had advanced disease and 11 (79%) had previous splenectomy. The median radiation therapy (RT) dose per course was 150 cGy (range 50-1000) administered at a median of six fractions. Four patients received two to six courses. RESULTS: Twelve of the 14 patients (86%) had a transient (median 3 months) subjective response from RT. However, in only 35% of these was there a transient (median 3 months) decrease in palpable liver size. Four of the five patients with ascites experienced a short-term response from RT. Eight of the 13 patients suitable for evaluation (62%) had treatment-associated cytopenia, often in the form of anemia and/or thrombocytopenia. At last follow-up, 10 patients (71%) had died after a median of 7 months (range 0.1-23) and 4 were alive at 3, 20, 33, and 57 months after RT. CONCLUSIONS: Low-dose abdominal RT for symptomatic hepatomegaly or ascites associated with advanced-stage MMM is myelosuppressive and provides only temporary and mainly subjective and short-lived relief.

Abdomen↗
PubMed2001

A phase II trial of pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone), a novel anti-fibrosing agent, in myelofibrosis with myeloid metaplasia.

The anti-fibrotic and cytokine modulatory properties of pirfenidone suggest its usefulness in the treatment of myelofibrosis with myeloid metaplasia (MMM). In a prospective study, 28 patients with MMM were treated with oral pirfenidone. Twelve patients completed 1 year of therapy; 13 were withdrawn because of disease progression and three because of drug intolerance. Only one patient experienced a clinically relevant benefit with respect to anaemia and splenomegaly. The overall lack of clinical benefit correlated with no significant improvement in the bone marrow morphological features of the disease. We conclude that pirfenidone has no significant clinical or biological activity in MMM.

Administration, Oral↗
PubMed2000

Fructose-1,6-diphosphate and a glucose-free solution enhances functional recovery in hypothermic heart preservation.

BACKGROUND: Fructose-1,6-diphosphate (FDP) has been shown to protect tissue during hypoxia under various ischemic conditions, including isolated heart perfusion. We tested the hypothesis that adding FDP to St. Thomas solution can extend hypothermic heart preservation time. METHODS: Sixteen adult Sprague-Dawley rats were used. Under general anesthesia, the hearts were removed and preserved at 4 degrees C in St. Thomas solution (30 ml/kg) for 12 hours. FDP (5 mM) was added to the St. Thomas solution in the study group (n = 8), whereas no FDP was used in the control group (n = 10). The hearts were reperfused after 12 hours of preservation using a working heart model. RESULTS: In the study group, cardiac output ranged from 13.00 +/- 2.34 to 17.66 +/- 1.71 ml/min, maximum aortic flow was 3.40 +/- 1.99 to 9.26 +/- 1.72 ml/min, left ventricular stroke volume ranged from 0.074 +/- 0.014 to 0.092 +/- 0.009 ml, left ventricular stroke work ranged from 6.22 +/- 0.39 to 7.95 +/- 0.44 ml/mmHg, and maximum left ventricular generated power was 14.38 +/- 2.94 to 20.16 +/- 2.49 Joules/min. All of these parameters were higher than those in the control group (p < 0.001). Coronary vascular resistance and myocardial tissue wet/dry weight ratio were lower in the study group than in the control group (p < 0.05). CONCLUSIONS: Heart function was better preserved when FDP was added to St. Thomas solution during hypothermic rat heart preservation. The mechanism is not totally clear, but enhancement of high-energy phosphate production during ischemia is possible. Key words: heart, procurement, hypothermia, fructose-1,6-diphosphate.

Animals↗
PubMed1999

Acute cardiovascular changes of partial left ventriculectomy without mitral valve repair.

We assessed the acute cardiovascular changes of partial left ventriculectomy (PLV) in a patient with idiopathic dilated cardiomyopathy (IDCM) without mitral regurgitation. Acutely, PLV reduced left ventricular (LV) end-diastolic dimension and volume while increasing LV ejection fraction and cardiac output due to increased HR and SV. Substantial increases in LV filling pressure, possibly due to high LV end-systolic and diastolic elastances, were of concern clinically and the mechanism(s) of change remain unclear. However, one year follow-up showed remarkable improvements in NYHA and VO2 max while maintaining reduced LV volume, increased LVEF, and trivial MR.

Cardiomyopathy, Dilated↗
PubMed1999

Results after partial left ventriculectomy versus heart transplantation for idiopathic cardiomyopathy.

OBJECTIVE: Partial left ventriculectomy has been introduced as an alternative surgical therapy to heart transplantation. We performed a single-center, retrospective analysis of all patients with idiopathic dilated cardiomyopathy who underwent partial left ventriculectomy or heart transplantation or who were listed for transplantation to determine operative mortality rate, 12-month survival, freedom from death on the heart transplantation waiting list, and freedom from death or need for relisting for heart transplantation. METHODS: Patients who had partial left ventriculectomy (October 1996 to April 1998) were retrospectively compared with patients who were listed for heart transplantation (January 1995 to April 1998). Survival was assessed after the surgical procedure (partial left ventriculectomy vs heart transplantation) and from time of listing for heart transplantation to assess the additional impact of waiting list deaths. Freedom from death or relisting for heart transplantation was also compared. RESULTS: There was no difference in age or United Network for Organ Sharing status between the 2 groups. Twenty-nine patients with idiopathic dilated cardiomyopathy were listed for heart transplantation; 17 patients underwent transplantation, 6 patients died while on the waiting list, and 6 patients remain listed. One patient died after heart transplantation, and 1 patient required relisting. Sixteen patients had partial left ventriculectomy; 10 patients are in improved condition, 2 patients died (1 death early from sepsis and 1 death from progressive heart failure), and 4 patients required relisting for heart transplantation. Operative survival was 94% after partial left ventriculectomy and 94% after heart transplantation (P =.92). Postoperative 12-month Kaplan-Meier survival was 86% after partial left ventriculectomy and 93% after heart transplantation (P =.90). Twelve-month Kaplan-Meier survival after listing for heart transplantation was 75% due to death while on the waiting list (P =.76). Freedom from death or need for relisting for heart transplantation was 56% after partial left ventriculectomy and 86% after transplantation (P =.063). CONCLUSION: Operative and 12-month survival after partial left ventriculectomy and heart transplantation were comparable. However, despite their initial improvement, many patients who underwent partial left ventriculectomy required relisting for transplantation. Although partial left ventriculectomy is associated with acceptable operative and 12-month survival, it may prove to serve better as a bridge to transplantation in patients with idiopathic dilated cardiomyopathy rather than definitive therapy, given the number of patients who required relisting for transplantation.

Adult↗
PubMed1999

Nigerian university students' knowledge, perceptions, and behaviours about HIV/AIDS: are these students at risk?

The purpose of the study was to determine the knowledge level of undergraduate students of a Nigerian university about HIV/AIDS, their perception of risk of contracting HIV/AIDS based on their sexual behaviour, and to assess how students acquire information about HIV/AIDS. The sample consisted of 380 students from five faculties of the university who volunteered to participate in the study. Participants completed a survey asking about their knowledge about transmission, symptomatology and prevention of HIV/AIDS. The survey included questions about their sexual orientation, past and present sexual practices as well as sources of information about HIV/AIDS. The results indicated that the students were knowledgeable about transmission and symptomatology but there were some misconceptions about the mode of transmission of HIV. Few students identified themselves to be at high risk even though majority of them (92%) were sexually experienced. The study also showed that even though these students are knowledgeable and concerned about contracting HIV/AIDS from their partners, this did not prevent them from engaging in unprotected sexual intercourse. It appears, however, that students are exercising caution when negotiating new sexual relationships, as they are likely to discuss (and insist on) using condoms and ask to have a monogamous relationship. Students obtained information about HIV/AIDS primarily from the media rather than from school classrooms and homes, which suggests a need to increase educational efforts at the university. Many students of this university may be at risk of becoming HIV-infected due to their age bracket, level of sexual activity and past/present sexual behaviors. University faculty can be actively involved in developing and implementing HIV/AIDS education and prevention strategies on their campuses. Health educators must go beyond providing accurate and gender-specific information about HIV/AIDS; they must also help students realistically assess their own risk of infection, and develop communication processes which enable them to negotiate safer sexual practices.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Role of graft flow measurement technique in anastomotic quality assessment in minimally invasive CABG.

BACKGROUND: Anastomotic quality is currently the critical issue in minimally invasive coronary surgery. Although little is known about its effectiveness, surgeons routinely assess grafts intraoperatively using flow probes. This study was designed to determine whether mean flow and the pattern of flow tracing in internal mammary artery grafts obtained with a transit-time flow probe are reliable indicators of anastomotic quality. METHODS: Mongrel dogs (n = 14, 30 to 35 kg) underwent off-pump left, right, or left and right internal mammary artery to left anterior descending artery anastomosis (23 grafts). Moderate to severe degrees of stenosis were created at the anastomosis by an additional suture. Internal mammary artery graft flow was measured before and after the stenosis was created with the left anterior descending artery occluded. Angiography was performed at random postoperatively to validate the degree of stenosis. Mean flow and flow tracing morphology were compared under various degrees of stenosis. RESULTS: There were no significant differences in mean graft flow or the morphology of the flow tracing between patent (<15%), mild (<25%), moderate (<50%), and moderately severe (<75%) stenosis. However, mean graft flow decreased (p < 0.05) with severe stenosis (>75%). CONCLUSIONS: Although differences in mean graft flow and graft flow morphology were detectable in anastomoses with severe stenosis (>75%), they were indistinguishable in anastomoses with mild (<25%) to moderately severe (<75%) stenosis. Flow measurement techniques are valuable tools intraoperatively, but surgeons should exercise caution in their interpretation.

Anastomosis, Surgical↗
PubMed1998

Clinical experience with the video-assisted saphenectomy procedure for coronary bypass operations.

BACKGROUND: Leg wound complications after saphenectomy are frequent after coronary bypass operations and have a detrimental effect on postoperative quality of life and treatment cost. To reduce morbidity, we evaluated a new technique of video-assisted vein harvest. METHODS: Between March 1996 and October 1996, 50 patients had video-assisted saphenectomy (VAS) and 40 patients had the standard open technique (control group). An additional 13 patients had both procedures (hybrid group). Level of pain, edema, and wound complications were evaluated at discharge and at 2, 4, and 6 weeks postoperatively. RESULTS: The mean operating time for VAS patients was slightly higher than for control (60.6+/-24.7 minutes versus 53.2+/-21.1 minutes; p > 0.05). The average incision length in VAS patients was 13.8+/-8.8 cm for an average of 3.3 grafts per patient. Three VAS procedures were aborted, two because of time constraints, and one because of bleeding, and a segment of vein was lost to injury. The VAS group had considerably less early postoperative pain than the control group (1.7+/-1.2 versus 4.1+/-1.4 [1 = mild, 10 = severe]; p < 0.005) and edema was similar for both groups. Patients in the hybrid group reported less pain in the VAS-operated leg. Serious wound infection occurred in 4 patients, with 2 patients in the control group requiring reoperation for drainage and flap reconstruction. CONCLUSIONS: Based on this initial experience, VAS harvesting, although initially more time consuming, is a rapidly mastered technique, results in shorter overall incision length, and is associated with considerably less postoperative pain than the standard open technique.

Coronary Artery Bypass↗
PubMed1998

Double grafting of the left anterior descending artery: is the distance between the internal mammary artery and supplemental vein graft anastomoses relevant in graft survival?

INTRODUCTION: Under certain conditions (small internal mammary artery (IMA) or large runoff), double grafting of the left anterior descending (LAD) artery system is necessary to avoid the ominous consequences of myocardial hypoperfusion. Previous studies have shown that a saphenous vein (SVG) adjacent to an IMA graft leads to failure of the IMA. This study compares IMA flow patterns when adjacent ( < 1 cm) and separated (3-4 cm) from a SVG placed on a proximally occluded LAD. METHODS: A SVG and right IMA (PIMA) to proximal LAD (2.5-3 mm) coronary bypass were performed in 12 mongrel dogs. The left IMA (DIMA) was anastomosed to the distal LAD (1.5 mm). All anastomoses were carried out without cardiopulmonary bypass. The native LAD was occluded proximally to the PIMA anastomosis, and all graft flows were measured in competitive and non-competitive flow conditions. RESULTS: Isolated graft to LAD flows were similar for the three conduits. There was a drop in flow in both the PIMA and DIMA when placed in competition with the SVG (10.1+/-3.0 vs. 19.1+/-4.6 ml/min; P < 0.05). The total drop in flow was significantly greater in the PIMA (67.6 vs. 39.9%; P < 0.05). Diastolic flow was better preserved in the distal IMA graft (19.6 + 5.6 vs. 10.2+/-3.0 ml/min; P < 0.05). The patterns of flow were much different during competition and there was significant retrograde systolic flow in all PIMA grafts while there was no (n = 5) or minimal retrograde flow (n = 7) in the DIMA grafts. CONCLUSION: An IMA graft, when adjacent to a SVG, sustains a significant decrease in both total and diastolic flows and develops an oscillating pattern of flow in early systole (retrograde then antegrade). Placing the IMA more distally on the LAD improves flow and decreases retrograde flow. In clinical situations requiring double grafting on the LAD, distance between grafts may be an important factor in maintaining IMA patency.

Analysis of Variance↗
PubMed1998

Guiding the way.

Explore the source record for details and available documents.

Humans↗
PubMed1998

Results of partial left ventriculectomy in patients with end-stage idiopathic dilated cardiomyopathy.

BACKGROUND: Partial left ventriculectomy has been recently introduced as a surgical therapy for end-stage heart failure. We performed a prospective study of partial left ventriculectomy in patients with end-stage idiopathic dilated cardiomyopathy (IDCM). METHODS: Patients considered as candidates for partial left ventriculectomy had IDCM, left ventricular end-diastolic diameter greater than 7 cm (LVEDD), refractory New York Heart Association class IV symptoms (NYHA), and severely impaired exercise oxygen consumption. All patients underwent a complete heart transplantation evaluation. RESULTS: Partial left ventriculectomy was performed in 16 patients with a mean follow-up of 11.1 months. Fourteen patients were male with a mean age of 49.6+/-10.5 years. After surgery there were significant changes in NYHA class, left ventricular ejection fraction, LVEDD, and degree of mitral regurgitation at up to 12 months follow-up. The operative mortality rate was 6.25% and 12-month Kaplan-Meier was 86%. Twelve-month freedom from need for listing for orthotopic heart transplantation was 65%. CONCLUSION: Partial left ventriculectomy can be performed in patients with idiopathic cardiomyopathy with acceptable operative and 12 month survival rates. Significant improvements are seen in ejection fraction, LVEDD, and NYHA class at 12 month follow up. Late failures do occur and some patients have required relisting for transplant after partial left ventriculectomy.

Adult↗
PubMed1997

Evolution of forelimb movement patterns for prey manipulation in anurans.

Unlike other amphibians, frogs often use their forelimbs to capture and transport prey. In the present study, high-speed videography was used to observe forelimb use during feeding in a diverse group of anurans in order to determine the evolution of forelimb movement patterns among anuran taxa. Data were gathered from 488 individuals representing 104 species, 55 genera, and 16 families. Five distinct behavior patterns were identified: scooping entails using the back of the hand to push prey into the mouth; wiping involves the use of the palm of the hand to push prey, protruding laterally from the mouth, toward the midline; during prey stretching, one end of the prey is held in a stationary position by the hands while the other end is pulled upward by the jaws; in grasping, the palms face the midline or the substrate as the fingers are wrapped around the prey; grasping with wrist rotation is similar to grasping, but the wrists rotate inward as the hands grasp the prey so that the palms face the mouth. The distribution of these behavior patterns was mapped onto the most recent phylogenetic hypothesis for anurans. Maximum parsimony analyses suggest that scooping and wiping are primitive and have been retained by many frog lineages. Wiping was not observed in the pipids, which are the only anurans that lack tongues and use hydraulic transport. Prey stretching appears to have evolved several times in unrelated taxa. Grasping and grasping with wrist rotation appear to have evolved only in arboreal groups, suggesting that the ability to climb is a preadaptation for the ability to grasp prey. Several species were observed using grasping motions in place of the tongue to capture prey.

Animals↗
PubMed1997

Preoperative and postoperative comparison of patients with univentricular and biventricular support with the thoratec ventricular assist device as a bridge to cardiac transplantation.

OBJECTIVES: The goal of this study was to determine whether there are differences in populations of patients with heart failure who require univentricular or biventricular circulatory support. METHODS: Two hundred thirteen patients who were in imminent risk of dying before donor heart procurement and who received Thoratec left (LVAD) and right (RVAD) ventricular assist devices at 35 hospitals were divided into three groups: group 1 (n = 74), patients adequately supported with isolated LVADs; group 2 (n = 37), patients initially receiving an LVAD and later requiring an RVAD; and group 3 (n = 102), patients who received biventricular assistance (BiVAD) from the beginning. RESULTS: There were no significant differences in any preoperative factors between the two BiVAD groups. In the combined BiVAD groups, pre-VAD cardiac index (BiVAD, 1.4 +/- 0.6 L/min per square meter, vs LVAD, 1.6 +/- 0.6 L/min per square meter) and pulmonary capillary wedge pressure (BiVAD, 27 +/- 8 mm Hg, vs LVAD, 30 +/- 8 mm Hg) were significantly lower than those in the LVAD group, and pre-VAD creatinine levels were significantly higher (BiVAD, 1.9 +/- 1.1 mg/dl, vs LVAD, 1.4 +/- 0.6 mg/dl). In addition, greater proportions of patients in the BiVAD groups required mechanical ventilation before VAD placement (60% vs 35%) and were implanted under emergency conditions than in the LVAD group (22% vs 9%). The survival of patients through heart transplantation was significantly better in patients who had an LVAD (74%) than in those who had BiVADs (58%). However, there were no significant differences in posttransplantation survival through hospital discharge (LVAD, 89%; BiVAD, 81%). CONCLUSION: Patients who received LVADs were less severely ill before the operation and consequently were more likely to survive after the operation. As the severity of illness increases, patients are more likely to require biventricular support.

Heart Transplantation↗
PubMed1996

Left ventricular contributions to right ventricular systolic function during LVAD support.

BACKGROUND: In patients with postcardiotomy low cardiac output syndromes, right ventricular (RV) failure develops in approximately 25% of patients receiving left ventricular (LV) assist device support. Depressed RV function have been attributed to abnormalities of the RV myocardium, excessive load imposed on the RV during systole or diastole, or obstruction to RV inflow. However, recent studies also suggest that LV function may significantly affect RV function through ventricular interdependence. METHODS: We reviewed the data showing the importance of systolic ventricular interaction. We then related these observations to the RV response during LV assist device support, and present our ideas regarding the mechanisms responsible for this RV failure. RESULTS: Using an electrically isolated right heart preparation, Damiano observed double-peaked waveforms for RV pressure, and pulmonary artery blood flow occurred over a wide range (0 to 300 ms) of pacing intervals between the LV and RV. Numeric analysis indicated that RV systolic pressure and pulmonary artery blood flow were composed of both RV and LV components, with the LV component dominating (63.5% versus 36.5%). CONCLUSIONS: The experimental studies indicate a very consistent RV response during LV assist device support: a decrease in RV afterload, increased compliance, and decreased contractility. In normal hearts, the net effect is an increase or no change in cardiac output. With a preexisting pathologic condition, the RV responses is qualitatively the same, but anatomic ventricular interaction is accentuated, leading to a greater decrease in RV contractility. The net effect is a decrease in cardiac output, which may require inotropic or RV mechanical support.

Animals↗
PubMed1996

Electrodiagnostic evidence for cervical radiculopathy and suprascapular neuropathy in shoulder pain.

Patients diagnosed with a shoulder impingement syndrome occasionally do not respond to techniques used for treatment of soft tissue injury. The neurologic examination may be only partially abnormal or incomplete due to pain limitation so that peripheral nerve or nerve root abnormalities are overlooked. This study was undertaken to investigate the frequency of cervical radiculopathy and suprascapular neuropathy in patients with shoulder pain who were initially diagnosed with a musculoskeletal syndrome. Thirty-three subjects with a diagnosis of unilateral or bilateral impingement syndrome were entered into the study. A neurological examination was performed, followed by electromyography on 38 upper extremities and associated cervical paraspinal muscles to search for electrodiagnostic evidence for a suprascapular neuropathy and/or cervical radiculopathy. There were no subjects with electrodiagnostic evidence for suprascapular neuropathy. In two studies (5.3%), there was electrodiagnostic evidence for a C5/6 radiculopathy, and in nine (23.7%) additional subjects, there was electrodiagnostic evidence for a possible cervical radiculopathy. The remaining 27 (71.1%) studies showed no significant electrodiagnostic evidence for a cervical radiculopathy. Of the 11 subjects with abnormal electrodiagnostic studies, the neurological examination in 7 (63.6%) was normal except for pain-limited manual muscle testing, and the other 4 (36.4%) had an abnormality in either sensation testing, muscle bulk, or muscle stretch reflexes. One case of a patient with an initial diagnosis of soft tissue injury is presented. In patients undergoing evaluation for shoulder pain, cervical radiculopathy as a possible etiology should be considered, even when there is an equivocal clinical examination.

Adult↗