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Biomedical subjects

G Gray

Publications and source records attributed to G Gray.

At least 19 recordsLinked to original sources
PubMed1992

Amino terminus of the interleukin-8 receptor is a major determinant of receptor subtype specificity.

Interleukin-8 (IL-8) is a key mediator in the migration of neutrophils from the circulation to the site of inflammation in the tissue. IL-8 is secreted by many cell types in response to proinflammatory stimuli such as interleukin 1, tumor necrosis factor, and lipopolysaccharide and is a potent chemoattractant and activator of neutrophils. Neutrophil activating peptide-2 (NAP-2) and melanoma growth-stimulatory activity (MGSA/GRO) are structurally and functionally related to IL-8 and, like IL-8, bind to specific G protein-coupled receptors on neutrophils. In the present study two closely related cloned IL-8 receptor subtypes are characterized by expression of the cDNA clones in monkey kidney cells (COS-7) or chinese hamster ovary cells and analysis of their ligand binding profiles. Both receptor subtypes bind 125I-labeled IL-8 with similar high affinity, however, the F3R receptor binds IL-8 exclusively, while the 4Ab receptor binds both IL-8 and MGSA/GRO with high affinity and NAP-2 with lesser affinity. Furthermore, we demonstrate with the use of intersubtype chimeric receptors that the specificity of ligand binding to both IL-8 receptor subtypes is dictated by the heterogeneous NH2-terminal domain. The F3R receptor is representative of a restricted IL-8 receptor subtype, and 4Ab represents a nonrestricted receptor subtype. It is proposed that these subtypes be named IL-8 receptors alpha and beta, respectively.

Amino Acid Sequence↗
PubMed1992

Mutations in the principal neutralization determinant of human immunodeficiency virus type 1 affect syncytium formation, virus infectivity, growth kinetics, and neutralization.

The principal neutralization determinant (PND) of human immunodeficiency virus type 1 envelope glycoprotein gp120 contains a conserved GPG sequence. The effects of a 29-amino-acid deletion of most of the PND, a 3-amino-acid deletion in the GPG sequence, and 16 single-amino-acid substitutions in the GPG sequence were determined in a transient expression assay. All mutant envelope glycoproteins were expressed at levels comparable to that of the wild-type envelope, and mutations in the GPG sequence did not affect processing to gp120 or, except for the 29-amino-acid deletion, binding to CD4. Of all of the mutants, only the GHG and GFG mutants induced formation of syncytia similar in size and number to those induced by the wild-type envelope. When the envelope expression level was increased 10-fold or more, several additional mutants (APG, GAG, GSG, GQG, GVG, and GPF) also induced syncytium formation. Transfection with infectious proviral molecular clones containing the GHG, GFG, APG, GAG, GSG, or GPF mutations induced production of viral particles; however, only the GPG, GHG, and GFG viruses produced active infections in CD4-bearing cells. Furthermore, whereas the wild-type virus was efficiently neutralized by PND polyclonal and monoclonal antibodies, the GHG- and GFG-containing viruses were not. These results show that mutations in the GPG sequence found within the PND do not affect envelope expression and do not significantly affect CD4 binding or production of viral particles but that they do affect the ability of the envelope to induce syncytia and those of the viral particles to infect CD4 cells and be neutralized by PND antibodies.

Amino Acid Sequence↗
PubMed1992

Pain, opioid use, and survival in hospitalized patients with advanced cancer.

PURPOSE: Pain is a common and feared symptom for patients with incurable cancer. Comprehensive assessment provides the foundation for effective pain management, and data that clarify the relationship between pain and other relevant factors also facilitate this process. The main objective of the study was to develop a clinical data base for advanced cancer patients and to survey data to determine (1) pain severity at admission, (2) opioid use at admission, (3) change in opioid use during the hospital stay, and (4) survival in the hospital. PATIENTS AND METHODS: Information was collected prospectively on 1,103 patients admitted and on 1,017 patients who died within 6 months of the study's end. Demographic and clinical data were recorded 72 hours after admission and soon after death or discharge. RESULTS: Seventy-three percent of patients had pain at admission. Cancer of the cervix was frequently (68%) associated with severe pain, as were prostate (52%) and rectal/sigmoid tumors (49%). Severe pain was more probable in those with bone metastasis, those admitted from home, and in those younger than 55 years of age. The majority (71.7%) of patients had a stable dosing pattern, and only 4.2% of the patients required dose increases of at least 10% per day. CONCLUSION: This study demonstrated the wide variability in opioid doses required. No reliable predictor of opioid requirement was identified, and this lack of predictability of cancer pain severity underscores the need for ongoing assessment.

Adult↗
PubMed1992

Surgical treatment of ventricular tachycardia by balloon electric shock ablation. Potential effects on the mitral valve apparatus.

We have previously described a new surgical technique for control of arrhythmogenic foci in patients with recurrent ventricular tachycardia that we call balloon electric shock ablation. With this method sequential shocks are delivered to a grid of electrodes on a balloon that can be introduced across the mitral valve into the intact ventricle. A series of experiments was undertaken to investigate possible deleterious effects of balloon electric shock ablation when shocks are delivered directly to the mitral valve apparatus. In six animals shocks totaling 1200 joules were given through a closely spaced electrode grid applied to the area of the mitral valve. Nine to 12 weeks later, left ventricular and mitral valve function were assessed. Balloon electric shock ablation in the basilar portion of the ventricle was associated with decreased myocardial performance, as evidenced by ejection phase indices. In five of six animals balloon ablation led to minor thickening of the valve leaflets and chordal attachments plus necrosis of adjacent myocardium, including papillary muscles. In these animals there was no significant dysfunction of the valve observed. In the remaining animal, however, ablation was centered on the posterior papillary muscle and resulted not only in necrosis of the base of the papillary muscle but also in full-thickness scarring and thinning of the adjacent left ventricular wall. In this dog, mitral regurgitation was seen on long-term follow-up. We conclude that when balloon electric shock ablation is used to destroy a localized area of myocardium in the basilar portion of the intact ventricle, the procedure results in decreased myocardial performance. When shocks were directly applied to the mitral valve apparatus in five of six animals, ablation did not result in significant negative effects on the structure and function of the valve. In the sixth dog, however, shock delivery resulted in transmural necrosis and thinning at the site of papillary muscle insertion and was associated with severe mitral regurgitation with volume loading. Therefore caution should be used when considering clinical application of this technique if the area to be ablated is in the basal portion of the heart.

Animals↗
PubMed1990

Hospitalized advanced cancer patients: a profile.

More than half of all individuals diagnosed with cancer will not be cured and will require supportive care for some period. Nonetheless, few large scale studies have documented the prevalence and complexity of the problems of advanced disease. This study examined the demographic treatment and outcome variables for 1,103 admissions to a specialty acute care hospital devoted to the care of patients with advanced cancer. The population is profiled, and significant relationships among these variables are identified. The prevalence of major symptoms is documented. This data base study provides a foundation for further research.

Activities of Daily Living↗
PubMed1990

Cancer in the older adult: understanding age-related changes.

As the population ages, nurses will be working with increased numbers of elderly cancer patients. It is imperative that nurses gain an understanding of the aging process and an appreciation of the cancer experience in the older adult. By aggravating or influencing cancer-related symptoms and their treatments, or by inducing non-cancer related symptoms, concurrent health problems may inadvertently be thought to be associated with malignancy progression. An in-depth investigation of a patient's history may reveal a vast number of actual and potential health problems; the areas that pose special concerns for the elderly are nutrition, pain, and psychosocial aspects, such as depression and confusion.

Aged↗
PubMed1990

Transatrial balloon technique for activation mapping during operations for recurrent ventricular tachycardia.

Results of operations for recurrent ventricular tachycardia have improved since methods of mapping that allow a directed approach to the problem have been developed. With standard operative techniques (ventriculotomy and introduction of a hand-held probe or multiple electrode array), it has not always been possible to obtain satisfactory endocardial activation maps during the tachycardia. We have recently developed a new transatrial balloon approach that has greatly facilitated intraoperative mapping. This paper describes our total experience with the new approach and draws attention to details of the cardiopulmonary bypass technique and the surgical approach needed for safe balloon insertion across the mitral valve. We describe how correlation between position of target electrodes on the balloon and the internal geometry of the heart is achieved and discuss the choice and application of appropriate ablation techniques. In our series of 37 consecutive patients, 35% had a grade IV ventricle (ejection fraction less than 20%), 32% had a previous posterior infarct, 51% did not have a resectable aneurysm, and 54% had been receiving amiodarone within 1 month of the operation. These factors have been associated with poor operative results in other series. With the transatrial balloon technique, we were able to induce and map ventricular tachycardia in 100% of patients (average 2.6 +/- 1.3 morphologies per patient). Using a variety of ablation techniques (endocardial excision, cryoablation, or balloon electric shock ablation), we have achieved surgical control of the arrhythmias in 84% of patients with an operative mortality rate of 14%. We recommend transatrial balloon mapping as the procedure of choice for intraoperative identification of arrhythmogenic foci in patients with recurrent ventricular tachycardia.

Catheterization↗
PubMed1989

Villous tumors of the ampulla of Vater: local resection versus pancreatoduodenectomy.

Villous adenomas involving the ampulla of Vater are uncommon. In particular, malignant potential of villous tumors may be difficult to determine preoperatively. In such cases, the decision to perform a conservative local excision or the more radical pancreatoduodenectomy should be based on accurate histologic assessment and the possibility of obtaining adequate margins of resection.

Adenoma↗
PubMed1989

A simplified concept for a bileaflet atrioventricular valve that maintains annular-papillary muscle continuity.

We have developed a simplified concept for a bileaflet atrioventricular prosthesis that can be constructed from a simple sheet of glutaraldehyde preserved pericardium. The valve has no rigid ring or stent and no cloth sewing ring. Insertion of the valve reestablishes normal continuity between the annulus and the papillary muscles. We have replaced the mitral valve in nine dogs using this prosthesis. All valves have been competent with excellent valve opening areas as confirmed by echo-Doppler assessment. Studies up to 4 1/2 months have confirmed excellent hemodynamics and there has been no evidence of early tissue failure. Possible advantages of this simple valve design are improved hemodynamics, ease of construction and insertion, and low cost.

Animals↗
PubMed1989

Balloon electric shock ablation. Effects on ventricular structure, function, and electrophysiology.

We have recently developed a transatrial balloon approach for intraoperative endocardial mapping of ventricular tachycardia, which can be performed in the intact ventricle. In selected patients, we have eliminated the arrhythmia by passing a series of electric currents through specific beads on the balloon array. The goal of this new technique, balloon electric shock ablation, is to create a homogenous scar in the subendocardial target area identified by mapping. Experimental data exist on the effects of catheter delivery of electric discharges to the myocardium, but no data are available on the effects of balloon electric shock ablation. We have performed balloon electric shock ablation in animals (nine cathodal shocks of 100 J given through a 4 cm2 electrode grid). Ventricular function was assessed at 6 weeks and compared with function after a simple ventriculotomy and with function in control animals having no operation. Gated nuclear ventriculograms were obtained during volume loading. Myocardial performance and diastolic pressure volume relationships were determined for the three groups. After balloon electric shock ablation or ventriculotomy, left atrial pressures were increased at similar end-diastolic volumes, which indicated decreased ventricular compliance. The trend reached statistical significance (compared with data from control animals) only in the group undergoing balloon electric shock ablation. Myocardial performance (stroke work index/end-diastolic volume relationship) was unchanged in the three groups. In the long-term balloon electric shock ablation preparation, an electrophysiologic study (including burst pacing) failed to induce ventricular arrhythmias. At 6 weeks, the lesion created by balloon electric shock ablation was a layer of homogenous mature scar with sharply defined borders. There was no evidence of additional injury to the surrounding myocardium or to the mitral valve apparatus. These studies show that delivery of a series of electric shocks through a 1 cm balloon grid of electrodes can create an area of homogeneous, electrically inert scar and that this procedure when performed in healthy dog hearts has no significant effect on the structure and function of the rest of the left ventricle.

Animals↗
PubMed1988

Spontaneous pregnancies and pregnancies as a result of treatment on an in vitro fertilization program terminating in ectopic pregnancies or spontaneous abortions.

Five hundred three patients were accepted for the in vitro fertilization (IVF) program from 1983 to 1986. Two hundred ninety-nine patients had a total of 678 IVF treatment cycles during this period. Eighty-one clinical pregnancies resulted, of which 8 were ectopic pregnancies and 19 spontaneous abortions (group A). During this period 82 patients accepted for IVF became pregnant spontaneously: 44 before treatment and 38 after a failed IVF treatment cycle (group B). Of these, 14 were ectopic pregnancies and 8 were miscarriages. The main indications for acceptance on the IVF program were similar in the two groups if those patients who had a bilateral salpingectomy are excluded from group A. Causative factors for the high ectopic pregnancy rate are discussed. The authors suggest that after embryo transfer, migration of the embryo or embryos into the fallopian tubes occurs more frequently than realized, and the diseased tube is less likely than a normal tube to propel the embryo back into the uterus. The abortion rate in group B was similar to the rate in the general population.

Abortion, Spontaneous↗
PubMed1988

Hydromorphone levels and pain control in patients with severe chronic pain.

To better understand the use of narcotic analgesics, the hydromorphone concentration was measured in serum samples from 43 patients with chronic severe pain who were receiving this drug. At the time of blood sampling, pain intensity, mood, and cognitive performance were assessed. There was large individual variation in the dose-drug level relationship. Seven patients with bone or soft tissue pain and drug levels of greater than or equal to 4 ng/ml had good pain control, whereas 10 did not. None of 15 patients with levels less than 4 ng/ml had pain control, despite drug doses similar to those given patients with higher levels. Thus 60% of the patients without control of their pain had hydromorphone levels below the lowest level that produced pain control. No patient with pain from nerve infiltration or compression had good pain control, irrespective of the drug level or dose. Poor mood correlated with high pain intensity and low drug level. Impaired cognitive performance was not related to drug level. Knowing that there is a low concentration of narcotic in the blood of a patient with chronic severe pain who is receiving high drug doses and who shows lack of both efficacy and side effects may reassure health care professionals that further narcotic dosage escalation is appropriate.

Adult↗
PubMed1988

A new intraoperative approach for endocardial mapping of ventricular tachycardia.

Results of operation for control of ventricular tachycardia have improved since endocardial mapping techniques have been developed that allow a directed approach to the problem. In some patients, a limitation of established techniques has been difficulty in initiating the arrhythmia after a ventriculotomy has been made to allow introduction of endocardial recording electrodes. This paper describes a transatrial approach for endocardial mapping with a balloon array of 112 electrodes, which has been used intraoperatively in 15 patients. Surgical success in this group has been compared to that obtained in a similar group of patients in whom standard techniques of intraoperative mapping were used. With our new balloon technique we have been able to easily induce and map multiple episodes of ventricular tachycardia in all cases. On the basis of detailed endocardial maps, the locations of earliest activation and possible reentry loops have been identified and ablated with either endocardial excision or application of the cryoprobe. When indicated, concomitant procedures including aneurysm resection (9/15) and bypass grafting (14/15) have been performed. Hospital mortality in this group was 20%. None of the deaths have been related to recurrent ventricular tachycardia or complications of the mapping technique. Postoperative electrophysiologic studies performed at 2 weeks have been normal in 11 of 12 or 92% of patients. To date (mean follow-up 12 +/- 6 months) there has been no clinical recurrence or evidence of ventricular tachycardia by Holter monitoring in these patients. We conclude that the transatrial balloon approach to endocardial mapping facilitates intraoperative induction of ventricular tachycardia, allows complete mapping during multiple runs of the arrhythmia without prolonging cardiopulmonary bypass time, and improves results of operation using standard ablation techniques.

Cardiac Pacing, Artificial↗