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Biomedical subjects

D Payne

Publications and source records attributed to D Payne.

At least 73 records · Page 4Linked to original sources
PubMed1999

Inhaled NO impacts vascular but not extravascular compartments in postischemic peripheral organs.

Inhaled nitric oxide (NO) reduces pulmonary hypertension and dampens various aspects of lung inflammation; however, its effects are thought to be restricted to the lung because of its short half-life in biological systems. More recently, however, NO was shown to nitrosylate hemoglobin, albumin, and other plasma molecules to form stable nitrosothiol derivatives and could have an impact on the periphery. We examined whether inhaled NO could have an impact on the two compartments of distal organs, namely, the intravascular and extravascular spaces. The feline intestine was exposed to 1 h of ischemia and 1 h of reperfusion, and intestinal blood flow and mucosal dysfunction were measured in animals ventilated with room air and inhaling 0 or 80 ppm NO. A decrease in intestinal blood flow and an increase in mucosal barrier leakiness were noted in animals not exposed to inhaled NO. The intestinal blood flow impairment was entirely reversed in animals breathing 80 ppm NO, but the mucosal dysfunction was not affected. We further examined whether inhaled NO could reach the extravascular space by simply inhibiting NO in the intestine with the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) that causes an increase in mucosal permeability that is rapidly reversed with NO donors. However, inhaled NO had no effect on the rise in mucosal permeability. L-NAME reduced lymph nitrosothiol concentrations, but inhaled NO could not replenish these levels. To further explore the intravascular impact of inhaled NO, we used intravital microscopy to visualize the microvasculature and demonstrated that inhaled NO could be initiated after reperfusion and still reduced microvascular disturbances, including reversing the impairment in blood flow and increasing leukocyte adhesion. The effects of inhaled NO persisted for an additional hour after termination of NO inhalation, consistent with a dramatic increase in nitrate within 1 h of NO inhalation, which persisted for 1 h after the termination of NO inhalation. These data suggest that inhaled NO can reach distal organs to dramatically improve reperfusion-induced microvascular but not extravascular dysfunction.

Administration, Inhalation↗
PubMed1999

Inhaled NO reaches distal vasculatures to inhibit endothelium- but not leukocyte-dependent cell adhesion.

Nitric oxide (NO), in addition to being a potent vasodilator, also prevents leukocyte adhesion in the microvasculature. Based on the antiadhesive properties of NO and work suggesting that NO is transported by proteins in the circulation, we tested the possibility that inhaled NO could impart antiadhesive effects in peripheral microvessels. We also determined the underlying mechanisms of actions. Three well-established models that induce local microvascular changes (either endothelium or leukocyte) were used. Hydrogen peroxide (H(2)O(2); 100 microM) was superfused onto the cat mesentery to induce an endothelium-derived, P-selectin- and platelet-activating factor-dependent, oxidant-dependent leukocyte recruitment. In a second series of experiments, the cat mesentery was superfused with histamine (100 microM) to induce rapid endothelium-derived, P-selectin- and platelet-activating factor-dependent, oxidant-independent leukocyte recruitment. Finally, in a third series of experiments to target the leukocyte (but not the endothelium) directly in the periphery, the chemotactic molecule leukotriene B(4) (20 nM) was superfused onto the cat mesentery. The above experiments were performed with and without cats breathing NO (80 parts/million). Intravital microscopy was used to visualize the mesenteric microcirculation. Inhaled NO reduced the increased leukocyte rolling and adhesion associated with H(2)O(2) superfusion of the feline mesentery via a cGMP-dependent mechanism. In contrast, inhaled NO had no effect on the histamine-induced increase in leukocyte rolling flux but partially inhibited the subsequent adhesion. The leukocyte chemotactic mediator leukotriene B(4) induced a significant increase in leukocyte adhesion, but NO inhalation did not impair this chemotactically induced leukocyte recruitment. These data suggest that inhaled NO can reach the endothelium in the distal microvasculature and alter the response to an oxidative and a nonoxidative activator of endothelium but imparts no antiadhesive effect directly on circulating leukocytes.

Administration, Inhalation↗
PubMed1998

Inhaled NO as a viable antiadhesive therapy for ischemia/reperfusion injury of distal microvascular beds.

Inhaled nitric oxide (NO) is being used more and more in intensive care units as a modality to improve the outcome of patients with pulmonary complications. Our objective was to demonstrate that inhaled NO could impact upon a distally inflamed microvasculature-improving perfusion, leukocyte adhesive interactions, and endothelial dysfunction. Using intravital microscopy to visualize ischemia/reperfusion of postcapillary venules, we were able to demonstrate that the reduction in perfusion, the dramatic increase in leukocyte rolling, adhesion, and emigration, and the endothelial dysfunction could all be significantly abrogated with 80 ppm, but not 20 ppm inhaled NO. Perfusing whole blood directly over an inert P-selectin and CD18 ligand substratum incorporated in a flow chamber recruited the same number of rolling and adhering leukocytes from NO-ventilated and non-NO-ventilated animals, suggesting that inhaled NO was not directly affecting leukocytes. To demonstrate that inhaled NO was actually reaching the peripheral microvasculature in vivo, we applied a NO synthase inhibitor locally to the feline mesentery and demonstrated that the vasoconstriction, as well as leukocyte recruitment, were essentially abolished by inhaled NO, suggesting that a NO-depleted peripheral microvasculature could be replenished with inhaled NO in vivo. Finally, inhaled NO at the same concentration that was effective in ischemia/reperfusion did not affect vascular alterations, leukocyte recruitment, and endothelial dysfunction associated with endotoxemia in the feline mesentery. In conclusion, our data for the first time demonstrate a role for inhaled NO as a therapeutic delivery system to the peripheral microvasculature, showing tremendous efficacy as an antiadhesive, antivasoconstrictive, and antipermeabilizing molecule in NO-depleted tissues, but not normal microvessels or vessels that have an abundance of NO (LPS-treated). The notion that blood borne molecules have NO carrying capacity is conceptually consistent with our observations.

Administration, Inhalation↗
PubMed1998

Ethmoid sinus cancer: twenty-nine cases managed with primary radiation therapy.

PURPOSE: To describe the outcome of patients with carcinoma of the ethmoid sinus managed with a policy of primary radiation therapy with surgery for salvage of persistent or progressive disease. METHODS AND MATERIALS: A retrospective chart review was undertaken of 29 patients with the diagnosis of carcinoma of the ethmoid complex who underwent treatment in the period between January 1976 and December 1994 at the Princess Margaret Hospital. Analysis was confined to those patients with epithelial invasive histology (squamous carcinoma, adenocarcinoma, or undifferentiated carcinoma) managed with curative intent with primary radiation therapy. The median patient age was 62, with a median follow-up time of 4 years. Staging was assigned according to a modification of the UICC 1997 system with 19 (66%) of patients presenting with T4 category tumors. The most common radiation dose regimes were 60 Gy in 30 daily fractions over 6 weeks, or 50 Gy in 20 daily fractions over 4 weeks. Outcome was analyzed with respect to overall survival, cause-specific survival, and local progression-free survival. The influence of a variety of clinical and therapeutic factors on outcome is discussed, the patterns of disease failure are described, and the rationale for this treatment approach is outlined. RESULTS: The 5-year rates of overall survival, cause-specific survival, and local progression-free survival were 39%, 58%, and 41%, respectively. A total of 18 of 29 patients died during the period of review. Of these, 12 deaths were due to ethmoid cancer, one was due to a second primary lung cancer, and five were attributed to nononcologic causes. No patients died due to treatment-related toxicity. Increasing T category predicted for worse outcome on univariate analysis. Local progression was the major cause of treatment failure and was documented in 15 of 29 patients treated (52%). Six patients were offered salvage surgery for local progression, of whom two remained disease free at 15 and 17 months follow-up. CONCLUSIONS: Outcome of patients with ethmoid cancer managed with primary radiation therapy with surgery for salvage is comparable to that achieved with planned combined modality approaches. Nevertheless, outcome remains poor and is dependent on the local extent of tumor, with 40-50% of patients eventually succumbing to disease.

Adenocarcinoma↗
PubMed1998

T1/T2 glottic cancer managed by external beam radiotherapy: the influence of pretreatment hemoglobin on local control.

PURPOSE: Pretreatment hemoglobin (Hb) level has been reported to be an important prognostic factor for local control and survival in various malignancies. However, in many settings, the adverse effect of a low Hb may be related to more advanced disease. The purpose of this analysis was to assess the influence of pretreatment Hb on local control in a large series of patients with a localized cancer (T1/T2 glottic cancer, AJCC 1992) treated in a standard fashion. MATERIALS AND METHODS: Between January 1981 and December 1989, 735 patients (median age 63; 657 males, 78 females) with T1/T2 glottic cancer were treated with radiation therapy (RT). The standard RT prescription was 50 Gy in 20 fractions over 4 weeks (97% of patients). Factors studied for prognostic importance for local failure included pretreatment Hb, age, sex, T category, anterior commissure involvement, subglottic extension, and tumor bulk (presence of visible tumor vs. subclinical disease). RESULTS: With a median follow-up of 6.8 years (range 0.2-14.3), 131 patients have locally relapsed for an actuarial 5-year relapse-free rate of 81.7%. The 5-year actuarial survival was 75.8%. The mean pretreatment hemoglobin level was 14.8 g/dl and was similar in all prognostic categories. On multivariate analysis, using the Cox proportional hazards model, pretreatment Hb predicted for local failure after RT. The hazard ratio (HR) for relapse was calculated for various Hb levels. For example, the HR for a Hb of 12 g/dl vs. a Hb of 15 g/dl was 1.8 (95% confidence interval 1.2-2.5). Previously established factors, including gender, T category, subglottic extension, as well as tumor bulk, were also prognostically important for local control. CONCLUSIONS: This analysis, in a large number of similarly treated patients, indicates that pretreatment Hb is an independent prognostic factor for local control in patients with T1/T2 carcinoma of the glottis treated with RT. The underlying biology of this observation needs to be explored, and using this information, it may be possible to develop strategies to improve treatment outcome.

Carcinoma, Squamous Cell↗
PubMed1998

The action of three antiseptics/disinfectants against enveloped and non-enveloped viruses.

The antiviral action of chloroxylenol, benzalkonium chloride and cetrimide/chlorhexidine was assessed against a range of enveloped and non-enveloped human viruses using a suspension test method. Viral suspensions of 10(6)-10(7) pfu/TCID50 or sfu were prepared in each of the antiseptic/disinfectant solutions in the presence of a bovine serum/yeast extract mixture to simulate 'dirty conditions'. During incubation, aliquots were removed at predetermined timepoints up to 10 min to assess the kinetics of inactivation. Results indicate that all products were effective in inactivating the enveloped viruses herpes simplex virus type 1 and human immunodeficiency virus type 1, whilst being ineffective in inactivating human coronavirus, also enveloped, and the non-enveloped viruses. The exception to this was the benzalkonium chloride-based product (Dettol Hospital Concentrate) which was active against the non-enveloped human coxsackie virus. Four antiseptic/disinfectant solutions with chloroxylenol, benzalkonium chloride, cetrimide/chlorhexidine and povidone-iodine were also assessed for antiviral effect against human immunodeficiency virus in the presence of whole human blood. All four solutions proved to be effective within 1 min despite the cytotoxic nature of the compounds to the detection system.

Anti-Infective Agents, Local↗
PubMed1998

Randomized study of chemotherapy and surgery versus radiotherapy for stage IIIA non-small-cell lung cancer: a National Cancer Institute of Canada Clinical Trials Group Study.

Thirty-one patients with stage IIIA (N2) non-small-cell lung cancer were randomized to receive radiotherapy alone or chemotherapy with cisplatin and vinblastine followed by surgery. Response rates to induction chemotherapy and radiotherapy were 50% and 53.3% respectively. Complete surgical resection was possible for 62.5% of patients. Median survival times were 16.2 and 18.7 months for radiotherapy alone and chemotherapy-surgery respectively (P = Ns), with no long-term improvement in survival seen with combined-modality treatment.

Adult↗
PubMed1998

Sensitive ELISA dipstick test for the detection of chloroquine in urine under field conditions.

OBJECTIVE: To evaluate a new enzyme-linked immunosorbent assay (ELISA) dipstick test for detecting chloroquine (CQ) in urine in a malaria-endemic region of north-western Namibia. METHOD: Urine samples from 92 patients attending the outpatient department of Kamhaku Hospital with suspected malaria infection were tested for CQ with both the Dill-Glazko test and the ELISA dipstick test. Results were compared to the history of CQ intake as documented in the patients' health passes. RESULTS: The dipstick test proved an easy-to-handle and very sensitive tool for the detection of CQ with a lower limit of detection at 120 nmol/l. It showed high agreement with the history of CQ intake within the last 6 months. The specificity in a negative control group was 100%. The Dill-Glazko test was far less sensitive and specific with a lower detection limit of 150 micromol/l. CONCLUSION: The dipstick test can be used in pharmacological studies to evaluate the use of CQ, and as an inclusion criterion for in vivo and in vitro sensitivity tests, whereas the Dill-Glazko test is appropriate to test compliance during and a few days after CQ intake.

Adolescent↗
PubMed1998

Fertilization failures and abnormal fertilization after intracytoplasmic sperm injection.

This study addresses the incidence of failed (0%) and suboptimal (<50%) fertilization after intracytoplasmic sperm injection (ICSI), variation in the ICSI fertilization rate for specific couples, and the causes of fertilization failure and abnormal fertilization after ICSI. Failed fertilization occurred in only 37 of 1343 cycles (3%). The risk of failure was highest (37%) when only one oocyte was injected, and was lowest (0.8%) when five or more oocytes were collected. The incidence of suboptimal fertilization and the variation in the fertilization rate were studied in 87 couples who each had three cycles of ICSI in which four oocytes were injected with ejaculated spermatozoa. Approximately 74% of these couples achieved >50% fertilization in every cycle. Only 26% of the couples had <50% fertilization in one or more cycles, and most of these (17%) had only a single cycle with suboptimal fertilization. Only four of the 87 couples (5%) had suboptimal fertilization in all three cycles. The difference between the maximum and minimum fertilization rate for a couple was used as an index of variation of the fertilization rate. It was found that 47 couples (54%) had 0-25% variation, 33 couples (38%) had 26-50% fertilization and only seven couples (8%) had >50% variation. The causes of failed and abnormal fertilization were studied in unfertilized and abnormally fertilized oocytes after staining with Hoechst 33342. In total, 1005 unfertilized oocytes were studied, of which 828 (82%) were still at metaphase II and 177 (18%) were activated. Most of the oocytes (83%) contained a spermatozoon and, in the majority of these oocytes, the sperm head was partially or completely decondensed. Hence, failure of oocyte activation was the principal cause of fertilization failure. A similar pattern was observed in activated, unfertilized oocytes, although there was a higher incidence of intact spermatozoa in these oocytes compared with metaphase II, unfertilized oocytes. Interestingly, 56% of the activated oocytes contained a decondensed sperm head which was not processed into a male pronucleus. A total of 169 abnormally fertilized oocytes was also studied. Two anomalies were found: digyny due to retention of the second polar body and its subsequent transformation into a third pronucleus, and abnormal pronuclear size and number.

Adult↗
PubMed1998

The pH 6 antigen of Yersinia pestis binds to beta1-linked galactosyl residues in glycosphingolipids.

The Yersinia pestis pH 6 antigen was expressed by, and purified from, Escherichia coli containing cloned psa genes. By an enzyme-linked immunosorbence-based assay, purified pH 6 antigen bound to gangliotetraosylceramide (GM1A), gangliotriaosylceramide (GM2A), and lactosylceramide (LC) (designations follow the nomenclature of L. Svennerholm [J. Neurochem. 10:613-623, 1963]). Binding to GM1A, GM2A, and LC was saturable, with 50% maximal binding occurring at 498 +/- 4, 390, and 196 +/- 3 nM, respectively. Thin-layer chromatography (TLC) overlay binding confirmed that purified pH 6 antigen bound to GM1A, GM2A, and LC and also revealed binding to hydroxylated galactosylceramide. Intact E. coli cells which expressed the pH 6 antigen had a specificity similar to that of purified pH 6 in the TLC overlay assay except that nonhydroxylated galactosylceramide was also bound. The binding patterns observed indicate that the presence of beta1-linked galactosyl residues in glycosphingolipids is the minimum determinant required for binding of the pH 6 antigen.

Antigens, Bacterial↗
PubMed1998

Preconditioning and adenosine in I/R-induced leukocyte-endothelial cell interactions.

Recently, it was reported that preconditioning reduced leukocyte adhesion following ischemia-reperfusion (I/R). We further examined the effects of preconditioning and adenosine not only on neutrophil adhesion but also on neutrophil rolling and vascular dysfunction. Intravital microscopy revealed a decrease in neutrophil rolling velocity; a profound increase in neutrophil rolling, adhesion, and microvascular dysfunction; and a reduction in venular shear rates associated with 60 min ischemia and 60 min reperfusion in the feline mesentery. Preconditioning (5 min ischemia/10 min reperfusion) prevented subsequent I/R-induced slow neutrophil rolling, neutrophil adhesion, and microvascular dysfunction but did not affect the flux of rolling neutrophils. Adenosine deaminase A1 and A2 adenosine-receptor antagonists had only minor effects on the preconditioning responses. Pretreatment of vessels with exogenous adenosine reduced neutrophil adhesion and microvascular permeability and improved neutrophil rolling velocity and shear forces associated with I/R, but the flux of rolling neutrophils was not affected. Finally, in vitro experiments revealed that adenosine had absolutely no direct effect on neutrophil-endothelial cell interactions. In conclusion, our data suggest that adenosine plays only a minor role in preconditioned vessels and that adenosine per se may not directly affect neutrophil-endothelial cell interactions.

Adenosine↗
PubMed1998

Requesting organ donation: an interview study of donor and nondonor families.

BACKGROUND: Approximately half of the families asked to consider donation of a relative's organs decline to give consent. Understanding the difference between stated public support of organ donation and actual behavior is key to decreasing the shortage of donor organs. OBJECTIVES: To gain insight into the experiences of potential donor families and to define features of the donation-request process and other factors that are associated with consent for organ donation. METHODS: A structured telephone interview was conducted with the immediate next of kin of 164 medically suitable potential organ donors. Interviews 30 to 60 minutes long were held with members of both donor and nondonor families 4 to 6 months after the death of the study participant's relative. RESULTS: Several factors were associated with consent for organ donation: characteristics of the patient and the patient's family, beliefs and attitudes about organ donation and transplantation, whether the family knew the deceased's wishes about donation, the family's satisfaction with the hospital care that their relative received, specific aspects of the donation-request process, and the family's understanding of brain death. CONCLUSIONS: Organ donation rates could be increased by enhancing the quality of hospital care and ensuring that the request for donation is handled in a way that meets the families' informational and emotional needs.

Adolescent↗
PubMed1998

Pulmonary lymphomatoid granulomatosis in acquired immunodeficiency syndrome: lesions with Epstein-Barr virus infection.

We report the clinicopathologic characteristics of pulmonary lymphomatoid granulomatosis (LYG) in 11 patients (identified from a series of 330 consecutive patients who underwent autopsy between 1984 and 1995 at the University of Texas Medical Branch at Galveston, Texas) with a diagnosis of acquired immunodeficiency syndrome (AIDS). We used immunohistochemical stains, RNA in situ hybridization (ISH), and gene rearrangement studies to identify the immunophenotype and the presence or absence of Epstein-Barr virus (EBV) infection. All of the patients were men ranging in age from 27 to 65 years (mean age, 38.6 yr). Autopsy lungs of 21 age-matched controls were examined for EBV using ISH; these included 9 patients with AIDS who did not have pulmonary lesions and 12 HIV-negative individuals who died accidentally (mean age, 38.6 yr). All of the 11 pulmonary lesions showed the gross and microscopic characteristics of LYG, with zonal necrosis and prominent angioinvasion. The tumor nodules consisted of a mixture of atypical large lymphocytes, with vesicular nuclei and prominent nucleoli and with a background of small and intermediate-size lymphocytes, histiocytes, and plasma cells. The large lymphocytes were CD20 positive, consistent with a B-cell phenotype. Ten of the 11 cases demonstrated EBV1-encoded RNA and CD20 positivity in the large, atypical lymphocytes by double labeling. One patient showed EBV positivity in CD20-negative, CD45RO-positive large cells, but these cells were CD3 negative and showed a monoclonal heavy chain gene rearrangement by polymerase chain reaction, indicating that these were of B-cell origin. Aberrant CD43 coexpression was identified in four cases. EBV latent membrane protein was demonstrated in 9 of 11 cases by immunohistochemical stains. The lungs of all of the 21 control patients were negative for EBV by ISH. We conclude that, in our series, AIDS-associated LYG is a B-cell neoplasm and that it has a strong association with EBV infection.

Adult↗