Allogeneic BMT and patient eligibility based on psychosocial criteria: a survey of BMT professionals.

BMT professionals were compared regarding their willingness to proceed with allogeneic BMT given select psychosocial issues. A questionnaire was sent to 660 physician members of ASBMT, 92 social work members of BMT Special Interest Group, Association of Oncology Social Work, and 626 nurse members of BMT Special Interest Group, Oncology Nursing Society; 597 responded with a response rate of 43.5%. Items included background information, followed by 17 case vignettes; each represented a different psychosocial issue to which respondents indicated whether or not they would recommend proceeding with allogeneic BMT. In every vignette, at least 10% of respondents indicated they would not proceed. In six vignettes, at least 64% indicated do not proceed: suicidal ideation (86.8%), uses addictive illicit drugs (81.7%), history of noncompliance (80.5%), no lay caregiver (69.3%), alcoholic (64.8%), and mild dementia/Alzheimer's (64.4%). In 10 vignettes, at least 73% indicated proceed. On four vignettes, professional subgroups differed in their recommendation on whether or not to proceed with allogeneic BMT. Qualitative data suggest that this decision is contingent on the perceived acuity, severity, and currency of the psychosocial issue, patient ability to comply with treatment given the issue, and its manageability as a risk factor for treatment related vulnerability and outcomes.

Prognostic significance of pre-transplant quality of life in allogeneic hematopoietic cell transplantation recipients.

Quality of life (QOL) is an important outcome for hematopoietic cell transplantation (HCT) recipients. Whether pre-HCT QOL adds prognostic information to patient and disease related risk factors has not been well described. We investigated the association of pre-HCT QOL with relapse, non-relapse mortality (NRM), and overall mortality after allogeneic HCT. From 2003 to 2012, the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale instrument was administered before transplantation to 409 first allogeneic HCT recipients. We examined the association of the three outcomes with (1) individual QOL domains, (2) trial outcome index (TOI) and (3) total score. In multivariable models with individual domains, functional well-being (hazard ratio (HR) 0.95, P=0.025) and additional concerns (HR 1.39, P=0.002) were associated with reduced risk of relapse, no domain was associated with NRM, and better physical well-being was associated with reduced risk of overall mortality (HR 0.97, P=0.04). TOI was not associated with relapse or NRM but was associated with reduced risk of overall mortality (HR 0.93, P=0.05). Total score was not associated with any of the three outcomes. HCT-comorbidity index score was prognostic for greater risk of relapse and mortality but not NRM. QOL assessments, particularly physical functioning and functional well-being, may provide independent prognostic information beyond standard clinical measures in allogeneic HCT recipients.

Endothelin-mediated constriction of prenodal lymphatic vessels in the canine forelimb.

Endothelin is a 21 amino acid peptide which is produced by the vascular endothelium and is believed to be the mediator of endothelium-dependent vasoconstriction. In the current study we assessed the ability of synthetic human endothelin-1 to affect prenodal lymphatic vessel contractility in the canine forelimb. Intralymphatic infusion of endothelin at 1.09 x 10(-9), 1.09 x 10(-8) and 1.09 x 10(-7) M significantly constricted lymphatic vessels as evidenced by dose-dependent increases in lymphatic perfusion pressure. The increase in lymphatic perfusion pressure seen during intralymphatic infusion of endothelin at 1.09 x 10(-8) M during the intra-arterial infusion of phentolamine was not significantly different from that seen prior to phentolamine, indicating that endothelin-mediated lymphatic constriction is not alpha-receptor mediated. Intra-arterial infusion of endothelin at three infusion rates significantly increased forelimb arterial, systemic and lymphatic perfusion pressures. The constriction seen when endothelin (1.09 x 10(-8) M) was infused intralymphatically in the intact lymphatic system was not significantly different from that observed when only the prenodal lymph vessel was perfused. This indicated that the lymph nodes and efferent lymph vessels do not contribute significantly to the lymphatic constriction produced by endothelin. These data are consistent with the hypothesis that endothelin may modulate lymphatic function under either normal or pathophysiological conditions.

Relationship between substance P, intestinal wall compliance and vascular resistance in the canine ileum.

Substance P (SP) is one of many vasoactive peptides found within the gastrointestinal tract with actions on intestinal smooth muscle. Thus, its vasodilatory action could be attenuated through its stimulatory effect on intestinal smooth muscle producing subsequent elevations in extravascular pressure and thus, passively opposing the vasodilation. The aim of this study was to examine for such a possibility for SP by simultaneously assessing ileal perfusion pressure and intestinal wall compliance in the canine ileum during intra-arterial infusion of SP. Infusion of SP at either 0.74 or 7.4 pmol/min significantly decreased ileal perfusion pressure by 8 and 30%, respectively, without affecting wall compliance. During SP infusion at 74 pmol/min, perfusion pressure fell by 49% while wall compliance decreased by 43%, reflecting a significant increase in ileal wall tension. During SP infusion at 7.4 and 74 pmol/min, a 'two-phase' reduction in perfusion pressure was observed. These data suggest that although SP markedly increases ileal wall tension, the elevation in extravascular pressure produced is not strong enough to overcome its potent vasodilatory action in the canine ileum. The potential of a physiologic role for blood-borne SP is discussed.

On-site screening for urinary Hg concentrations and correlation with glomerular and renal tubular function.

At the American Dental Association 1985 and 1986 Annual Sessions, an on-site screening for mercury was conducted as part of the Health Screening Program (HSP) to identify dentists having elevated urinary mercury concentrations. The data generated from this study were used to examine the relationship between elevated urinary mercury exposure and kidney dysfunction. Kidney dysfunction was assessed by measurement of serum and urine beta 2 microglobulin concentrations, serum creatinine, and creatinine clearance. The mean values found for urinary mercury were 5.8 micrograms Hg/L and 7.6 micrograms Hg/L for 1985 and 1986, respectively. Urinary mercury concentrations for this population were found to fall within the range of not detected to 115 micrograms Hg/L. Of the total number of participants assayed in 1985 and 1986, roughly 10 percent of the sample exhibited elevated mercury concentrations above 20 micrograms Hg/L. An analysis of the clinical markers indicated no clear relationship between elevated urinary mercury concentrations and kidney dysfunction. In addition to mercury testing, all dentists who participated in the 1985 and 1986 HSP were issued a questionnaire soliciting information as to their professional exposure. Those participants who were identified as having elevated urinary mercury concentrations in the 1985 HSP were issued a followup questionnaire that addressed psychological and neuropsychological symptoms. From these questionnaires three significant relationships were found. These relationships were associated with mercury/amalgam handling and skin contact, the number of amalgams placed by the dentist, and the number of hours of practice per week. The reported absence of a clear relationship between urinary mercury concentrations and potential kidney dysfunction is in agreement with other findings at the mercury concentrations tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Vascular responses in the equine digit.

The digital circulation was isolated in 12 ponies under pentobarbital anesthesia. Blood flow was either controlled by a pump or measured under natural perfusion. The responses to rapid changes and stoppages of blood flow indicated no evidence of autoregulation or reactive hyperemia. Local administration of acetylcholine, histamine, and prostaglandins E1 and E2 decreased prevenous resistance, whereas epinephrine and serotonin caused prevenous constriction. Large doses of epinephrine and serotonin decreased venous caliber. The effects of prostaglandins A1 and F2alpha were variable. The equine digital vasculature responds to changes in flow and to vasoactive agents like the canine forelimb skin vasculature.

Digital vascular responses and permeability in equine alimentary laminitis.

Digital vascular pressures, blood flow, and vascular resistances were measured in 11 control ponies and in 8 animals (7 ponies and 1 horse) affected with laminitis created by feeding a high starch ration. Animals with laminitis had increased digital blood flow, increased arterial, small vein, and large vein pressures, and decreased vascular resistances. Comparison of digital lymph flow rates and protein concentrations in animals with laminitis and control animals revealed no differences. Digital vascular responses of the 2 groups to acetylcholine, epinephrine, histamine, or serotonin also did not differ. Thus, the increased digital blood flow observed in animals with laminitis could not be attributed to altered responsivenss to the previously mentioned vasoactive agents. The studies also provided no evidence for increased capillary permeability in digits of animals affected with laminitis.

Quality of life and outcomes in patients⩾60 years of age after allogeneic hematopoietic cell transplantation.

Hematopoietic cell transplantation (HCT) has become an established standard of care for many older patients with hematologic malignancies. The effect of transplantation on the quality of life (QOL) of older patients, however, has not been well studied. We thus analyzed QOL in patients ⩾60 undergoing an allogeneic HCT compared with patients <60 years. Prospective psychometric instruments were administered to 351 patients who underwent HCT from 2003 to 2010. Psychometric data were assessed longitudinally by validated questionnaires: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), Coping Inventory and the Profile of Mood State-Short Form. Patients ⩾60 reported better social (P=0.006) and functional well-being (P=0.05) with FACT assessment, and had better total scores, (P=0.043) across all time points. When adjusted for baseline QOL scores as a covariate, social well-being remained significantly better, whereas the other scores became non-significant. With a median follow-up of 49 months, there were no significant differences in OS, relapse-free survival, relapse or chronic GVHD. This study provides further evidence that advanced age should not be a barrier in the decision to pursue allogeneic HCT. Older patients achieved comparable QOL when compared with younger patients.

Validating the positive impact of in-hospital lay care-partner support on patient survival in allogeneic BMT: a prospective study.

This prospective study validates the finding from retrospective research that having an inpatient lay care-partner (CP) is associated with better survival following allogeneic BMT. Compared with patients without a CP (n=76), patients with a CP (n=88) have significantly better OS (P=0.017) and relapse-free survival (RFS) (P=0.020). Four-year and median survivals were 42% and 36 months among patients with CPs, compared with 26% and 10 months among those without CPs. Four-year survival and median RFS were 39% and 25 months among those with CPs, compared with 23% and 7 months among those without CPs. Further, better survival and RFS were associated with CP visit duration of >3 h per day (P=0.005 and P=0.007, respectively) and with CP frequency of visits >75% of inpatient days (P=0.004 and P=0.010, respectively). A CP support program should encourage not only presence of a CP but also duration and frequency of CP visits associated with better patient survival.

Utility of the psychosocial assessment of candidates for transplantation (PACT) scale in allogeneic BMT.

The psychosocial assessment of candidates for transplantation (PACT) scale was completed before the transplant on 120 patients who underwent allogeneic transplant from November 2003 to June 2007. The PACT has eight subscales, each rated on a 5-point scale, and an initial and final rating independently based on the rater's overall impressions of the candidate's acceptability for transplant. This exploratory study assessed the clinical utility of the PACT scale for psychosocial screening in allogeneic BMT. Associations of the PACT subscales and the final rating with sixteen post transplant medical outcomes were examined using the Jonchkheere-Terpstra test, the Cochran-Armitage test or the Cox proportional hazards analysis. Significant relationships (P

Constriction of canine prenodal lymphatic vessels following the intra-arterial injection of vasoactive agents and hemorrhage.

In the forelimbs of anesthetized dogs, perfused at constant arterial inflow, we measured the pressure in a prenodal lymphatic vessel before and following arterial hemorrhage to a mean systemic arterial pressure of approximately 55 mmHg. We also made bolus intra-arterial injections of 1 microgram epinephrine and arginine vasopressin or 20 micrograms dopamine, prostaglandin F2 alpha and tyramine. Hemorrhage and all vasoactive substances significantly increased forelimb perfusion pressure and skin small artery pressure. Skin small vein pressure was significantly decreased by hemorrhage or injection of epinephrine, dopamine or tyramine, but was not significantly altered by arginine vasopressin or prostaglandin F2 alpha. Mean systemic arterial pressure was decreased by hemorrhage, increased by arginine vasopressin, tyramine and prostaglandin F2 alpha but remained unchanged following the injection of either epinephrine or dopamine. Lymphatic pressure was significantly increased following hemorrhage or the injection of all vasoactive agents. The increase seen with tyramine was small but consistent and thus statistically significant. These data indicate that the prenodal lymphatic vessels of the canine forelimb actively constrict in response to the neural and/or hormonal consequences of arterial hemorrhage or the introduction of exogenous vasoactive substances into the arterial blood supply to the forelimb. The results of the current study support the possibility that lymphatic function, through activation of lymphatic smooth muscle, is subject to neural and/or hormonal regulation in certain physiological and/or pathophysiological states.

Neurokinin A and B: potent vasodilators in the canine forelimb.

Neurokinin A and neurokinin B may play a role in control of the peripheral circulation in either physiological or pathophysiological conditions. We have infused these peptides intra-arterially at three infusion rates each to assess their actions on vascular pressures, blood flows and total and segmental resistances in skin and skeletal muscle in the canine forelimb. Neurokinin A infusions (.01, .1, and 1 micrograms/min) decreased total forelimb resistance; transiently, 26% and 57%, respectively. The decrease in resistance was equally distributed between the skin and skeletal muscle circulations and was manifest in both large artery and small vessel resistances. Systemic and forelimb arterial pressures were decreased in a dose-dependent manner. Neurokinin B infusions (.5, 1 and 5 micrograms/min) decreased total forelimb resistance 29%, 31%, and 52%, respectively. The decrease in resistance was equally distributed between the skin and skeletal muscle circulations and was the result of decreases in both large artery and small vessel resistances. Systemic and forelimb arterial pressures were decreased in a dose-dependent manner. The potent effect of neurokinins on vascular resistance and their concentration in perivascular nerves innervating the resistance vessels of the circulation suggests a potential role for these neuropeptides in circulatory control.

Constriction of perfused lymphatics by acetylcholine, bradykinin and histamine.

We have previously reported that perfused lymphatic vessels in the canine forelimb constrict in response to increased sympathetic nerve activity or local infusions of endogenous vasoconstrictor substances. In the present study we have assessed the effects of three endogenous vasodilators; acetylcholine, bradykinin and histamine on lymphatic vessel contractility. Each one of these agents, when infused intralymphatically, produced lymphatic constriction as evidenced by significant increases in lymphatic perfusion pressure. The threshold concentrations which produced lymphatic constriction were between 10(-6) and 10(-5) molar for acetylcholine and bradykinin and between 10(-5) and 10(-4) molar for histamine. Surgical exclusion of the lymph nodes and efferent lymph vessels from the perfused tissue did not significantly affect the observed response, indicating that the response occurs predominately in the prenodal segments of the lymphatic system. Infusion of acetylcholine and bradykinin into the arterial supply to the forelimb did not significantly alter lymphatic perfusion pressure, unlike the response seen when catecholamines are infused intra-arterially. Histamine displayed an unusual property in that it constricts lymph vessels upon initial administration but was thereafter completely ineffective. Constriction of lymphatic vessels by substances which are potent vasodilators clearly indicates that significant functional differences exist in endothelial cell/smooth muscle relationships between blood vessels and lymph vessels.

The inflammatory actions of platelet activating factor are blocked by levorotatory terbutaline.

Platelet activating factor (PAF), a potent vasoactive lipid, may play an important role in the inflammatory process. In this study, we infused PAF intra-arterially to characterize its edematogenic potency in the canine forelimb. We have also assessed the ability of the beta 2-receptor agonist l-terbutaline to block PAF-mediated edema formation. The infusion of PAF at .25 micrograms/min, .5 micrograms/min and 1 micrograms/min increased forelimb arterial pressures and, at the two higher dosages, significantly decreased systemic arterial pressure. PAF infusions increased transvascular fluid and macromolecular flux as indicated by significant increases in skin lymph flow, protein concentration and protein transport. The intra-arterial infusion of l-terbutaline at 1 micrograms/min significantly decreased forelimb arterial pressures but did not affect small vein pressure, systemic pressure or forelimb lymph parameters. The subsequent infusion of PAF at .5 micrograms/min, during the continued infusion of l-terbutaline, failed to significantly affect forelimb lymph parameters. These data indicate that PAF is significantly more potent as an edematogenic agent in the forelimb than histamine or bradykinin. Furthermore, the blockade of PAF-mediated edema formation by l-terbutaline suggests that beta 2-receptor agonists may be capable of antagonizing the inflammatory actions of a wide variety of putative inflammatory mediators.

Evidence for constriction of canine prenodal lymphatic vessels by vasoactive agents and carotid occlusion.

We measured pressure in a prenodal lymphatic in the canine forelimb during constant flow pump-perfusion of the brachial artery. We made bolus i.a. injections of 1.0 micrograms angiotensin II, norepinephrine, bombesin, or bradykinin, 20 micrograms 5-hydroxytryptamine (5HT), or occluded the carotid arteries. Norepinephrine, 5HT, or carotid occlusion produced regular rises in forelimb perfusion pressure and in lymphatic pressure. Angiotensin II increased forelimb arterial pressures but increased lymphatic pressure in only four experiments. Bombesin increased artery pressures but did not affect lymphatic pressure. Small vein pressure was increased by carotid occlusion, 5HT and norepinephrine. Increases in lymphatic pressure were coincident with increases in vein pressure but no related in magnitude. Bradykinin decreased forelimb arterial and venous pressures but did not affect lymphatic pressure. Either active constriction of lymphatic vessels or passive compression by movements of adjacent blood vessels could increase lymphatic pressure. These data do not preclude a passive component of pressure rise in the lymphatics nor do they support the concept. We conclude that active constriction of prenodal lymphatic vessels in the dog forelimb can occur in response to circulating vasoactive agents and bilateral carotid occlusion.

Effects of bolus injections of leukotrienes and norepinephrine on forelimb vascular and lymphatic pressures.

Leukotrienes, lypoxygenase metabolites of arachadonic acid, have been reported to be potent vasoconstrictors in some organs. This study was undertaken to delineate the actions of leukotrienes on both vascular and lymphatic vessels in the canine forelimb. Bolus intra-arterial injections of 1 microgram and 10 micrograms of leukotriene B4, C4, and D4 and 1 microgram of norepinephrine were made into forelimbs perfused at constant flow. Norepinephrine significantly increased systemic, forelimb perfusion and small artery pressures. Lymphatic pressure was significantly increased from a control of 6.6 mmHg to a peak of 14.4 mmHg. Leukotriene B4 in either dosage, did not significantly affect vascular or lymphatic pressures. Leukotriene C4 (1 microgram or 10 micrograms) significantly increased systemic and forelimb arterial pressures but did not alter lymphatic pressure. Leukotriene D4 (1 microgram) significantly increased small artery pressure. Leukotriene D4 (10 micrograms) increased systemic and forelimb arterial pressures. Neither dosage of leukotriene D4 significantly affected lymphatic pressure. Repeat injection of norepinephrine after completion of all leukotriene injections again markedly increased systemic, forelimb arterial and lymphatic pressures. These data indicate that leukotrienes exhibit only mild constrictor effects on forelimb blood vessels and do not significantly affect forelimb prenodal lymphatic vessels.

O-(beta-hydroxyethyl)-rutoside (Venoruton) fails to block histamine or bradykinin-induced edema formation in the canine forelimb perfused at constant arterial inflow.

O-(beta-hydroxyethyl)-rutoside (Venoruton) has been reported to alleviate edema formation in chronic venous insufficiency. In an attempt to elucidate Venoruton's potential as an antiinflammatory agent, we infused Venoruton (20 mg/minute) intraarterially into the canine forelimb perfused at constant flow during the simultaneous intraarterial infusion of histamine (4 micrograms base/minute) or bradykinin (2 micrograms/minute). The infusion of Venoruton alone for forty minutes resulted in a small but significant increase in forelimb arterial pressures but no change in systemic pressure or forelimb skin lymph flow, protein concentration or protein transport. Subsequent infusion of either histamine or bradykinin resulted in a significant decrease in forelimb arterial pressures and a marked increase in skin lymph flow, lymph total protein concentration and lymph total protein transport. The changes in forelimb vascular pressures and skin lymph parameters were similar to those seen during the infusion of either histamine or bradykinin alone. These data indicate that the intraarterial infusion of Venoruton at this dosage does not inhibit the ability of simultaneously infused histamine or bradykinin to increase transvascular fluid and macromolecular efflux in the canine forelimb perfused at constant arterial inflow.