Biomedical subjects

A Yeager

Publications and source records attributed to A Yeager.

At least 19 recordsLinked to original sources

PubMed2004

The rationale behind autologous autoimmune hematopoietic stem cell transplant conditioning regimens: concerns over the use of total-body irradiation in systemic sclerosis.

Hematopoietic stem cell transplantation (HSCT) is becoming an increasingly recognized indication for treatment of autoimmune diseases and severe immune-mediated disorders. However, multicenter registry data have demonstrated higher than anticipated early toxicity, approximately 10% for autoimmune diseases in general, and 20-27% for diffuse systemic sclerosis (scleroderma). If uncorrected, this high treatment-related mortality will hinder development of stem cell therapy for immune-mediated diseases. In order to develop safer regimens, we address some pitfalls and concepts involved in design and selection of conditioning regimens for autoimmune diseases in general, and because it is associated with the highest regimen-related toxicity, scleroderma in specific.

Autoimmune Diseases↗

PubMed2000

Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia.

PURPOSE: Preparative regimens involving total-body irradiation (TBI) produce significant late toxicities in some children who receive bone marrow transplants, including impaired growth and intellectual development. Busulfan is often used as an alternative to TBI, but there are few data regarding its relative efficacy. PATIENTS AND METHODS: We compared outcomes of HLA-identical sibling transplants for acute lymphoblastic leukemia (ALL) in children (< 20 years of age) who received cyclophosphamide plus TBI (CY/TBI) (n = 451) versus those who received busulfan plus cyclophosphamide (Bu/CY) (n = 176) for pretransplant conditioning. Patients received transplants between 1988 and 1995 and their results were reported to the International Bone Marrow Transplant Registry by 144 participating institutions. The CY/TBI and Bu/CY groups did not differ in gender, immune phenotype, leukocyte count at the time of diagnosis, chromosome abnormalities, remission status, or length of initial remission. T-cell depletion was used more frequently in the CY/TBI group; the Bu/CY group included a higher proportion of children who were less than 5 years of age. The median follow-up period was 37 months. RESULTS: The 3-year probabilities of survival were 55% (95% confidence interval [CI], 50% to 60%) with TBI/CY and 40% (95% CI, 32% to 48%) with Bu/CY (univariate P =.003). The 3-year probabilities of leukemia-free survival were 50% (95% CI, 45% to 55%) and 35% (95% CI, 28% to 43%), respectively (univariate P =.005). In a multivariate analysis, the risks of relapse were similar in the two groups (relative risk [RR], 1.30 for Bu/CY v CY/TBI; P =.1). Treatment-related mortality was higher in the Bu/CY group (RR, 1.68; P =.012). Death and treatment failure (relapse or death, inverse of leukemia-free survival) were more frequent in the Bu/CY group (RR, 1. 39; P =.017 for death; RR, 1.42; P =.006 for treatment failure). CONCLUSION: These data indicate superior survival with CY/TBI conditioning, compared with Bu/CY conditioning, for HLA-identical sibling bone marrow transplants in children with ALL.

Adolescent↗

PubMed1999

Car surfing: an uncommon cause of traumatic injury.

Car surfing is an infrequent cause of traumatic injuries treated by emergency physicians. This very dangerous activity can result in serious injury or death. We report 5 cases of injuries caused by car surfing seen at our hospital during 1996 and 1997. All involved head injuries after a fall from a moving motor vehicle. There were 3 male and 2 female patients, and 3 cases were fatal. Health care providers should be aware of this type of injury and support efforts to prevent it.

Accidents, Traffic↗

PubMed1998

An open-label dose comparison study of ondansetron for the prevention of emesis associated with chemotherapy prior to bone marrow transplantation.

Nausea and vomiting are significant side effects in bone marrow transplant (BMT) patients who receive high-dose preparative regimens. Higher than conventional ondansetron doses and continuous infusion might improve emetic control, because of the high doses and combinations of chemotherapy (CT) used in this setting. Our objective was to conduct a prospective, randomized study comparing two different administration methods of high-dose ondansetron during a BMT preparative regimen in breast cancer patients. Patients were eligible if they were nonpregnant women over 18 but under 65 years of age, undergoing highly emetogenic CT in preparation for autologous BMT. All patients received ondansetron as an intermittent (INT = 24 mg i.v. q 12 h/day) or continuous intravenous infusion (CIV = 8 mg i.v. loading dose followed by a continuous infusion of 2 mg/h per day). A total of 66 patients were enrolled in the study (n = 34, INT; n = 32, CIV). There was no statistical difference between treatment groups in the worst grade of emesis for the entire study period (P = 0.49). Greater than 90% of all patients were graded as failures (> or = 5 emetic episodes or need for rescue antiemetics). Complete control (no vomiting episodes) and complete plus major control (1-2 emetic episodes) per day ranged from 8% to 85% and 11% to 91%, respectively. There was no significant difference between the treatment arms in: grade of emesis, episodes of vomiting and retching, nausea scores, and mean number of rescue medications administered. There were no differences in efficacy when high-dose ondansetron was given as CIV or INT for the control of nausea and vomiting in breast cancer patients undergoing high-dose CT for autologous BMT. Ondansetron alone was not adequate to provide sustained control of CT-induced nausea and vomiting over the entire 5-day study period. A combination of antiemetics targeting various mechanisms of CT-induced nausea and vomiting may be necessary to improve response rates.

Adult↗

PubMed1998

Calcipotriol toxicity in a dog.

A six-month-old Labrador retriever was presented for investigation of acute polyuria, polydipsia and haematemesis six hours following ingestion of a tube of the topical antipsoriatic vitamin D analogue, calcipotriol. Transient hypercalcaemia, azotaemia, proteinuria, thrombocytopenia and ventricular arrhythmias ensued. Abdominal ultrasonography and echocardiography revealed evidence of diffuse soft tissue mineralisation. Despite 13 days of intensive supportive care, the dog was euthanased due to continued haematemesis and anorexia. Necropsy confirmed mineralisation and necrosis of multiple organ systems consistent with vitamin D toxicity.

Animals↗

PubMed1997

Collaborative multicenter investigation of marrow transplantation for sickle cell disease: current results and future directions.

We present updated results of a multicenter collaborative investigation of bone marrow transplantation for sickle cell disease. Between September 1991 and April 1997, thirty-four children less than 16 years of age with severe sickle cell disease received marrow allografts from HLA-identical siblings. Indications for transplantation included a history of stroke (n = 17), recurrent acute chest syndrome or sickle pulmonary disease (n = 10), and recurrent vaso-occlusive crises (n = 7). Twenty-one patients received regular red blood cell (RBC) transfusions to prevent complications of sickle cell disease. Patients were prepared for transplantation with busulfan, cyclophosphamide, and antithymocyte globulin or CAMPATH (Cambridge Pathology) antibody. Thirty-two of the 34 patients survived, with a median follow-up of 26.5 months (range, 0.2-66.9 months); and 28 patients demonstrated stable engraftment of donor hematopoietic cells. Graft rejection or recurrence of sickle cell disease occurred in four patients, and two patients died of intracranial hemorrhage or graft-vs.-host disease. In the group of 34 children with symptoms of advanced sickle cell disease, current Kaplan-Meier estimates of survival and event-free survival are 93% and 79%, respectively.

Adolescent↗

PubMed1995

The relationship of the skin conductance and finger pulse amplitude components of the orienting response to season of birth in schizophrenia and depression.

Schizophrenia is said to be associated with a modest excess of winter births. We examined relations of season of birth (SOB) to the skin conductance response (SCR) and finger pulse amplitude response (FPAR) components of the orienting response (OR) in 83 schizophrenic patients, 59 depressed patients, and 81 normal controls. SCR-OR nonresponding was more prevalent among depressed patients regardless of SOB, whereas only winter-born schizophrenics showed significantly more frequent electrodermal nonresponding than controls. However, this latter relation was not confirmed with log linear analysis. No other relations of SOB to SCR-OR or FPAR-OR nonresponding were significant. Our data do not support the view that nonresponding in the SCR or FPAR components of the OR is associated with winter birth either in schizophrenia or depression.

Adolescent↗

PubMed1995

Differing patterns of electrodermal and finger pulse responsivity in schizophrenia and depression.

Non-response of the autonomic orienting response (OR), as indexed jointly by deficient skin conductance (SCR) and finger pulse amplitude responding (FPAR), has been shown to occur with excessive frequency in the schizophrenic population. The present study is an attempt to replicate earlier evidence that SCR-OR and FPAR-OR, when measured in concert, could distinguish schizophrenic from depressed patients (Bernstein et al. 1988). This issue is critical of the question of diagnostic specificity of OR non-responding, since reduced SCR has been found repeatedly in depression as well as in schizophrenia. We examined SCR and FPAR concurrently in 69 schizophrenic, 45 depressed, and 67 normal subjects. SCR non-responding was more frequent in both schizophrenics and depressives than in normal controls, while only the schizophrenics displayed excessive FPAR non-responding. Moreover, among SCR non-responders, concordant OR non-responding--defined as non-responding indexed simultaneously in both the SCR and FPAR components--was most common in the schizophrenic sample. These findings support our previous conclusion that OR non-responding in depression, may have distinct peripheral origins. Our results also suggest that measuring multiple biochemically distinct components of the OR may be more sound methodologically than obtaining a single channel recording.

Adolescent↗

PubMed1992

Results of nocturnal penile tumescence studies are abnormal in sexually functional diabetic men.

Nocturnal penile tumescence (NPT) studies are commonly used in the assessment of sexual dysfunction in diabetic men. While much of the evidence in favor of its use has come from the observation of markedly abnormal NPT in impotent diabetic men, little research has focused on the quality of nocturnal erections in sexually functional diabetics. Ten diabetic men who reported normal daytime sexual function were studied with 4 nights of polysomnography, including NPT assessment. They had significantly diminished NPT profiles when compared with that of an age-matched, nondiabetic, healthy control group. Without controlling for the effect of diabetes on NPT, between 70% and 90% of sexually functional diabetics had NPT profiles in a range that would be classified as indicative of organic sexual dysfunction for a man presenting for evaluation of sexual dysfunction. The finding of NPT abnormalities in a diabetic man should not be taken as evidence for irreversible sexual dysfunction. Rather, the condition of diabetes appears to result in NPT abnormalities, regardless of the adequacy of daytime sexual function.

Adult↗

PubMed1991

Subtyping DSM-III-R primary insomnia: a literature review by the DSM-IV Work Group on Sleep Disorders.

OBJECTIVE: The authors review the usefulness, reliability, and validity of recently proposed subtypes of primary insomnia. DSM-III uses "primary insomnia" to indicate chronic insomnia not associated with other diagnosable mental or medical disorders, whereas the International Classification of Sleep Disorders (ICSD) recognizes three subtypes: psychophysiological insomnia, idiopathic insomnia, and sleep state misperception. METHOD: After reviewing all of the primary source references for each insomnia disorder in the ICSD and all of the additional primary sources cited in each of these, the authors conducted an automated literature search using Medline. Of the 48 primary sources located, the authors selected 27 studies that were reported in peer-reviewed journals, had the largest available subject groups, used diagnostic reliability procedures, and included control groups. RESULTS: The studies reviewed contained limited empirical support for the proposed distinction between idiopathic and psychophysiological insomnia. Sleep state misperception appears, however, to be a highly prevalent feature of chronic insomnia generally, rather than only a specific disorder per se. CONCLUSIONS: The authors conclude that there is not yet sufficient empirical evidence to warrant the abandonment of DSM-III-R "primary insomnia" and the adoption of the ICSD subtypes in DSM-IV. However, they affirm the heuristic value of the ICSD subtypes and the need for field trials to compare the performance characteristics of the DSM-III-R and ICSD systems with respect to 1) interrater reliability, 2) effects of rater expertise (generalist versus specialist) on rates of agreement, and 3) effects of polysomnographic data on rates of agreement.

Humans↗

PubMed1990

Comparative cytogenetic analysis between cyclophosphamide-sensitive and -resistant lines of acute myeloid leukemia in the Lewis Brown Norway hybrid rat.

An animal model of acute myeloid leukemia (AML) has been developed in the Brown Norway (BN) rat and has successfully been introduced into the Lewis x BN F1 hybrid (LBN) and designated LBN AML. The original LBN AML is sensitive to the chemotherapeutic agent cyclophosphamide (CY). Recently, a CY-resistant cell line of LBN AML has been established. To characterize this animal model of human leukemia better, we analyzed and compared the chromosomal makeup of both the CY-sensitive and CY-resistant LBN AML lines. The CY-sensitive LBN AML cultures contained two cell lines--line I (88%): 41,XX,-1,-2,-9,del(12)(q16), + der(1)t(1;?8)(p13;q31), + der(2)t(2;9)(p11;q11); and line II (12%): 41,XX,-1,-2,-9,del(12),del(20)(q13) + der(1)t(1;?8)(p13;q31), + der(2)t(2;9)(p11;q11). The recently developed CY-resistant AML cells contained two cell lines--line I (88%): 41,XX,-1,-2,-9,del(3)(q36q42.1),del(4) (q42.2),?t(5;?)(q35;?),?t(8;?)(q24;?),del(12)(q16), + der(1)t(1;?8)(p13;q31), + der(2)t(2;9)(p11;q11); and line II (12%): 42,XX (probably represents host contamination). The new chromosomal aberrations in the CY-resistant line I [del(3)(q36q42.1),del(4)(q42.2),?t(5;?)(q35;?), and ?t(8;?)(q24;?)] suggest a possible interrelationship between these secondary karyotypic abnormalities and acquisition of resistance to the chemotherapeutic agent.

Acute Disease↗

PubMed1990

Comparison of ejection fraction and Goldman risk factor analysis to dipyridamole-thallium 201 studies in the evaluation of cardiac morbidity after aortic aneurysm surgery.

Associated coronary artery disease is the critical factor that influences early and late mortality after abdominal aortic aneurysm surgery. Dipyridamole-thallium 201 scintigraphy, left ventricular ejection fraction, and Goldman risk factor analysis have been suggested as preoperative noninvasive screening methods to detect significant coronary artery disease. In this series of 95 elective abdominal aortic aneurysm repairs dipyridamole-thallium 201 scintigraphy was highly predictive of the absence of perioperative cardiac morbidity (96% specificity, 44/46 normal scans, no cardiac morbidity), whereas ejection fraction (73% specificity, 31/42 normal ejection fraction, no cardiac morbidity) and Goldman risk factor analysis (84% specificity, 44/51 class I, no cardiac morbidity) were less. Furthermore, thallium redistribution on dipyridamole-thallium 201 scintigraphy leading to coronary angiography identified a significant number of patients with occult coronary artery disease who required preoperative coronary revascularization (8%, 8/95) and might have remained undetected on the basis of left ventricular ejection fraction or Goldman risk factor analysis. Finally, fixed thallium deficit, which some investigators have interpreted as a low probability finding for cardiac morbidity, was associated with a higher than expected incidence of cardiac complications. Forty-six percent (7/15) of all postoperative cardiac complications (three myocardial infarctions, three ischemic events, one death) occurred in patients with abdominal aortic aneurysms with fixed deficits. This suggests that patients with fixed deficits on dipyridamole-thallium 201 scintigraphy should be considered for later "delayed" (4 hours) thallium images or coronary angiography or both.

Aged↗

PubMed1990

The effects of prolonged stimulus repetition with repeated switching of target status on the orienting response in schizophrenia and depression.

Schizophrenic patients are frequently orienting nonresponders to innocuous stimuli, become responsive to significant target signals, and become hyporesponsive again on prolonged repetition. We wish to a) determine whether schizophrenic patients can display orienting response (OR) flexibility, responding to newly designated targets and ceasing to respond to newly designated nontargets; b) determine whether renewed hyporesponding can be averted with reminders of target relevance and repeated introduction of new targets; and c) compare schizophrenics with depressives and normal controls. Fifty schizophrenics (14 drug free), 50 depressives (20 drug free), and 50 normal controls receive four trial blocks involving the same sequence of 16 1000- or 2000-Hz tones delivered to either the right or left ear. A subsample of each group (N = 14) receives all blocks as a simple habituation series; others (N = 36) have to press a pedal for designated target signals (left ear or right ear, 1000 Hz or 2000 Hz), ignoring all nontarget tones. On each trial block, a new target signal is defined, and previous targets are discarded. Skin conductance and finger pulse amplitude analyses are presented. Both patient groups show enhanced ORs to newly relevant targets and ceased ORs to newly irrelevant former targets as well as normals. Both show OR decline with target repetition despite reminders and new targets.

Acoustic Stimulation↗

PubMed1990

Termination of pregnancy and induction of premature luteolysis by the antiprogestagen, mifepristone, in dogs.

Five pregnant beagle bitches were treated with 2.5 mg mifepristone/kg body weight, twice a day, for 4.5 days starting at Day 32 of gestation. Results of fetal ultrasonography and assay of serum progesterone concentrations every 2-4 days were compared to those in 5 control bitches. Mifepristone resulted in a premature (P less than 0.01) termination of pregnancy (36 +/- 1 vs 65 +/- 1 days), without side effects. The antiprogestagen also caused progesterone to decline to less than 1 ng/ml by Day 40-45 after the preovulatory LH peak (vs 64-67 days in controls) and reduced (P less than 0.05) mean concentrations on Days 34-50 (2.2 +/- 0.5 vs 6.3 +/- 0.3 ng/ml). The results suggest that antiprogestagen therapy is a safe means to terminate unwanted pregnancy in dogs, and that luteal function in pregnant bitches is dependent on luteotrophic support that is blocked by antiprogestagen treatment, directly or indirectly, due to termination of pregnancy.

Abortion, Induced↗

PubMed1990

Density-gradient separation for 4-hydroperoxycyclophosphamide purging of autologous bone marrow grafts.

We studied density-gradient separation of autologous bone marrow grafts in preparation for ex vivo 4-hydroperoxy-cyclophosphamide (4-HC) purging. A two-step procedure of buffy coat isolation followed by Ficoll-diatrizoate separation was used. Buffy-coat cells were isolated primarily either using the COBE 2991 Blood Cell Processor or Haemonetics 30 Cell Separator. All density-gradient separations were performed using the COBE 2991. The nucleated cell recoveries after buffy-coat isolation were 44.3 +/- 10.4% and 85.1 +/- 10.5% (+/- standard deviation, P less than 0.001) for the Haemonetics 30 and COBE 2991 isolated grafts, respectively. The final nucleated cell recoveries after density-gradient separation for these two buffy-coat techniques were 24.2 +/- 10.1% and 29.5 +/- 14.7% (p = 0.30). Compared to manual density-gradient separation, the techniques using the COBE 2991 recovered slightly higher numbers of nucleated cells and CFU-GM. The red blood cell concentration of the 4-HC incubation mixture was 1.0 +/- 0.6% and the CFU-GM survival after treatment was 2.4 +/- 2.6%. The variability in CFU-GM survival after 4-HC incubation of the density-gradient separated grafts appears less than previous experience treating buffy-coat cells. Density-gradient separation of autologous bone marrow appears to provide a more uniform treatment with 4-HC and may improve the clinical transplant course of the autograft recipient.

Bone Marrow↗

PubMed1990

Long-term results with the above-knee popliteal expanded polytetrafluoroethylene graft.

Since approximately 30% to 40% of autogenous vein bypass grafts to the femoropopliteal level may occlude within 5 years of implantation, additional vein will be required for subsequent revisions. We undertook a study to determine whether the preferential use of an above-knee expanded polytetrafluoroethylene bypass graft to save vein is an appropriate option. We reviewed our experience with 114 above-knee expanded polytetrafluoroethylene bypass reconstructions. Life-table analysis of primary and secondary graft patency was carried out by the method of Peto and statistically analyzed for the influence of clinical indication, runoff as determined by both preoperative and intraoperative completion arteriography, smoking, and diabetes. The 5-year primary patency rate of 57% for patients with claudication was comparable to contemporary randomized or retrospective series with below-knee autogenous vein for that indication, and it was superior to the patency rate for limb salvage. The status of the runoff vessels was an important determinant of outcome. The 59 limbs with good arteriographic runoff (2 to 3 vessels) had a markedly higher 5-year patency rate (70%) than the poor arteriographic runoff (0 to 1 vessels) group (30%). Continued cigarette smoking and diabetes mellitus also appeared to affect adversely primary graft patency in our hands. Our data support the use of preferential above-knee expanded polytetrafluoroethylene grafts in patients with good angiographic runoff. This approach does not appear to prejudice the limb against secondary revisionary procedures or the use of a new autogenous graft, if required.

Adult↗

PubMed1988

A new primate model for the study of intravenous thrombotic potential and its modification.

Advances in venous reconstruction have been limited by inherent venous thrombogenicity and the absence of a suitable prosthetic material for use in the venous system. We have designed an in vivo experimental model to evaluate early blood-material interactions within the venous system and to quantitate drug efficacy in the alteration of platelet function and fibrin deposition in the baboon. An 8F catheter was placed percutaneously in the femoral vein of an adult male baboon. Indium 111-labeled autogenous platelets or iodine 125-labeled human fibrinogen was infused before the introduction, into the inferior vena cava, of a linear array of 5 x 15 mm alternating Dacron and polytetrafluoroethylene samples attached to a benzalkonium-heparin-treated guide wire. At 60 or 120 minutes the samples were removed and a 1 ml aliquot of blood was drawn. The materials and blood samples were counted in a gamma well counter, and the material counts were normalized to the circulating label present in the 1 ml blood sample. The experiment was repeated after pretreatment with heparin, aspirin, or dextran. Whole blood clotting times and bleeding times were monitored. The results showed decreased platelet and fibrin deposition on polytetrafluoroethylene when compared with Dacron in the venous system. Aspirin, heparin, and dextran were all found to decrease platelet and fibrin deposition onto intravenously placed graft material samples (p less than 0.05, Student's t test). The data confirm the ability of the model to evaluate quantitatively anticoagulants, antiplatelet agents, and prospective graft materials for use in venous reconstructions.

Animals↗

PubMed1987

CFU-GM content of bone marrow graft correlates with time to hematologic reconstitution following autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide-purged bone marrow.

Autologous bone marrow transplants (BMTs) can repopulate the hematologic system of patients treated with marrow-ablative chemotherapy and/or radiotherapy. However, treatment of the bone marrow graft to eliminate residual tumor cells prior to reinfusion can delay the return of peripheral blood elements, presumably from damage to or loss of hematopoietic stem cells responsible for hematologic recovery. To develop a model predictive of hematologic recovery, we studied the progenitor cell contents of 4-hydroperoxycyclophosphamide (100 micrograms/mL)-purged bone marrow grafts of 40 consecutive patients undergoing autologous BMT at this center. Granulocyte-macrophage colonies (CFU-GM) were grown from all grafts after treatment with this chemotherapeutic agent, but erythroid (BFU-E) and mixed (CFU-GEMM) colonies were grown from only 44% and 33% of the grafts respectively. The recovery of CFU-GM after purging ranged from 0.07% to 23%. The logarithm of CFU-GM content of the treated grafts was linearly correlated with the time to recovery of peripheral blood leukocytes (r = -0.80), neutrophils (r = -0.79), reticulocytes (r = -0.60), and platelets (r = -0.66). The CFU-GM content of purged autologous bone marrow grafts may reflect the hematopoietic stem cell content of the grafts and thus predict the rate of hematologic recovery in patients undergoing autologous BMT.

Adolescent↗