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Biomedical subjects

D Scott

Publications and source records attributed to D Scott.

At least 55 records · Page 3Linked to original sources
PubMed2001

Treatment of HIV-associated multicentric Castleman's disease with oral etoposide.

Multicentric Castleman's disease (MCD) is a lymphoproliferative disorder that can be defined based upon both clinical and pathological characteristics. The clinical features of this frequently fatal disease include fever, generalized lymphadenopathy, fatigue, splenomegaly, hepatomegaly, and pancytopenia. Recently, severe forms of this disease have been diagnosed in HIV positive patients. Human herpesvirus type 8 (HHV-8) DNA sequences have been detected in peripheral blood mononuclear cells (PBMCs) of patients with Kaposi's sarcoma and MCD, regardless of HIV infection status. Treatment and outcomes in HIV associated MCD are generally unfavorable. We recently treated two HIV-positive patients diagnosed with aggressive MCD with daily oral etoposide (50 mg). The first patient had relapsed on several occasions despite previous therapy with doxil, paclitaxel, and oral ganciclovir. The second patient was treatment naive. Both patients had HHV-8 detectable by polymerase chain reaction in PBMCs, widespread tumor, and B-type symptoms when therapy was initiated. In both cases remissions (documented by computerized tomography) have been durable, 1.5 and 6 months, respectively, with minimal side effects. Oral etoposide may be a safe, tolerable, and active agent in MCD.

Administration, Oral↗
PubMed2001

Aplysia ror forms clusters on the surface of identified neuroendocrine cells.

The ror receptors are a highly conserved family of receptor tyrosine kinases genetically implicated in the establishment of cellular polarity. We have cloned a ror receptor from the marine mollusk Aplysia californica. Aplysia ror (Apror) is expressed in most developing neurons and some adult neuronal populations, including the neuroendocrine bag-cell neurons. The Apror protein is present in peripheral neuronal processes and ganglionic neuropil, implicating the kinase in the regulation of growth and/or synaptic events. In cultured bag-cell neurons, the majority of the protein is stored in intracellular organelles, whereas only a small fraction is expressed on the surface. When expressed on the cell surface, the protein is clustered on neurites, suggesting that Apror is involved in the organization of functional domains within neurons. Apror immunoreactivity partially colocalizes with the P-type calcium channel BC-alpha1A at bag-cell neuron varicosities, suggesting a role for Apror in organizing neuropeptide release sites.

Age Factors↗
PubMed2001

Influence of actin cytoskeleton on intra-articular and interstitial fluid pressures in synovial joints.

Fibroblast microfilamentous actin (F-actin) influences interstitial fluid pressure via linkages to collagen in rat skin (Berg et al., 2001). The present aims were to determine whether the actin cytoskeleton of synovial endothelium, fibroblasts, and synoviocytes influences in vivo (i) fluid exchange between a joint cavity and synovial microcirculation and (ii) extracellular fluid pressures in joints. Rabbit knee joints were treated intra-articularly with the F-actin disrupting drugs cytochalasin D and latrunculin B while joint fluid pressure P(j) was recorded. In joints injected with small volumes of control solution, P(j) fell with time (-0.05 +/- 0.01 cm H2O x min(-1), mean +/- SEM, n = 9, equivalent drainage rate 3.9 microl x min(-1)). Cytochalasin or latrunculin reversed this in approximately 4 min in vivo; P(j) increased with time, e.g., +0.12 +/- 0.04 cm H2O x min(-1) at 200 microM cytochalasin (equivalent filtration rate into joint 6.6-12.5 microl x min(-1), n = 4), with a cytochalasin EC50 of 45 microM. Plasma gamma-globulin clearance into the joint cavity was also increased. Post mortem, cytochalasin did not reverse dP(j)/dt and had no more effect on P(j) than did control solution. Also, when synovial interstitial fluid pressures were measured by servonull micropipette post mortem (control -0.95 +/- 0.37 cmH2O, n = 18) cytochalasin had no significant effect on interstitial pressure over 60 min, even at 1 mM. It was concluded that synovial endothelial F-actin has an important role in the normal synovial microvascular resistance to fluid filtration and plasma gamma-globulin permeation and is thus a potential link between pro-inflammatory mediators and arthritic joint effusions. The results provided no support for the hypothesis that synoviocyte F-actin influences the swelling tendency of synovial matrix and hence extracellular fluid pressures, in contrast to the findings of Berg et al. (2001) in rat dermis.

Actins↗
PubMed2001

High expression of the trefoil protein TFF1 in interval breast cancers.

Breast cancer screening is important for the early detection of breast cancer. Tumors that become symptomatic in the screening interval are known as interval cancers but the reasons for their rapid progression are unknown. Estrogen receptor expression is lower in interval cancers suggesting that they may have reduced hormonal responsiveness. To investigate this hypothesis we have measured the expression of the estrogen receptor and three estrogen-responsive genes (cathepsin D, progesterone receptor, and TFF1) in screen-detected and interval breast cancers. The expression of the protease cathepsin D was not associated with estrogen receptor in either group of tumor. Progesterone receptor expression was highly correlated with that of the estrogen receptor in both groups of tumors but it was not expressed at significantly different levels in the two groups of tumors. Expression of TFF1, a cellular motogen, was correlated with estrogen receptor in screen-detected but not interval cancers and was expressed at markedly higher levels in interval breast tumors, the group that expresses lower levels of estrogen receptor. Interval cancers are characterized by high levels of expression of TFF1 and/or Ki67 suggesting that cell migration and cell division play important roles in the rapid progression of interval cancers. The observation that TFF1 expression in interval cancers tends to be estrogen-independent and that interval cancers have reduced estrogen receptor expression suggests they may have a reduced response to hormone therapy.

Breast Neoplasms↗
PubMed2001

Characterization of the pharmacology, signal transduction and internalization of the fluorescent PACAP ligand, fluor-PACAP, on NIH/3T3 cells expressing PAC1.

Fluor-PACAP, a fluorescent derivative of PACAP-27, has been confirmed to share a high affinity for PAC1 receptors transfected into NIH/3T3 cells and to have comparable pharmacological characteristics to the unconjugated, native form. Through competitive binding with 125I-PACAP-27, the two ligands exhibited similar dose- dependent inhibition. Additional examination of the efficacy of activating adenylyl cyclase revealed that both ligands analogously stimulated the production of cyclic AMP. Furthermore, PAC1 internalization visualized by our Fluor-PACAP, is compareable to that performed with the radioligand, 125I-PACAP-27, with maximal internalization achieved within thirty minutes. Thus, Fluor-PACAP exhibits intracellular signaling abilities homologous to the native ligand.

3T3 Cells↗
PubMed2001

Establishing an employee baseline purified protein derivative status in the division of immigration health Service Processing Centers.

While the incidence of reportable tuberculosis in United States born persons declined, the number of cases among foreign-born persons increased by 6 percent in 1998. The Immigration and Naturalization Service (INS) processes about 95,000 undocumented aliens annually from countries with a high prevalence of tuberculosis. An effort was made to establish a baseline Purified Protein Derivative (PPD) status of employees of the Division of Immigration Health (DIH) and INS, Services Processing Centers (SPC). This was achieved through a special operation (project) of a one time, two-step, mass PPD testing of all SPC employees on all eleven sites in the United States and Puerto Rico. A reading of > 10mm was considered positive. The operation was optional and open to all SPC employees. Exclusion criteria for the study included a history of PPD skin testing within six months of the operation, past history of positive PPD test and past history of tuberculosis. Preliminary results from El Paso SPC, Texas, which is the largest SPC, showed that of the 148 employees which were tested (67 percent of all employees), 17 (11 percent) were PPD positive. Security officers constituted 100 percent of all positive cases. Eighty-one percent of the employees at El Paso are security officers, eighty-seven percent of whom participated in the study. Only 20 (23 percent) of administrative staff participated in the study. Results from El Paso are suggestive of differences in the pattern PPD positivity among SPC employees. The complete results of the study should provide sound evidence for formulating appropriate policies for establishing an effective employee tuberculosis prevention and surveillance program in the Service Processing Centers.

Emigration and Immigration↗
PubMed2001

Minor H antigens: genes and peptides.

In this review, we describe the evidence from which the existence of non-MHC histocompatibility (H) antigens was deduced, the clinical setting of bone marrow transplantation in which they are important targets for T-cell responses, and the current understanding of their molecular identity. We list the peptide epitopes of the human and murine minor H antigens now identified at the molecular level, their MHC restriction molecules and the genes encoding them. Identification of the peptide epitopes allows T-cell responses to these antigens following transplantation of MHC-matched, minor H-mismatched tissues to be enumerated using tetramers and elispot assays. This will facilitate analysis of correlations with host-versus-graft (HVG), graft-versus-host (GVH) and graft-versus-leukaemia (GVL) reactions in vivo. The potential to use minor H peptides to modulate in vivo responses to minor H antigens is discussed. Factors controlling immunodominance of T-cell responses to one or a few of many potential minor H antigens remain to be elucidated but are important for making predictions of in vivo HVG, GVH and GVL responses and tailoring therapy after HLA-matched bone marrow transplantation and donor lymphocyte infusion.

Alleles↗
PubMed2001

The survivin:fas ratio in pediatric renal tumors.

BACKGROUND/PURPOSE: Apoptosis factors inducing or preventing cell death may govern the behavior of certain tumors. Fas is a pro-apoptotic receptor that induces cell death when bound by its ligand and is expressed at greater levels in pediatric renal tumors of good prognosis. Survivin is a novel inhibitor of apoptosis that is expressed in a cell cycle-dependent manner and is abundantly expressed in several tumors of unfavorable histology. This study evaluates the expression of survivin, as well as the prognostic value of the survivin:fas ratio in various types and stages of pediatric renal tumors. METHODS: Multiple apoptosis mRNA species were quantified by Rnase protection assay (RPA) in 32 pediatric renal tumors and adjacent normal kidney specimens before chemotherapy: Wilms' tumor (WT), n = 9; clear cell sarcoma (CCS), n = 4; rhabdoid tumor of the kidney (RTK), n = 5; mesoblastic nephroma (MN), n = 3 and normal kidney, n = 11. Western Blot and immunocytochemistry were used to confirm survivin protein expression in a selective specimen survey. Follow-up data were obtained on patient outcomes, and antiapoptotic to proapoptotic ratios were calculated and correlated with clinical recurrence of disease. RESULTS: Pediatric renal tumors express greater levels of both pro- and antiapoptotic factors than normal kidney. Survivin and fas appeared to be expressed differentially in the tumor specimens sampled. Five of 10 (50%) tumors that went on to recur expressed survivin, whereas survivin was present in only 2 of 11 (18%) nonrecurrent tumors. Conversely, only 2 of 10 (20%) tumors that recurred were fas positive, whereas 5 of 11 (45%) tumors that did not recur expressed fas. The mean survivin:fas ratio was significantly greater in the 10 tumors that went on to recur after treatment (4 RTK, 3 CCS, 3 WT), than in tumors not recurring (2.16+/-1.4 v 1.0+/-1.07; P =.01, Kruskal-Wallis test). The positive predictive value of tumor recurrence was 85.7% (CI: 42.1%, 99.6%) and the negative predictive value was 71.4% (CI: 41.9%, 91.6%) when a cutoff ratio of 1.6 was considered. CONCLUSIONS: The survivin:fas mRNA ratio is of prognostic value in its ability to predict recurrent disease in children undergoing treatment for pediatric renal tumors. In this series, a ratio of greater than 1.6 predicted recurrent disease with a high probability irrespective of clinical stage or pathologic type. Determining the survivin:fas ratio may guide treatment, follow-up and counseling of patients with pediatric renal tumors.

Apoptosis↗
PubMed2001

The inhibitor of apoptosis protein survivin is associated with high-risk behavior of neuroblastoma.

BACKGROUND/PURPOSE: Apoptotic factors inducing or preventing cell death may intrinsically govern the behavior of some tumors. Survivin is a recently described member of the inhibitor of apoptosis protein (IAP) family, that is expressed in a cell cycle-dependent manner and is found in tumors of unfavorable histology. This study examines the presence of several apoptotic factors, including survivin, in neuroblastoma (NB) tumors. Clues to survivin's function in NB are provided by examining its association with behavior and cell dynamics in tumors and cell lines. METHODS: Expression of a panel of apoptosis factors were quantified in 15 NB and related tumors before chemotherapy and in 3 NB cell lines (NB7, NB10, and NB16). Survivin and other apoptotic factors, as well N-myc amplification in primary tumors was correlated with recurrent disease and outcome. Proliferation rate, apoptosis assays, cell cycle analysis, and drug- or immune-mediated cell death were assessed in cell lines and evaluated in the context of differential survivin and apoptosis gene expression. RESULTS: All 7 tumors that went on to recur expressed survivin, whereas expression was absent in all 8 tumors that went into remission. N-myc was amplified in 4 (57.1%) of the 7 recurrent tumors. Of the 8 tumors that were cured, Fas was expressed in 3 (38%), TRAIL-R1 in 6 (75%) and tumor necrosis factor (TNF)-R1 in 8 (100%), whereas these pro-apoptotic receptors were present in only 1 (14%), 1 (14%), and 4 (57%) of the 7 tumors that went on to recur, respectively. Of the 3 cell lines, NB10 expressed the least survivin, displayed the lowest proliferation index, and had the fewest number of cells in the G2/M (mitotic) phase of the cell cycle. Furthermore, NB10 also was most sensitive to TNF-related apoptosis-inducing ligand (TRAIL) or etoposide-induced cell death. CONCLUSIONS: In primary NB tumors, survivin expression was associated with tumors of high risk and unfavorable prognosis, whereas pro-apoptotic receptor expression was more abundant in tumors of favorable prognosis. In this small series, survivin expression appeared to be more predictive of recurrent disease than N-myc amplification. In cell lines, survivin expression was cell cycle dependent, and its expression was associated with greater proliferation rates and greater resistance to drug- or immune-mediated cell death. Survivin expression may become a useful prognostic marker in NB and could be a potential target for the treatment of this tumor. J Pediatr Surg 36:1785-1791.

Apoptosis↗
PubMed2001

Home enteral tube feeding following cerebrovascular accident.

BACKGROUND AND AIMS: In the UK, cerebrovascular accident (CVA) is the third commonest cause of death and the commonest diagnosis in patients receiving home enteral feeding (HETF). This study aimed to use data from the British Artificial Nutrition Survey (BANS) collected between 1996 and 1999 to assess the outcome of patients on HETF, including mortality, return to oral feeding, level of physical activity, and level of dependency, which has resource implications. RESULTS: it is estimated that about 1.7% of all patients suffering a CVA in the UK between 1996 and 1999 received HETF. At one year, 29.6% died while receiving HETF and another 13% returned to oral feeding. Mortality increased with age and was twice as high in those managed in nursing homes compared to those in their own homes. The patients receiving tube feeding spent only 0.6% of their time in hospital. A total of 43.9% of patients were bed-bound at home (1.9% unconscious) and an additional 30.3% were house-bound. Only 21.2% were independent, and the majority were totally dependent on their carers. In CVA patients on HETF the level of dependency was greater than for those with all types of diagnoses (n=12,997). CONCLUSION: This study has described the outcome of a large number of patients receiving HETF in the UK. Since patients spent less than 1% of their time in hospital, HETF relieves pressure on the expensive hospital environment, but places more demands on the carers, who have to deal with severely disabled patients. Recovery of swallowing function should be assessed intermittently to prevent unnecessary HETF.

Adolescent↗
PubMed2001

Interstitial pressure gradients around joints; location of chief resistance to fluid drainage from the rabbit knee.

The hypothesis has been advanced that synovium offers the main resistance to fluid escape from joints, even though it is under 20 microm thick. To test this, fluid was infused into the knee joint cavity of anaesthetised rabbits to set up a pressure gradient, then the profile of periarticular interstitial fluid pressure (P(if)) was measured by advancing a micropipette, connected to a servo-null pressure recorder, in steps through a periarticular tissue 'window' until the joint cavity was entered. With intra-articular pressure (P(j)) raised to 15 cmH(2)O (the pressure of an acute joint effusion) the pressure gradient dP(if) /dx (where x is distance) across the synovial lining was 0.47 +/- 0.04 cmH(2)O microm(-1) (n = 10 joints). This was 23.5-fold greater than the gradient in the subsynovium (0.02 +/- 0.01 cmH(2)O microm(-1); P < 0.0001, Student's t test), indicating that the hydraulic resistivity of the subsynovium is 4 % of that of the synovium. The pressure profile was not altered by circulatory arrest. To test the hypothesis further, the effect of a stab perforation of the synovial lining on fluid drainage rate ((.Q(s)) was studied. Perforation raised both.Q(s) and the conductance term d.Q(s)/dP(j) more than 10-fold (n = 6 joints; P < 0.0001, ANOVA). The results thus support the view that, despite its thinness, the synovial lining offers the main hydraulic resistance to fluid drainage from a synovial joint.

Animals↗
PubMed2001

Foot length, an accurate predictor of nasotracheal tube length in neonates.

BACKGROUND: Existing guidelines for optimal positioning of endotracheal tubes in neonates are based on scanty data and relate to measurements that are either non-linear or poorly reproducible in sick infants. Foot length can be measured simply and rapidly and is related to a number of external body measurements. OBJECTIVES: To evaluate the relation of foot length to nasotracheal length in direct measurements at post mortem examinations, and then compare its clinical relevance with traditional weight based estimates in a randomised controlled trial. METHODS: The dimensions of the upper airway were measured at autopsy in 39 infants with median (range) postmenstrual age and birth weight of 32 (24-43) weeks and 1630 (640-3530) g. The regression equations with 95% prediction intervals were calculated to estimate the optimal nasotracheal length from foot length. In a randomised trial, 59 neonates were nasally intubated according to foot length and body weight based estimates to assess the achievement of "optimal" and "satisfactory" tube placements. RESULTS: In the direct measurements of the airway at autopsy, foot length was a better predictor of nasotracheal distances (r(2) = 0.79) than body weight, gestational age, and head circumference (r(2) = 0.67, 0.58, and 0.60 respectively). Measurement of foot length was easy and highly reproducible. In the randomised controlled trial, there were no significant differences between the foot length and body weight based estimates in the rates of optimal (44% v 56%) and satisfactory (83% v 72%) endotracheal tube placements. CONCLUSIONS: Foot length is a reliable and reproducible predictor of nasotracheal tube length and is at least as accurate as the conventional weight based estimation. This method may be particularly valuable in sick unstable infants.

Analysis of Variance↗
PubMed2001

Monitoring service development through audit.

Comparative audits can be used as important tools for shaping service provision. Short stay facilities offer a more flexible and efficient approach to managing acute paediatric referrals. Users and providers views of the service are important. Children can be safely observed and discharged with parents empowered to continue care. Appropriate support systems should be in place in order to provide an ambulatory service.

Emergency Service, Hospital↗
PubMed2001

Bimanual haptic workstation for laparoscopic surgery simulation.

Realistic laparoscopic surgical simulators will require real-time graphic imaging and tactile feedback. Our research objective is to develop a cost-effective haptic workstation for the simulation of laparoscopic procedures for training and treatment planning. The physical station consists of a custom-built frame into which laparoscopic trocars and surgical tools may be attached/inserted and which are continuously adjustable to various positions and orientations to simulate multiple laparoscopic surgical approaches. Instruments inserted through the trocars are attached to end effectors of two haptic devices and interfaced to a high speed PC with fast graphics capability. The haptic device transduces 3D motion of the two manually operated surgical instruments into slave maneuvers in virtual space. The slave instrument tips probe the simulated organ. Simulations currently in progress include: 1) Surface-only renderings, deformation, and haptic interactions with elements in the gall gladder surgical field; 2) Voxel-based simulations of the bulk manipulation of tissue; 3) laparoscopic herniorrhaphy. This system provides force feed-forward from the grasped tools to the contact tissue in virtual space, with deformation of the tissue by the virtual probe, and force feedback from the deformed tissue to the operator's hands.

Computer Graphics↗
PubMed2000

Early Permian bipedal reptile.

A 290-million-year-old reptilian skeleton from the Lower Permian (Asselian) of Germany provides evidence of abilities for cursorial bipedal locomotion, employing a parasagittal digitigrade posture. The skeleton is of a small bolosaurid, Eudibamus cursoris, gen. et sp. nov. and confirms the widespread distribution of Bolosauridae across Laurasia during this early stage of amniote evolution. E. cursoris is the oldest known representative of Parareptilia, a major clade of reptiles.

Animals↗