PubMed Health⌕ Search

Biomedical subjects

D Warren

Publications and source records attributed to D Warren.

At least 37 records · Page 2Linked to original sources
PubMed1996

Quantal secretion from visualized boutons on rat pelvic ganglion neurones.

Synaptic transmission from single preganglionic hypogastric nerves innervating monopolar pelvic ganglion neurones has been studied with intracellular electrodes to record transmission from all the boutons and with extracellular electrodes placed over boutons visualized with DiOC2(5) in order to record transmission from selected boutons. Intracellular electrodes revealed spontaneous excitatory postsynaptic potentials (EPSPs) with amplitude histograms that show increasing numbers of large EPSPs as the external calcium ([Ca2+]o) was increased from 0.15 to 1.0 mM. These histograms were in general well fitted by a Poisson mixture of gamma distributions. Extracellular electrodes placed over visualized boutons revealed evoked excitatory postsynaptic potentials (extracellular EPSPs) with amplitude histograms that were best described by single gamma distributions in most cases in low [Ca2+]o (less than 0.5 mM). The standard deviation of these gammas was not much larger than that of the electrical noise. In a minority of extracellular recordings the amplitude histogram of evoked extracellular EPSPs was best described by a gamma distribution in which the standard deviation was much greater than that of the noise. Confocal microscopy of boutons orthogradely labelled with dextran-rhodamine showed that about 30% of these formed closely apposing pairs on the surface of the neurones. These observations are discussed in terms of the hypothesis that multiquantal release at boutons occurs as a consequence of the coupled secretion from closely apposed boutons.

Animals↗
PubMed1996

Home-based cardiac rehabilitation and lifestyle modification: the MULTIFIT model.

Managed care has changed the way health care is delivered in the United States. Simultaneously, major changes in the management of patients with coronary heart disease has led to dramatic shifts in cardiac rehabilitation. Exercise training, education, and counseling to modify coronary risk factors has clearly been shown to benefit patients with coronary disease. Moreover, intensive risk factor modification has been shown to prevent progression of coronary atherosclerosis and to lower morbidity and mortality. Newer delivery models of rehabilitation are needed to improve health outcomes in a cost-effective way. A nursing case management model (MULTIFIT), illustrates one such innovative delivery model that meets the needs of a managed care plan for comprehensive cardiovascular risk reduction and surveillance of patients.

California↗
PubMed1996

Specificity and affinity of 26 monoclonal antibodies against the CA 125 antigen: first report from the ISOBM TD-1 workshop. International Society for Oncodevelopmental Biology and Medicine.

The specificity of 26 monoclonal antibodies against the CA 125 antigen was investigated in two phases of the ISOBM TD-1 workshop. The binding specificity was studied using CA 125 immunoextracted by specific antibodies immobilized on various solid phases, or on the surface of human cell lines. Immunometric assays using all possible antibody combinations were used to study the topography of antibody binding sites on the antigen. We conclude that the CA 125 antigen carries only two major antigenic domains, which classifies the antibodies as OC125-like (group A) or M11-like (group B). One antibody, OV 197, showed binding specificity related to some of the OC125-like antibodies, but was classified into a separate group C. The OC125-like group of antibodies has four subgroups with different binding specificities. These are A1 = OC 125 and K 95, A2 = K 93, A3 = B43.13, and A4 = ZS 33, B27.1 and CCD 247. Binding of nonlabelled OC 125 or K 95 to CA 125 caused a marked increase in binding of labelled OV 197 to the complex. This conformational change was not observed with any other antibody combinations. Antibody B43.13 could form immunometric assay combinations particularly with antibodies of subgroup A4, indicating that the B43.13 epitope is in the periphery of the binding area of OC125-like antibodies. The M11-like group of antibodies is more homogenous with strong cross-inhibition between most antibodies. Only one antibody, ZR 38, would form an immunoassay combination with other M11-like antibodies and thus represents a distinct subgroup. The main group of M11-like antibodies are M 11, ZR 45, MA602-6, K 91, OV 185, K 101, K 90, K 96, K 97, K 102, CCD 242, 145-9, and 130-22. Antibody OV 197 binds to a domain designated C and is unique, as stated above. Antibody pairs from any two of the three groups may be used in immunometric assays. Three antibodies were not studied by complete cross-inhibition due to low affinity (OV 198 and K 100) or lack of material (MA602-1). OV 198 and K 100 are most likely OC125-like and MA602-1 is M11-like. Antibody affinity was estimated with labelled antigen in solution or with antigen absorbed on microtiter wells. Western blot analysis showed staining both in the stacking gel and corresponding to a molecule of 200 kDa. There was a marked difference between the antibodies in their ability to bind to CA 125 immobilized on a membrane. Strongest binding was observed with the M11-like antibodies, particularly M 11, K 96, K 97, MA602-6, 145-9. Antibodies belonging to the subgroup A4 were the only OC 125-like antibodies which reacted well with CA 125 in Western analysis. Digestion of CA 125 with proteolytic enzymes showed it to be particularly sensitive to trypsin cleavage. However, no low molecular weight fragments with preserved immunoreactivity were found.

Animals↗
PubMed1996

Double dose-intensive chemotherapy with autologous stem-cell support for metastatic breast cancer: no improvement in progression-free survival by the sequence of high-dose melphalan followed by cyclophosphamide, thiotepa, and carboplatin.

PURPOSE: Twenty-one percent of responding metastatic breast cancer patients remain progression-free a median 50 months following one intensification cycle of cyclophosphamide (6,000 mg/m2), thiotepa (500 mg/ m2), and carboplatin (800 mg/m2) (CTCb) with autologous bone marrow transplantation (ABMT). This trial studied whether the sequence of high-dose melphalan followed by CTCb resulted in improved disease response and duration. METHODS: Women with at least partial responses (PRS) to induction received melphalan (140 or 180 mg/ m2) with peripheral-blood progenitor cell (PBPC) and granulocyte colony-stimulating factor (G-CSF) support. They were monitored as outpatients. After recovery, patients were hospitalized for CTCb with marrow, PBPC, and G-CSF support. RESULTS: Data on 67 women, at a median of 25 months from CTCb, were examined. After melphalan, 49 (73%) required admission for fever (89%), mucositis (35%), or infection (15%) (median stay, 8 days). All received CTCb. For the first 33 patients, the median days from start of melphalan to CTCb was 24. After liver toxicity (one death from venoocclusive disease [VOD]) developed in 11 patients during CTCb, the interval between intensifications was increased to 35 days without incident. Twenty-three patients (34%) are progression-free a median of 16 months post-CTCb. The median progression-free survival (PFS) and survival times for the whole group are estimated at 11 and 20 months, respectively. CONCLUSION: Treatment with this sequence of high-dose melphalan followed by CTCb has not resulted in superior PFS to date, when compared with single-intensification CTCb. This report discusses factors related to patient selection, the role of induced drug resistance, and the schedule of administration of alkylating agenting that may adversely influence outcome.

Adolescent↗
PubMed1996

Immunohistochemical characterization of 22 monoclonal antibodies against the CA125 antigen: 2nd report from the ISOBM TD-1 Workshop.

We evaluated the immunohistological (IH) characteristics of 22 different antibodies that were submitted for study in the frame of the TD-1 ISOBM Workshop on monoclonal antibodies against CA125. Information on relative affinities and epitope similarities was obtained from a parallel immunochemical study. Antibodies were tested at concentrations of 10 and 1 micrograms/ml on frozen and paraffin sections. Paraffin sections were stained according to the streptavidin-biotin complex protocol, and frozen sections according to a two-step immunoperoxidase technique. Aminoethylcarbazole served as the chromogen. The tissues were from normal proliferative endometrium (formalin-fixed paraffin-embedded) material and clear-cell adenocarcinoma of the ovary (formalin-fixed paraffin-embedded and frozen material). Sections were scored for staining in epithelial cells, basal, apical and diffuse cytoplasmic and in stromal components. Intensity was graded as 1, 2 or 3 for epithelial cells and as -1, -2 or -3 for stroma. The cumulative scores for each antibody expressed the discriminative properties of specific epithelial staining against background. M11 and M11-like antibodies, as well as OC125 and OC125-like antibodies, in general showed good staining results. Although there was a trend for high-affinity antibodies to show higher scores, there was no clear relationship between affinity and staining result. For nine antibodies (ZR45, MA602-1, K102, K94, K90, OV185, K97, K96, OV198), the reactions in paraffin and frozen sections were of similar intensity. Most of these were of low affinity with one exception: antibody ZR45, a rat monoclonal antibody (MAb) which had a high relative affinity. For eight antibodies (M11, K101, MA602-6, ZS33, B27.1, B43.13, K93, OC125), a loss of specific staining was observed in frozen sections. All but two of these antibodies (MA602-6 and OC125) were of high relative affinity. With four antibodies (K91, ZR38, K95, K100), the reverse situation was observed. One (K100) was of low affinity, two (K95 and K91) of high affinity and the fourth (ZR38) was a rat MAb of high affinity. Mainly due to the increased cytoplasmic staining in carcinoma, the reactivity in paraffin sections was less extensive in normal endometrium compared to ovarian carcinoma for the majority of antibodies, irrespective of their affinity or epitope group. The IH characterization of these antibodies may be of help in selecting antibodies with specific properties for further comparative studies. The reactivity of normal endometrium with all useful antibodies makes it a good candidate for standard external IH tissue control.

Adenocarcinoma, Clear Cell↗
PubMed1995

Quantal secretion recorded from visualized boutons.

A method is described for recording the electrical signs of transmission at single boutons. Monopolar rat pelvic ganglion cells are electrically compact and receive an innervation from either single hypogastric or pelvic nerves that consists of a set of boutons which innervate the soma of the cells; each bouton possesses an active zone and can be observed with the confocal microscope after dextran-rhodamine orthograde labelling of the hypogastric nerves. Extracellular electrodes of about 8 microns diameter can be positioned in the loose-patch configuration over visualized boutons following their fluorescence with the vital dye, 3,3-diethyloxardicarbocyanine iodide (DiOC2(5)). Excitatory post-synaptic currents (EPSCs), due to stimulation of the hypogastric nerve, can be recorded from boutons in this way, provided that [Ca2+]o is lowered sufficiently to ensure failure of the initiation of the soma action potential by the EPSCs.

Animals↗
PubMed1995

Prognostic factors for prolonged progression-free survival with high-dose chemotherapy with autologous stem-cell support for advanced breast cancer.

PURPOSE: With a median observation time of 50 months from transplant, 13 (22%) of 62 women with metastatic breast cancer treated with high-dose chemotherapy at the Dana-Farber Cancer Institute (DFCI)/Beth Israel Hospital (BIH) remain progression-free. This study determined factors prognostic for prolonged progression-free survival (PFS). METHODS: From June 1988 to January 1992, women who responded to standard chemotherapy received high-dose cyclophosphamide, thiotepa, and carboplatin with autotransplantation. Data encompassing initial breast cancer diagnosis, metastatic presentation, and response to induction treatment were examined for correlations with improved PFS. RESULTS: The 5-year PFS rate for the entire group is estimated to be 21% (95% confidence interval [CI], 10% to 32%). For those patients who attained a complete response (CR) to induction therapy, the 5-year PFS rate is estimated to be 31% (95% CI, 0% to 63%). In univariate analyses, a single metastatic site, CR to induction therapy, prolonged interval from primary diagnosis to first metastases, estrogen receptor (ER)-negative tumors, and older age (> or = 40 years) were associated with prolonged PFS. In multivariate analyses, single metastatic site (P = .002) and attainment of a CR to induction chemotherapy (P = .04) were the most significant predictors for PFS, with a strong trend observed for an interval from primary diagnosis to onset of metastatic disease of 24+ months (P = .066). CONCLUSION: We and others have shown that 10% to 25% of women with metastatic breast cancer are progression-free after high-dose chemotherapy with autotransplantation. Those with chemosensitive disease, minimal tumor bulk, and a prolonged disease-free interval appear to benefit most. Emphasis should continue to focus on the development of more effective cytotoxic regimens and biologic approaches to increase the percentage of patients who may benefit from this approach.

Adolescent↗
PubMed1994

The utility of autopsies in a pediatric emergency department.

The role of the autopsy in verifying clinical diagnosis and as a quality assurance tool in pediatric emergency medicine has not been studied. We reviewed the charts of all children who died soon after arriving at to the pediatric emergency department between October 1985 and December 1989. Opinions as to clinical diagnoses and cause of death were obtained by presenting a summary of patient data, in a blinded fashion, to three emergency pediatricians. Clinical diagnoses were then compared with autopsy diagnoses using the Class Error System. Major diagnostic errors (Class I, Class II) were examined to determine if the autopsy was more useful in any particular patient group. There were 69 children: 36 (52%) were female, and 30 (43%) were infants. Autopsies were performed on 52 (75%) patients. Autopsy diagnoses were categorized as follows: sudden infant death syndrome (SIDS) 14 (27%); underlying disease 15 (29%); trauma 13 (25%); sepsis 8 (16%); and aspiration 2 (4%). No errors were made in 67% of cases. The autopsy confirmed the major clinical diagnosis in 85% of patients. There were no Class I errors. Class II error rate was 15%. Most Class II errors occurred in patients between one and five years of ate (57%), and in patients who had sepsis or underlying disease (95%). Our data show that autopsy is useful in determining the cause of death and may be useful for education and quality assurance in pediatric emergency medicine.

Autopsy↗
PubMed1994

Double dose-intensive chemotherapy with autologous marrow and peripheral-blood progenitor-cell support for metastatic breast cancer: a feasibility study.

PURPOSE: Twenty-seven percent of responding metastatic breast cancer patients remain progression-free a median 29 months following one intensification course of cyclophosphamide (6,000 mg/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) (CTCb) with autologous bone marrow transplantation (ABMT). European investigators report high complete response (CR) rates with melphalan for breast cancer. This trial studied the feasibility of two tandem high-dose intensification therapies in an attempt to optimize disease response and duration. PATIENTS AND METHODS: Women with at least partial responses (PRs) to induction therapy received melphalan (140 to 180 mg/m2), followed 24 hours later by chemotherapy and granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral-blood progenitor cells (PBPCs) and subsequent G-CSF until WBC recovery. The women were monitored as outpatients. After recovery, patients were hospitalized for CTCb with marrow, PBPC, and G-CSF support. RESULTS: Twenty women were assessable. Fourteen (70%) required admission for fever (10% infection) or mucositis (35%) after melphalan (median stay, 5 days). Median days of absolute neutrophil count (ANC) less than 500/microL and platelet count less than 20,000/microL were 6 and 5.5, respectively. Patients received CTCb 25 days after starting melphalan and had a hospital stay of 25 days. After CTCb, median days of ANC less than 500/microL and platelet count less than 20,000/microL were 11.5 and 24, respectively. Grade 3 toxicities included venoocclusive disease (VOD) (10%), mucositis (45%), and infection (20%). Toxicities were reversible without mortality. CONCLUSION: With mobilized PBPCs and growth factors, double dose-intensive chemotherapy is feasible with acceptable toxicity. When compared with trials using marrow alone, these supportive adjuncts decrease sepsis and organ toxicity. The concepts of dose and dose-intensity may now be more effectively and safely studied in chemosensitive tumors, including breast cancer.

Adult↗
PubMed1994

The trading of sex for drugs or money and HIV seropositivity among female intravenous drug users.

OBJECTIVES: Data from 538 women in a cohort study recruited in 1988-1989 were analyzed to determined whether trading sex for drugs or money was independently associated with human immunodeficiency virus (HIV) seroprevalence in a population of female intravenous drug users. METHODS: The women were grouped according to the number of partners with whom they reported trading sex for drugs or money during the previous 10 years: none, 1 through 49 (low), or 50 or more (high); the prevalence of HIV seropositivity in the three groups was 23.2%, 23.7%, and 47.6%, respectively. Logistic regression was used to compare the low- and high-trade groups separately with the group that reported no trading. RESULTS: Low trading was not associated with seroprevalent HIV infection. In a multivariate model, high trading (compared with no trading) was significantly associated with HIV seropositivity after adjustment for cocaine use, history of sexually transmitted diseases, and duration of intravenous drug use. CONCLUSIONS: These data indicate that, among intravenous drug-using women, high levels of trading sex for drugs or money were independently associated with HIV infection. This group needs to be targeted for further intensive intervention.

Adult↗
PubMed1993

Differences in risk factors for human immunodeficiency virus type 1 seroconversion among male and female intravenous drug users.

To examine sex-specific risk factors for human immunodeficiency virus (HIV) type 1 seroconversion among intravenous drug users, the authors conducted a nested case-control study in Baltimore, Maryland, from 1988 to 1992 comparing 146 seroconverters and 539 HIV seronegative controls. Controls were matched on sex, race, date of study entry, and duration of follow-up. Risk factor data were obtained from interviews conducted at the first seroconversion visit for the case and the closest visit for the corresponding seronegative control. Since test results were not available until several weeks after interview, both interviewers and participants were unaware of seroconversion status at the time of interview. When data were analyzed using conditional logistic regression techniques, the variables which were significantly associated with seroconversion among male intravenous drug users included age less than 35 years, a sexually transmitted disease within the past 6 months, lifetime history of syphilis, and current intravenous drug use with an abscess at the injection site. Among women, only a history of three or more sex partners was positively associated with seroconversion and having a biological child under age 18 years was inversely associated with HIV seroconversion. Although the small sample size may have limited the ability to ascertain differences in risks of seroconversion among males and females, these data suggest that sexual transmission contributes to HIV infection among intravenous drug users, especially women.

Adult↗
PubMed1992

Pain management in advanced cancer.

This article presents a primary care approach to pain management in patients with advanced cancer. Assessment of "total" pain is reviewed along with interdisciplinary care. Pharmacologic and nonpharmacologic therapies are outlined, with emphasis on the correct use of narcotics and adjuvant analgesics.

Analgesics↗
PubMed1991

The Bengali context.

Explore the source record for details and available documents.

History, Modern 1601-↗
PubMed1991

An antagonist to vasoactive intestinal peptide affects cellular functions in the central nervous system.

A vasoactive intestinal peptide (VIP) antagonist was synthesized and used to investigate the interactions of VIP with its receptors present in the central nervous system (CNS). The VIP antagonist is a hybrid peptide consisting of a portion of VIP and a portion of neurotensin, designed to change the membrane permeability of the VIP portion. The hybrid antagonist displaced 80 to 90% of [125I]VIP binding to cell cultures from cerebral cortex, hippocampus or spinal cord. The displacement curve was biphasic, suggesting two binding sites. In the case of cortical astrocytes, the antagonist had a Ki of 45 pM at one site and a Ki of 74 nM at the other. At the lower affinity binding site, the antagonist was about 10-fold more potent than VIP in displacing radiolabeled VIP. The accumulation of cyclic AMP (cAMP) in VIP-stimulated cortical glia cultures was decreased by the new antagonist (EC50, 59 nM). This decrease in cAMP was greater than that achieved in the presence of other putative VIP antagonists. Finally, the addition of 1 nM hybrid antagonist to dissociated spinal cord cultures resulted in a 42% reduction in neuronal cell counts as compared with controls, and the EC50 of this effect was about 30 pM, which corresponded closely to the Ki of antagonist displacement of [125I]VIP binding at the high-affinity site. The antagonist appears to be a competitive blocker for both VIP-mediated increases in cAMP formation or VIP-associated maintenance of neuronal survival in spinal cord cultures. Thus, we describe a potent VIP antagonist which interacts with two functionally distinct VIP receptors in the CNS.

Amino Acid Sequence↗
PubMed1990

Vasoactive intestinal peptide: a neurotrophic releasing agent and an astroglial mitogen.

Vasoactive intestinal peptide (VIP) increases neuronal survival in dissociated spinal cord cultures during a critical period of development. In the present study, two mechanisms contributing to this action of VIP have been observed: 1) VIP was shown to be a secretagogue for neuron survival-promoting activity; and 2) VIP was found to be an astroglial mitogen. A high molecular weight substance (greater than 30 kDa), which increased neuronal survival in tetrodotoxin (TTX)-treated spinal cord cultures, was detected in the medium from nonneuronal cells incubated for 1 hr with 0.1 nM VIP. In addition, 3H-thymidine autoradiography and glial fibrillary acid protein (GFAP) immunocytochemistry were used to show that a 5 day treatment with (VIP) increased astroglial mitosis. This effect was specific for astroglia, as silver grain-positive cells not exhibiting GFAP immunoreactivity did not increase in number after VIP treatment. The dual action of VIP may regulate glial-derived trophic substances that are important for neuronal survival during the course of development.

Animals↗
PubMed1990

High levels of granulocyte and granulocyte-macrophage colony-stimulating factors in cord blood of normal full-term neonates.

Because several human hematopoietic growth factors have been identified and shown to be effective for treatment of congenital or iatrogenic neutropenias, and cord blood contains stimulatory activities for blood-forming cells, we postulated that identification of these factors and analysis of their regulatory role in normal neonates would provide a rationale for their use in treating neonatal infections associated with neutropenia. We studied the plasma levels of granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF, respectively) and the frequency of granulomonopoietic colony-forming cells (CFU-GM) in the umbilical cord blood of normal term neonates. Plasma growth factor levels were measured by a biologic assay. Circulating hematopoietic progenitors were assayed for colony formation with different recombinant growth factors used as exogenous growth stimulators. The cell cycle status of these progenitors was analyzed by the thymidine suicide technique. At birth the leukocyte count (mean +/- SD) was 11.0 +/- 3.9 x 10(9)L and the neutrophil count was 5.6 +/- 2.6 x 10(9)/L. The incidence of CFU-GM was significantly higher in umbilical cord blood than in normal adult peripheral blood (p less than 0.005) with up to 40% of the cells in S phase (less than 10% in normal adults). Plasma levels of G-CSF and GM-CSF at birth were 40.8 +/- 2.8 U/ml and 19.9 +/- 5.2 U/ml, respectively (normal adult plasma levels 2.5 +/- 1.5 U/ml for G-CSF and undetectable for GM-CSF). These high levels of G-CSF and GM-CSF in umbilical cord blood of normal neonates might play a role in maintaining adequate neutrophil production.

Adult↗