Biomedical subjects

M Goldman

Publications and source records attributed to M Goldman.

At least 37 records · Page 2Linked to original sources

PubMed2003

OM197-MP-AC induces the maturation of human dendritic cells and promotes a primary T cell response.

Dendritic cell (DC) maturation is critical for the induction of antigen-specific T lymphocyte responses and may be essential for the development of human vaccines relying on T cell immunity. We investigated the effects on human DC of OM-197, a synthetic pseudodipeptide derived from amino acids, linked to three fatty acid chains and devoid of endotoxin properties. OM-197 upregulated the expression of HLA-DR, CD80, CD86, CD83, CD40 and CD54 at the surface of myeloid DC naturally present in blood as well as of DC generated in vitro from monocytes using IL-4 and GM-CSF. OM-197 also induced the release of IL-12 and TNF-alpha from DC. Finally, DC incubated with OM-197 after pulsing with hepatitis B surface antigen (HBs Ag) induced in vitro expansion of IFN-gamma-secreting HBs Ag-specific CD4(+) T lymphocytes from naive individuals. Taken together, these data identify OM-197 as a potential vaccine adjuvant for the induction of Th1-type responses.

CD4 Antigens↗

PubMed2003

Report on the Eleventh International Society of Blood Transfusion Platelet Genotyping and Serology Workshop.

BACKGROUND AND OBJECTIVES: The aims of the Eleventh International Workshop were to evaluate proficiency in platelet genotyping and antibody detection, to equip laboratories to perform Gov antigen system genotyping and antibody detection, and to evaluate the laboratory and clinical approach to cases of neonatal alloimmune thrombocytopenia (NAIT). MATERIALS AND METHODS: There were 34 participating laboratories from 22 countries on five continents. Participating laboratories were provided with 10 DNA samples, 15 unknown sera, and three monoclonal antibodies for titration, as well as primer pairs and a protocol for Gov genotyping and Gov antibody screening. They were also provided with a questionnaire on investigation and clinical management of patients with NAIT. RESULTS: Thirty-three participants reported human platelet antigen (HPA)-1, -2, -3 and -5 genotyping results, 25 reported HPA-4 typing results, 17 reported HPA-6 typing results and 24 reported Gov typing results. For HPA-1-6 genotyping, 23 laboratories were concordant with a majority vote for all allotypes tested, five laboratories reported one deviation, three laboratories reported two deviations and one laboratory reported three deviations. For Gov genotyping, six deviations occurred in three of the 24 laboratories reporting results. Antibody detection was 90% concordant for anti-HPA-1a, anti-HPA-5a and anti-HPA-5b detection. Anti-HPA-2b and anti-Gova were detected by 20 and 14 out of 33 laboratories, respectively. Approaches to the clinical management of NAIT vary widely, especially for mothers with a history of a previous infant with mild NAIT. CONCLUSIONS: The overall error rate for HPA-1-6 genotyping decreased from 2.7% in the tenth workshop to 0.8% in the eleventh workshop. The majority of laboratories were able to perform Gov genotyping, although the error rate was 7.5%. Detection of common clinically significant antibodies was good, although detection of the much rarer HPA-2b was problematic. There was considerable progress in the detection of anti-Gova. The lack of consensus over treatment of NAIT demonstrates uncertainty over optimal management of these patients.

Antigens, Human Platelet↗

PubMed2003

Relapse of coccidioidomycosis despite immune reconstitution after fluconazole secondary prophylaxis in a patient with AIDS.

We report a case of relapse of coccidioidomycosis in an HIV-infected person who discontinued maintenance azole therapy following a response to antiretroviral therapy. This experience raises concern about the safety of withholding secondary prophylaxis for coccidioidomycosis in persons with HIV infection who have achieved immunological responses to antiretroviral therapy.

AIDS-Related Opportunistic Infections↗

PubMed2003

Symptoms are an important outcome in chronic obstructive pulmonary disease clinical trials: results of a 3-month comparative study using the Breathlessness, Cough and Sputum Scale (BCSS).

The need to manage the key symptoms of chronic obstructive pulmonary disease (COPD) (breathlessness, cough and sputum) is an important treatment objective. Viozan (sibenadet HCl, AR-C68397AA) is a novel dual D2 dopamine receptor, beta2-adrenoceptor agonist, which combines conventional bronchodilatory activity with the sensory nerve modulation afforded by dopamine agonism. The efficacy of this agent in relieving patient symptoms has been determined in a series of large-scale clinical studies; the results of a 3-month, placebo-controlled multi-centre study are reported. Effect on patient symptoms was determined using a novel patient-reported assessment instrument, the Breathlessness, Cough and Sputum Scale (BCSS). Patients with smoking-related COPD were required to complete a 2-week baseline period before being randomized to one of three treatment groups; sibenadet (500 microg three times daily) plus placebo (twice daily); salmeterol (50 microg twice daily) plus placebo (three times daily); placebo (twice daily) plus a second placebo (three times daily). All treatments were delivered via pressurized metered dose inhaler (pMDI) for 12 weeks. From enrolment, patients were required to complete daily diary cards to record symptoms of breathlessness, cough and sputum, medication use and adverse events. The primary outcome measure was the difference between the mean BCSS total score measured over the baseline period and the mean BCSS total score in the final 4 weeks of the treatment period. Secondary measures included assessment of lung function, rescue medication use, exacerbations, health-related quality of life, opinion of efficacy and safety. Although an initial reduction in BCSS total score (indicating symptom improvement) was seen with sibenadet therapy, this effect was not maintained for the study duration. Salmeterol therapy, however, resulted in a sustained reduction in BCSS total score. No notable benefit over placebo was seen in lung function, exacerbations or health-related quality of life with either active treatment. While the results of this study failed to demonstrate sustained efficacy with sibenadet therapy, they do indicate the value of symptom assessment in the clinical evaluation of new drugs for the treatment of COPD.

Administration, Inhalation↗

PubMed2003

Long-term use of Viozan (sibenadet HCl) in patients with chronic obstructive pulmonary disease: results of a 1-year study.

Viozan (sibenadet HCl, AR-C68397AA) is a novel dual D2 dopamine receptor, beta2-adrenoceptor agonist that has been investigated for efficacy in alleviating the symptoms of chronic obstructive pulmonary disease (COPD). The slowly progressive nature of this disease means that patients will require ongoing therapeutic management for many years, or even decades. With such long-term treatment, the safety profile of new agents will be of paramount importance. As part of the large-scale assessment of sibenadet, a 12-month safety study has been conducted. Following completion of a 2-week baseline period, 435 adults with stable, symptomatic, smoking-related COPD were randomized to receive either 500 microg sibenadet or placebo delivered via pressurized metered dose inhaler (pMDI), three times daily for 52 weeks. Sibenadet therapy was generally well tolerated, with the only notable differences seen in the incidence of tremor and taste of treatment (16.9% vs. 4.1% and 14.5% vs. 4.1% in the sibenadet and placebo groups respectively). There were a total of 79 patients with serious adverse events (SAEs), 43 (14.8%) in the sibenadet pMDI group and 36 (24.8%) in the placebo group. No clinically significant abnormal laboratory values or overall differences between treatment groups were noted. Similarly, there were no clinically significant differences between the two treatment groups for cardiac variables, or in vital signs. The secondary variables showed no notable differences with respect to lung function, exacerbations or health-related quality of life. Due to the effective beta2-agonist properties, patients in the sibenadet group did, however, report reduced rescue medication usage at all timepoints. While the results of this study show that, overall, sibenadet therapy was well tolerated, the lack of sustained benefit reported in large-scale clinical efficacy studies means that sibenadet development will not be continued.

Administration, Inhalation↗

PubMed2003

Conclusion. Lessons from the novel D2 dopamine receptor, beta2-adrenoceptor agonist, Viozan: chronic obstructive pulmonary disease and drug development implications.

The development of novel drugs for the treatment of chronic obstructive pulmonary disease (COPD) poses significant challenges. The mechanisms through which the chronic symptoms of COPD arise are poorly understood, making identification of potential therapeutic targets and in vivo evaluation of potential therapies extremely difficult. Despite these challenges, a unique approach of combined D2 dopamine, beta2-adrenoceptor agonism was identified as a valid potential target for the treatment of key COPD symptoms, the therapeutic potential of which was investigated in a series of preclinical evaluations. Subsequent clinical assessment has amassed a wealth of data from over 4000 patients, providing valuable insights into COPD, clinical trial design and the value of patient self-assessment tools.

Adrenergic beta-2 Receptor Agonists↗

PubMed2003

Neonatal alloimmune thrombocytopenia due to anti-HPA-2b (anti-Koa).

Most severe cases of neonatal alloimmune thrombocytopenia (NAIT) are due to anti-HPA-1a (anti-PlA1) antibodies. We report a case of NAIT due to anti-HPA-2b that resulted in in utero intracranial hemorrhage.A 33-year-old G2P1A0 Caucasian woman had a routine ultrasound at 34 weeks. The fetus appeared to have a left hemispheric hematoma. IVIG, 1g/kg, was started immediately and administered weekly until delivery. One day after receiving the first dose of IVIG, fetal platelet count was 18 x 10(9)/L, and Hb was 116 g/L. Eleven mL of matched platelets compatible by monoclonal antibody immobilization of platelet antigens (MAIPA) assay were transfused in utero, raising the platelet count to 62 x 10(9)/L. Repeat transfusions were done later that week and 1 week later, with pretransfusion counts of 19 x 10(9)/L and 16 x 10(9)/L, respectively. Delivery by C section was done at 35.5 weeks, after the third platelet transfusion. Platelet count at birth was 77 x 10(9)/L. Drainage of the hematoma was performed after transfusion. Testing with a solid phase ELISA revealed reactivity against GP1b/IX. MAIPA testing after platelet treatment with the protease inhibitor leupeptin demonstrated the presence of anti-HPA-2b. On PCR-SSP the mother was HPA-2a homozygous, the father was HPA-2a/2b. Antibodies against the HPA-2b antigen located on the GP1b/IX complex have been reported in rare cases of NAIT. Testing is complicated by proteolytic degradation of the antigen-bearing fragment. Compatible platelets are easily found since approximately 85 percent of donors are HPA-2a/2a.

Journal Article↗

PubMed2002

Nasal midazolam as a novel anticonvulsive treatment against organophosphate-induced seizure activity in the guinea pig.

Seizures and status epilepticus, which may contribute to brain injury, are common consequences of exposure to organophosphorus (OP) cholinesterase inhibitors. Effective management of these seizures is critical. To investigate the efficacy of nasal midazolam as an anticonvulsive treatment for OP exposure, as compared to intramuscular midazolam, guinea pigs were connected to a recording swivel for electrocorticograph (ECoG) monitoring and clinical observation. The experimental paradigm consisted of pyridostigmine pretreatment (0.1 mg/kg i.m.) 20 min prior to sarin exposure (1.2x LD(50,) 56 micro g/kg i.m.). One minute post-exposure, atropine (3 mg/kg i.m.) and TMB-4 (1 mg/kg im) were administered. Within 3-8 min after sarin exposure all animals developed electrographic seizure activity (EGSA), with convulsive behavior. Treatment with midazolam (1 mg/kg i.m.) 10 min after the onset of EGSA abolished EGSA within 389+/-181 s. The same dose was not effective, in most cases, when given 30 min after onset. However, a higher dose (2 mg/kg) was found efficacious after 30 min (949+/-466 s). In contrast, nasal application of midazolam (1 mg/kg) was found most effective, with significant advantages, in amelioration of EGSA and convulsive behavior, when given 10 min (216+/-185 s) or 30 min (308+/-122 s) following the onset of EGSA ( P<0.001). Thus, nasal midazolam could be used as a novel, rapid and convenient route of application against seizure activity induced by nerve agent poisoning.

Administration, Intranasal↗

PubMed2002

Mucosal and invasive fungal infections in HIV/AIDS.

Advances in the management of fungal infections in AIDS justify this review. First, their incidence has fallen with the introduction of potent antiretroviral therapy. Now, most cases occur in patients with advanced HIV disease who have failed multiple antiretroviral regimens, are nonadherent to therapy, or treatment na ve. Immune reconstitution has reduced the incidence of these infections and permitted discontinuation of maintenance therapy. However, the immune response to antiretroviral therapy has resulted in paradoxical worsening in some cases, "so-called immune reconstitution inflammatory syndromes". Finally, new antifungal agents expand our treatment choices. This review updates management of fungal infections in AIDS.

AIDS-Related Opportunistic Infections↗

PubMed2002

In vitro behavior of silicate glass coatings on Ti6A14V.

The in vitro response in simulated body fluid (SBF) of silicate glass coatings on Ti6A14V was evaluated. Glasses belonging to the SiO2-CaO-MgO-Na2O-K2O-P2O5 system were used to prepare 50-70 m thick coatings on Ti6Al4V, employing a simple enameling technique. Glasses with silica content higher than 55 wt% can be used to prepare coatings that do not crack or delaminate and exhibit good adhesion to the alloy. It has been found that coatings with silica content lower than 60 wt% are more susceptible to corrosion and precipitate carbonated hydroxyapatite on their surface during in vitro tests. However, these coatings have a higher thermal expansion than the metal and are under tension. After 2 months in SBF cracks grow in the coating that reach the glass/metal interface and initiate delamination. Glasses with silica content higher than 60 wt% are more resistant to corrosion and have lower thermal expansion. These coatings do not crack but they do not precipitate apatite even after 2 months in SBF.

Alloys↗

PubMed2002

Incidence of histoplasmosis following allogeneic bone marrow transplant or solid organ transplant in a hyperendemic area.

Questions have arisen regarding the risk of developing symptomatic Histoplasma capsulatum infection among patients who undergo transplant-related immunosuppression in areas endemic for histoplasmosis. Our medical center is located in a hyperendemic area for histoplasmosis, where three large outbreaks occurred since 1978. We undertook a retrospective chart review of 137 patients who received allogeneic bone marrow transplant and of 449 patients who received solid organ transplant from January 1994 to December 1996 in order to assess the incidence of active histoplasmosis. Charts were reviewed before and after transplantation for clinical outcomes, H. capsulatum serologies and antigen results, and microbiological and radiological results. After a mean follow-up duration exceeding 16 months, no patient was diagnosed with histoplasmosis. In the absence of an outbreak, histoplasmosis is a rare infection following the immunosuppression of allogeneic bone marrow or solid organ transplantation even in a hyperendemic area. Pre-transplant serologies or chest radiographs consistent with prior infection were not associated with post-transplant histoplasmosis.

Adult↗

PubMed2002

Clinical characteristics of 13 solid organ transplant recipients with ganciclovir-resistant cytomegalovirus infection.

BACKGROUND: Ganciclovir-resistant (GCV-R) cytomegalovirus (CMV) is now being reported with increasing frequency in solid organ transplant recipients. OBJECTIVE: To describe the clinical characteristics and outcomes of all solid organ transplant patients with GCV-R CMV seen between 1990 and 2000 at a single center. METHODS: Patients with clinically suspected GCV resistance had viral isolates subjected to phenotypic analysis by plaque reduction assay, and also genotypic analysis. Medical records of the 13 patients with GCV-R CMV were reviewed for demographic, microbiologic, clinical, and pathologic data. RESULTS: Thirteen patients were identified, including 5 kidney, 1 heart, and 7 lung transplant recipients. All but one patient (92%) were CMV donor seropositive, recipient negative (D+/R-), and 11/13 (85%) had tissue-invasive CMV. CMV viremia was recurrent in 9/13 (69%); in 2 others, the first CMV episode was fatal. Overall, 9/13 (69%) of patients have died, all of CMV or its complications. Of the 10 who received foscarnet, only one survived. All patients had received GCV-based prophylactic regimens; 8/13 patients (62%) had received CMV hyperimmune globulin (CMVIG) as part of prophylaxis, 6/13 (46%) had received oral ganciclovir, and 5/13 (38%) had received intermittent (3 x/week) IV ganciclovir for prophylaxis. CONCLUSIONS: GCV-R CMV is associated with CMV D+/R- status, tissue-invasive disease, and high mortality even with foscarnet therapy. Exposure to less than fully therapeutic levels of GCV, in the form of oral or intermittent IV GCV, is common. The use of CMVIG in prophylaxis does not appear to prevent resistance. Further work remains to be done to elucidate the risk factors and optimal mode of prophylaxis and treatment for GCV-R CMV.

Cytomegalovirus↗

PubMed2002

Chlorpheniramine is no more effective than placebo in relieving the symptoms of childhood atopic dermatitis with a nocturnal itching and scratching component.

BACKGROUND: Childhood atopic dermatitis (AD) is a common disorder affecting 15% of children aged over 18 months. AD is associated with intense nocturnal itching. The central sedative effect of antihistamines is thought to be useful in interrupting the itching cycle and may prevent exacerbations. OBJECTIVE: A multi-centred, double-blind, placebo-controlled study was carried out in 155 children to evaluate chlorpheniramine in alleviating symptoms of AD. METHODS: Assessments were carried out over a 4-week study period consisting of 3 visits to out-patient clinics. During the visits the severity of AD and itching was rated using a series of visual analogue scale (VAS) and 5-point rating scales. RESULTS: The use of chlorpheniramine resulted in no greater alleviation of AD symptoms than placebo. CONCLUSIONS: The findings contradict conventional wisdom that the sedative effect of earlier-generation antihistamines alleviates symptoms of AD. The study also indicates that the use of antihistamines in AD does not affect the amounts of topical treatment used over the short term.

Antipruritics↗

PubMed2002

[The immunology-hematology-transfusion department].

New immunotherapies derived from biotechnology offer fascinating perspectives in different fields of medicine including anti-infectious vaccines, cancer, organ transplantation and autoimmune diseases. In this paper, we illustrate how the Department of Immunology can contribute to the development of these new treatments within a academic hospital such as the Erasme Hospital at the Université Libre de Bruxelles.

Allergy and Immunology↗

PubMed2002

[The Erasme Foundation].

Created in 1982 to encourage the scientific research in the Erasme Hospital, the Erasme Foundation has founded 174 research grants, has financially supported the building of the Cellular and Molecular Therapy Unit, and has organized more than 60 lectures in various biomedical fields.

Belgium↗

PubMed2002

Nondetection of the S antigen due to the presence of sodium hypochlorite.

Low concentrations of sodium hypochlorite (chlorine bleach) are known to destroy S antigen on intact fresh red blood cells (RBCs). Sodium hypochlorite is commonly used as a disinfectant. We report nondetection of the S antigen in tube and microplate saline indirect antiglobulin testing (SIAT) with a lot of commercial saline utilized in our donor screening and reference laboratories. Known S+s+ RBCs were found to be nonreactive with anti-S by SIAT in our reference laboratory. Our investigation demonstrated the presence of chlorine in the commercial saline. The saline lot was used for several days of donor screening and recall of FFP and platelet concentrates was initiated. Two lots of saline were recalled from blood banks across North America.

Journal Article↗

PubMed2001

Tumoricidal activity of monocyte-derived dendritic cells: evidence for a caspase-8-dependent, Fas-associated death domain-independent mechanism.

Monocyte-derived dendritic cells (DC) were found to be cytotoxic for several tumor cell lines including Jurkat cells, which were killed through a calcium-independent pathway. K562 cells were resistant, excluding a NK cell-like activity. DC-mediated apoptosis did not involve classical death receptors because it was not reversed by blocking TNF/TNFR, CD95/CD95 ligand, or TNF-related apoptosis-inducing ligand/TNF-related apoptosis-inducing ligand receptor interactions. Fas-associated death domain-deficient, but not caspase-8 deficient, Jurkat cells were killed by DC. Indeed, caspase-8 cleavage was demonstrated in Jurkat cells cocultured with DC, and the use of specific caspase inhibitors confirmed that apoptosis triggered by DC was caspase-8 dependent. Furthermore, the involvement of Bcl-2 family members in the control of DC-mediated apoptosis was demonstrated by Bid cleavage in Jurkat cells cocultured with DC and resistance of Jurkat cells overexpressing Bcl-2 to DC-mediated cytotoxicity. Overall, these data indicate that monocyte-derived DC exert a caspase-8-dependent, Fas associated death domain-independent tumoricidal activity, a finding that could be relevant to their therapeutic use in cancer.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Gene re-arrangement and fusion in Mycoplasma gallisepticum thyA-nrdFEI locus.

Sequencing of Mycoplasma gallisepticum genome fragment containing thymidylate synthase and ribonucleotide reductase gene clusters reveals both its unusual organization and gene content. Sequence analysis indicates the presence of a gene whose product can be considered as a fusion of two full size proteins: the N-terminal part shows significant similarity to mycoplasmal dihydrofolate reductases, while the C-terminal part of the polypeptide chain shows significant similarity to eukaryotic deoxycytidylate deaminase. Phylogenetic analysis has suggested that the C-terminal part of the M. gallisepticum fusion gene and eukaryotic deoxycytidylate deaminase genes are xenologous. No chromosomal regions encoding peptides similar to the C-terminal part of this fusion protein were found in completely sequenced genomes of Mycoplasma genitalium and Mycoplasma pneumoniae. Genes for ribonucleoside diphosphate reductase alpha chain (nrdE), NrdI protein (nrdI), and ribonucleoside diphosphate reductase beta chain (nrdF) have an opposite direction of transcription with respect to genes for thymidylate synthase (thyA), and dihydrofolate reductase-deoxycytidylate deaminase fusion protein.

Amino Acid Sequence↗