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Biomedical subjects

M Whelan

Publications and source records attributed to M Whelan.

At least 19 recordsLinked to original sources
PubMed2004

Control of heterologous hepatitis C virus infection in chimpanzees is associated with the quality of vaccine-induced peripheral T-helper immune response.

Prophylactic hepatitis C virus (HCV) vaccine trials with human volunteers are pending. There is an important need for immunological end points which correlate with vaccine efficacy and which do not involve invasive procedures, such as liver biopsies. By using a multicomponent DNA priming-protein boosting vaccine strategy, naïve chimpanzees were immunized against HCV structural proteins (core, E1, and E2) as well as a nonstructural (NS3) protein. Following immunization, exposure to the heterologous HCV 1b J4 subtype resulted in a peak of plasma viremia which was lower in both immunized animals. Compared to the naïve infection control and nine additional historical controls which became chronic, vaccinee 2 (Vac2) rapidly resolved the infection, while the other (Vac1) clearly controlled HCV infection. Immunization induced antibodies, peptide-specific gamma interferon (IFN-gamma), protein-specific lymphoproliferative responses, IFN-gamma, interleukin-2 (IL-2), and IL-4 T-helper responses in both vaccinees. However, the specificities were markedly different: Vac2 developed responses which were lower in magnitude than those of Vac1 but which were biased towards Th1-type cytokine responses for E1 and NS3. This proof-of-principle study in chimpanzees revealed that immunization with a combination of nonstructural and structural antigens elicited T-cell responses associated with an alteration of the course of infection. Our findings provide data to support the concept that the quality of the response to conserved epitopes and the specific nature of the peripheral T-helper immune response are likely pivotal factors influencing the control and clearance of HCV infection.

Animals↗
PubMed2003

Estimating the sensitivity and specificity of matching name-based with non-name-based case registries.

Because non-name-based case registries have recently been used for reporting human immunodeficiency virus infection, this study attempted to define the sensitivity, specificity and accuracy of case registry matches using non-name-based registries. The AIDS, sexually transmitted disease (STD), and tuberculosis (TB) case registries were matched using all available information to establish the standard. The registries were then matched again using five increasingly less specific criteria to compare sensitivity, specificity and accuracy. The registries were then also transformed into non-name-based codes as if they were the HIV registry and matched again. With name-based registries, sensitivities increased as the matching criteria became less exacting, while the accuracy declined slightly. Specificities remained close to 100% due to the relatively small number of matched cases. Results from matches of non-name-based registry matches were similar to those of the name-based registry matches. Non-name reporting can be used for data matching with acceptable accuracy.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Allogeneic whole-cell vaccine: a phase I/II study in men with hormone-refractory prostate cancer.

OBJECTIVE: To establish the safety and toxicity of an allogeneic human tumour cell vaccine in patients with hormone-refractory prostate cancer, and to determine any biochemical, immunological or clinical response to vaccination. PATIENTS AND METHODS: Sixty patients with hormone-refractory prostate cancer were recruited and randomly allocated into four equal groups. Three cell lines (from a bank of four) were administered initially every 2 weeks and then monthly, in conjunction with the immunostimulant Mycobacterium vaccae (SRL-172), each group receiving a different combination of the four cell lines. The patients' serum prostate-specific antigen (PSA) levels were monitored regularly, and the immune response to the vaccine measured using nonspecific intracellular cytokines and specific humoral and cell-mediated assays. RESULTS: The vaccine was safe and well tolerated with no major side-effects. Whilst several patients had a decline in PSA from the entry level, there was no significant decrease that could be attributed solely to the vaccine. However, the immunological data were more encouraging, with several patients from each arm of the trial having an increase in cytokine production, increases in specific antibodies and evidence of T-cell proliferation in response to the vaccinations. CONCLUSION: The failure of the vaccine to produce a PSA response in the patients in the trial is not surprising considering the stage of the disease. The high PSA levels on entry indicate that the burden of disease was probably high and thus this was an extremely challenging group of patients in which to try and elicit a response through immunotherapy. However, the immunological evidence of a response to the vaccine was encouraging and suggests that further exploration of immunotherapy in less advanced disease may yield more encouraging clinical responses.

Aged↗
PubMed2001

Management of urethritis in health maintenance organization members receiving care at a multispecialty group practice in Massachusetts.

BACKGROUND: Cost containment has led to a concern that health maintenance organization-insured patients presenting with complaints of urethritis may be treated without being tested. GOAL: To determine the proportion of men presenting with symptoms of urethritis who are tested for Chlamydia trachomatis and Neisseria gonorrhoeae. STUDY DESIGN: Reviews were performed on 196 randomly selected patient records with an outpatient visit and a diagnostic code consistent with urethritis between 1995 and 1997. Data were collected on demographics, diagnostic testing, and treatment. RESULTS: Diagnostic testing for C trachomatis and N gonorrhoeae was performed, respectively, in 92.3% and 83.2% of the men presenting at an initial visit with complaints of urethritis. Altogether, 98.2% of the patients who met the Centers for Disease Control criteria for documenting urethritis were tested for C trachomatis and N gonorrhoeae. CONCLUSION: Diagnostic testing for C trachomatis and N gonorrhoeae is nearly universal in this multispecialty group practice setting, facilitating surveillance and public health efforts.

Chlamydia Infections↗
PubMed2000

A filarial nematode-secreted product signals dendritic cells to acquire a phenotype that drives development of Th2 cells.

Although exogeneous "danger" signals such as LPS can activate APC to produce a Th1 response, the nature of events initiating a Th2 response is controversial. We now show that pathogen-derived products have the capacity to induce bone marrow-derived dendritic cell cultures to acquire a phenotype that promotes the differentiation of naive CD4+ T cells toward either a Th1 or Th2 phenotype. Thus, LPS-matured dendritic cells (DC1) promote a Th1 response (increased generation of IFN-gamma and reduced production of IL-4) by Ag-stimulated CD4+ T cells from the DO.11.10 transgenic mouse expressing a TCR specific for an OVA peptide (OVA323-339). In contrast, a phosphorylcholine-containing glycoprotein, ES-62, secreted by the filarial nematode, Acanthocheilonema viteae, which generates a Th2 Ab response in vivo, is found to induce the maturation of dendritic cells (DC2) with the capacity to induce Th2 responses (increased IL-4 and decreased IFN-gamma). In addition, we show that the switch to either Th1 or Th2 responses is not effected by differential regulation through CD80 or CD86 and that a Th2 response is achieved in the presence of IL-12.

Animals↗
PubMed1999

Equine herpesvirus type 1 infects dendritic cells in vitro: stimulation of T lymphocyte proliferation and cytotoxicity by infected dendritic cells.

Equine herpesvirus type 1 (EHV-1) causes respiratory disease, abortion and myeloencephalopathy in horses. As with other herpesviruses, cell-mediated immunity is considered important for both recovery and protection. Although virus-specific T-cell proliferation and cytotoxicity can be detected following in vivo infection, little is known about the role of antigen presenting cells such as dendritic cells (DCs) in these processes. Peripheral blood DCs were shown to express the viral glycoprotein gB perinuclearly following exposure to EHV-1 in vitro, demonstrating EHV-1 replication within them. Co-culture of infected DCs or their supernatants with a susceptible cell line (RK13) demonstrated that EHV-1 infection was productive. In vitro-infected DCs showed cytopathic effects, including loss of viability and syncytial formation. However, they were superior to other antigen presenting cells in stimulating both peripheral blood T-cell proliferation and cytotoxicity. Although ponies which had been intranasally infected with EHV-1 exhibited T-cell proliferation to live virus presented on DCs, the responses began to decline as early as 15 weeks and cease at 22 weeks post-in vivo infection. Cytotoxic responses were not detected 35 weeks after the first intranasal infection but were seen again 7 weeks following a second infection. These findings show that equine DCs, which are infected with EHV-1 in vitro, can stimulate memory T-cell responses but appear unable to circumvent the short-lived memory response found following this infection in vivo.

Animals↗
PubMed1997

Effects of toluidine blue and destaining reagents used in sexual assault examinations on the ability to obtain DNA profiles from postcoital vaginal swabs.

Toluidine blue is an important tool to detect and document genital and perianal injuries following sexual assault. Application of toluidine blue dye and its subsequent removal from unstained areas by means of a destaining reagent, such as diluted acetic acid or a lubricant has been shown to increase the detection rate of posterior fourchette lacerations from 16% to 40% in adult rape victims. Currently, limited information on toluidine blue positive findings in sexually active control groups imposes some limitation on the interpretation of these injuries. Because injuries could otherwise be attributed to improper handling of an examination speculum or the improper insertion of the examining finger, the toluidine blue test should be performed prior to any digital or speculum examination and thus prior to the collection of forensic evidence. For forensic DNA identity testing, it becomes pertinent to determine whether toluidine blue and the destaining reagents used in a sexual assault examination have an adverse effect on the recovery of high molecular weight DNA from postcoital vaginal swabs and thereby have an impact on restriction fragment length polymorphism (RFLP) analysis or PCR-based tests. It is known that some of the lubricants used can have a destructive effect on sperm motility. In order to investigate the potential effects, postcoital vaginal swabs were taken 6 h after sexual intercourse and exposed directly to 1% toluidine blue in aqueous solution, 1-10% acetic acid, and various surgical and vaginal lubricants. Subsequently, the DNA was isolated and DNA identity typing (RFLP and PCR-based) was performed. The results demonstrate, that these reagents have no negative effect on the ability to obtain DNA profiles, either RFLP or PCR-based, from shallow and deep vaginal swabs. The quantity and quality of extractable high molecular weight DNA obtained was comparable with that from uncontaminated postcoital vaginal swabs. RFLP patterns and PCR-based typing results on the D1S80, HUMTH01, TPOX, and CSF1PO loci were consistent with the uncontaminated control swabs and the corresponding whole blood samples of the donors. Therefore, evidentiary material inadvertently contaminated with these reagents can be successfully typed.

Adult↗
PubMed1995

The loss of the sense of reality in incest and child sexual abuse: a psychoanalytic perspective.

This article takes a psychoanalytic perspective on incest and child sexual abuse. It concentrates on what could be called "the loss of the sense of reality" that is experienced by the victim of incest. The position in which a child of five is placed when she is sexually abused by her father is considered; this is followed by detailed material from the analysis of a woman who had an incestuous relationship with her brother. Transference and counter-transference difficulties that arise in work with abused patients are explored. A theoretical explanation of the damaging effects of an incestuous relationship is outlined.

Adolescent↗
PubMed1994

A phase II study of continuous infusion recombinant human granulocyte-macrophage colony-stimulating factor as an adjunct to autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma in first remission.

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) clearly hastens myeloid recovery in patients with relapsed hematologic malignancies undergoing autologous bone marrow transplantation (ABMT). In efforts to further improve neutrophil engraftment and shorten hospital stay in ABMT patients, rhGM-CSF was administered by a potentially more potent route (continuous infusion) to non-Hodgkin's lymphoma (NHL) patients with better BM reserve (first remission). Time to myeloid engraftment was compared with that of NHL patients treated in first remission at our institution on a similar ABMT protocol but without growth factor support (controls). Median neutrophil engraftment (absolute neutrophil count, 500 cells/microL) in first remission patients treated with rhGM-CSF was 14 days, compared with 22 days in controls (P = .0001). Hospital stays were also significantly reduced for rhGM-CSF patients (P = .0003). Platelet engraftment did not differ between the two groups. Persistent fever and generalized serositis were the primary toxicities. rhGM-CSF, delivered by this route, was efficacious but more toxic than 2-hour rhGM-CSF infusions previously reported by other investigators. Future alterations in both dose and schedule may retain comparable efficacy yet diminish toxicity.

Adult↗
PubMed1994

Myelodysplastic syndrome as a late complication following autologous bone marrow transplantation for non-Hodgkin's lymphoma.

PURPOSE: To determine the incidence, natural history, and risk factors associated with myelodysplastic syndrome (MDS) occurring as a late complication following autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma. METHODS: We retrospectively reviewed the charts of all 262 patients who underwent autologous bone marrow transplantation for non-Hodgkin's lymphoma at the Dana-Farber Cancer Institute from 1982 through 1991. Although patients received a variety of treatments before they were eligible for transplant, identical myeloablative therapy (cyclophosphamide 60 mg/kg/d for 2 days plus total-body irradiation twice daily for 3 days) was administered in each case. By collecting data on pretransplant and early posttransplant variables, we attempted to identify risk factors for the development of MDS. RESULTS: The crude overall incidence of posttransplant MDS or acute myeloid leukemia (AML) was 7.6%. The actuarial risk at 6 years was 18% +/- 9%. The median time of onset was 31 months (range, 10 to 101) after transplant or 69 months (range, 27 to 141) after initial treatment for lymphoma. Pretreatment variables predictive for the development of MDS (univariate analysis) included prolonged interval between initial treatment and the transplant procedure (P = .003), increased duration of exposure to chemotherapy (P = .019) or to alkylating agents (P = .045), and use of radiation therapy (P = .032) or pelvic radiation (P = .003) before transplant. CONCLUSION: MDS is a potential complication of autologous bone marrow transplantation for non-Hodgkin's lymphoma; bone marrow stem-cell damage sustained before the transplant may be the most important risk factor.

Adult↗
PubMed1994

Fructose-induced hypertension, hypertriglyceridemia and elevated cytosolic calcium in rats: prevention by deuterium oxide.

We examined the effect of 5% deuterium oxide (D20) in drinking water on systolic blood pressure, platelet cytosolic free calcium, aortic calcium uptake and plasma insulin, glucose and triglycerides in rats with fructose-induced hypertension. Eighteen male Wistar-Kyoto (WKY) rats, age 8 weeks, were divided into 3 groups of 6 animals each. Animals in group I were given water; group II, 8% fructose and group III, 8% fructose + 5% D20 as their drinking water for the next 15 weeks. Systolic blood pressure in the fructose treated rats was significantly higher (p < 0.01) than in animals on water after 2 weeks and remained higher throughout the study. At 15 weeks, systolic blood pressure, platelet cytosolic calcium, aortic calcium uptake and plasma glucose, insulin and triglycerides were significantly higher (p < 0.01) in the fructose treated rats compared with rats from other groups. Deuterium oxide given together with fructose prevented development of high blood pressure and the associated increase in platelet cytosolic calcium, aortic calcium uptake and plasma triglycerides. D20 treatment did not prevent fructose induced increases in plasma insulin and glucose. The parallel increase in systolic blood pressure, cytosolic free calcium, and in vascular calcium uptake suggests that an increased cytosolic free calcium is involved in the pathophysiology of hypertension. D20 prevents this hypertension by normalizing cytosolic free calcium.

Animals↗
PubMed1993

An investigation of the abnormal metabolic status of synovial fluid from patients with rheumatoid arthritis by high field proton nuclear magnetic resonance spectroscopy.

The 1H Hahn spin-echo NMR profiles of rheumatoid synovial fluids have been investigated and compared with those of matched serum samples. In addition to markedly elevated lactate and diminished glucose concentrations, inflammatory synovial fluids contained (i) substantially lower levels of NMR-detectable chylomicron-and very-low-density-lipoprotein-associated triacylglycerols which appear to have a shortened mean chain-length, and (ii) high concentrations of ketone bodies (predominantly 3-D-hydroxybutyrate), relative to those of corresponding paired serum samples. These observations confirm the abnormal metabolic status of the inflamed rheumatoid joint and provide evidence for an increased utilisation of lipids for fuel therein.

3-Hydroxybutyric Acid↗
PubMed1992

Sulphydryl reactivity of the HLA-B27 epitope: accessibility of the free cysteine studied by flow cytometry.

HLA-B27 has an unpaired cysteine on or near its serologically defined spondylitis associated epitope, and it has been argued that its sulphydryl side chain may be chemically reactive. In a previous study it was shown that chemical treatment of HLA-B27 cells with the sulphydryl binding agent p-chloromercuriphenylsulphonic acid (pCMPSA) specifically reduced binding of antibodies to HLA-B27 by up to 80%, as measured in a cellular enzyme linked immunosorbent assay (CELISA). The effect of sulphydryl blockade on intact B27 cells was investigated using flow cytometry. Compared with the CELISA, inhibition required higher concentrations of pCMPSA, and the degree of inhibition produced by a greater than or equal to 30 microM solution of pCMPSA as measured by flow cytometry (median 28.9%) was significantly lower than that measured by CELISA (median 73.6%; p = 1.6 x 10(-6)). Analysis of unfixed, cell surface HLA-B27 by flow cytometry suggests that on most B27 molecules the unpaired sulphydryl site is not available. On the basis of this evidence for modification after translation, a new 'altered self' hypothesis is proposed for the part which HLA-B27 plays in inflammatory disease.

4-Chloromercuribenzenesulfonate↗
PubMed1991

Influence of an intravenous dose of aurothiomalate on the status of low-molecular-mass endogenous metabolites in blood plasma: a proton nuclear magnetic resonance (NMR) study.

The effect of aurothiomalate on the status of a wide range of low-molecular-mass endogenous metabolites in blood plasma obtained from animals treated with an intravenous dose of this second-line agent (150 mg/kg) has been assessed by high field proton Hahn spin-echo NMR spectroscopy. As well as modulating the effective concentrations of NMR-detectable biomolecules, aurothiomalate induces a time-dependent decrease in plasma levels of triacylglycerols with a corresponding elevation in the concentration of the ketone body 3-D-hydroxybutyrate, indicating an increased utilisation of fats for energy in rats treated with this 1:1 gold(I)-thiolate complex. These observations may reflect the toxic side-effects that are associated with aurothiomalate treatment.

3-Hydroxybutyric Acid↗
PubMed1988

Nursing management of the patient with Chlamydia trachomatis infection.

Information on the recognition and management of clinical syndromes commonly caused by Chlamydia should be widely disseminated. Clinicians must be able to make risk assessments on their patients who may have asymptomatic disease. Because chlamydial infections are often undiagnosed, infected patients continue to spread the organisms to their sexual partners and to neonates. Sexual contacts of patients with Chlamydia or gonorrhea should receive treatment regimens effective against both organisms. Patients who are infected with gonorrhea should receive treatment regimens effective against both organisms. Chlamydia culture is the gold standard for detection of the organism. Antigen detection methods have been developed that offer a low-cost alternative to culture, but these tests are not ideal. Chlamydia tests are not a substitute for clinical experience and risk assessment by the nurse practitioner.

Anti-Bacterial Agents↗
PubMed1983

Intracerebral toxoplasmosis in patients with acquired immune deficiency syndrome.

The acquired immune deficiency syndrome (AIDS) is a recently described T-cell deficiency predisposing patients to a spectrum of opportunistic infections. Kaposi's sarcoma, and other neoplasms. It appears primarily among homosexual males and intravenous drug abusers, but is now being observed in other groups as well. The authors describe six adult patients with AIDS who developed intracranial toxoplasmosis. In four patients, diagnosis was made by brain biopsy, and in one by serology. These patients received a 90-day course of therapy with sulfadiazine, pyrimethamine, or both when tolerated, and improved neurologically. In one patient, the brain biopsy was nondiagnostic and the organism was identified at autopsy. On computerized tomographic and pathological follow-up studies the organism appeared to be eradicated by therapy. Early aggressive diagnostic study and prompt institution of therapy are imperative for reversal of neurological deficits. Despite cure of toxoplasmosis, the prognosis in patients with AIDS is poor; the mortality in this series was 67%. Isolation precautions should be taken by those caring for such patients.

Acquired Immunodeficiency Syndrome↗