Biomedical subjects

M Rogers

Publications and source records attributed to M Rogers.

At least 19 recordsLinked to original sources

PubMed2000

Flow cytometric analysis of an immunodeficiency disorder affecting juvenile llamas.

The present study was undertaken to characterize the immune system of llamas and alpacas and establish the basis for an immunodeficiency disorder affecting juvenile llamas. Flow cytometric (FC) analysis of the immune system with a panel of monoclonal antibodies (mAbs) revealed the immune system of llamas and alpacas is similar in leukocyte subset composition to that in ruminants. Peripheral blood mononuclear cells in adults are comprised of surface immunoglobulin (sIg(+)) B-cells (31%+/-8 S.D.), alphabeta T-cells (27%+/-12 S.D.), WC1(+) gammadelta T-cells (16%+/-11 S.D.), and 5-16% monocytes. In contrast to cattle, goats, and sheep, however, the frequency of WC1(+) gammadelta T-cells is not high in juveniles but similar to the frequency in adults. Also, sIg(+) B-cells are present in high concentration in juveniles (43%+/-11 S.D. ). Expression of major histocompatibility class II molecules on resting T-cells was low or absent. Comparative analysis of peripheral blood lymphocyte composition in normal juvenile llamas and llamas presenting with the signs of the juvenile llama immunodeficiency syndrome (JLIDS) revealed the concentration of B-cells is extremely low (1-5%) in affected animals. The findings suggest JLIDS is attributable to an autosomal recessive genetic defect in the development of B-cells.

Animals↗

PubMed2000

Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice.

Each year, an estimated 590,000 infants acquire human immunodeficiency virus type 1 (HIV) infection from their mothers, mostly in developing countries that are unable to implement interventions now standard in the industrialized world. In resource-poor settings, the HIV pandemic has eroded hard-won gains in infant and child survival. Recent clinical trial results from international settings suggest that short-course antiretroviral regimens could significantly reduce perinatal HIV transmission worldwide if research findings could be translated into practice. This article reviews current knowledge of mother-to-child HIV transmission in developing countries, summarizes key findings from the trials, outlines future research requirements, and describes public health challenges of implementing perinatal HIV prevention interventions in resource-poor settings. Public health efforts must also emphasize primary prevention strategies to reduce incident HIV infections among adolescents and women of childbearing age. Successful implementation of available perinatal HIV interventions could substantially improve global child survival.

Adolescent↗

PubMed2000

Modulation of N-type calcium channels translocation in RINm5F insulinoma cells.

An intracellular pool of N-type voltage-operated calcium channels has recently been described in both IMR32 human neuroblastoma and PC12 rat pheochromocytoma cells. These channels were found to be accumulated in subcellular fractions where the chromogranin B-containing secretory granules were also enriched. Upon exocytosis N-type calcium channels were reversibly inserted in the plasma membrane. We have now extended this study to RINm5F rat insulinoma cells, and characterized the parallelism between the 'regulated' secretion of serotonin and the recruitment of surface calcium channels. Exocytosis was stimulated by different means, such as depolarization with high KCl, high Ba(2+)alone or protein kinase C activation; on the other hand exocytosis was inhibited with the non-selective calcium channel antagonist Cd(2+)or with noradrenaline. Stimulated release was always accompanied, with parallel kinetics, by calcium channel recruitment, while inhibition of secretion blocked calcium channel recruitment too. During repetitive depolarizations we revealed a potentiation of [Ca(2+)]()i transients in single Fura-2 loaded RINm5F cells, that was accompanied by an increase in surface VOCCs, suggesting a physiological role for the newly recruited channels. 2000 Academic Press@p$hr

Animals↗

PubMed2000

Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease.

The hematopoietic-specific transmembrane protein tyrosine phosphatase CD45 functions to regulate Src kinases required for T- and B-cell antigen receptor signal transduction. So far, there have been no reports to our knowledge of a human deficiency in a tyrosine-specific phosphatase. Here, we identified a male patient with a deficiency in CD45 due to a large deletion at one allele and a point mutation at the other. The point mutation resulted in the alteration of intervening sequence 13 donor splice site. The patient presented at 2 months of age with severe combined immunodeficiency disease. The population of peripheral blood T lymphocytes was greatly diminished and unresponsive to mitogen stimulation. Despite normal B-lymphocyte numbers, serum immunoglobulin levels decreased with age. Thus, CD45 deficiency in humans results in T- and B-lymphocyte dysfunction.

Antigens, CD↗

PubMed2000

Morphology of lymphatic malformations: a pictorial review.

A pictorial review of the many clinical manifestations of lymphatic malformations is presented, changes to the terminology of lymphatic malformations are reviewed and the 'pros and cons' of relevant investigative techniques are discussed.

Angiokeratoma↗

PubMed2000

Combination therapy with amprenavir, abacavir, and efavirenz in human immunodeficiency virus (HIV)-infected patients failing a protease-inhibitor regimen: pharmacokinetic drug interactions and antiviral activity.

Patients with plasma viral RNA >50,000 copies/mL, despite a protease-inhibitor regimen, received abacavir, amprenavir, and efavirenz to assess efavirenz-amprenavir drug interactions and to evaluate safety and antiviral response. Patients first received amprenavir with abacavir and other nucleoside analogs. Amprenavir levels were measured before and after adding efavirenz. Patients then received a second protease inhibitor. There was evidence of genotypic and phenotypic resistance at study entry. No patient had study drugs discontinued because of toxicity. Efavirenz decreased the steady-state area under the curve, maximum plasma concentration, and minimum plasma concentration of amprenavir by 24%, 33%, and 43%, respectively. Three of 10 patients had >1.5 log10 viral response to abacavir and amprenavir. All 8 patients who added efavirenz had >0.5 log10 decline in viral load, and this response lasted >24 weeks for 3 of the patients. A combination regimen that included abacavir, amprenavir, and efavirenz was well tolerated and had sustained activity in some patients. Concomitant efavirenz therapy decreases amprenavir concentrations.

Adult↗

PubMed2000

Identification of a novel DNA probe for strain typing Mycobacterium bovis by restriction fragment length polymorphism analysis.

Bovine tuberculosis caused by Mycobacterium bovis remains a significant disease of farmed cattle in many countries despite ongoing tuberculosis eradication programs. Molecular typing methods such as restriction fragment length polymorphism (RFLP) analysis and spoligotyping have been used to identify related herd breakdowns in an attempt to identify more precisely the route of infection into cattle herds and to trace the transmission of bovine tuberculosis. A recent geographical survey of Irish M. bovis isolates demonstrated that a significant proportion of isolates ( approximately 20%) exhibit a common strain type, limiting the value of current strain typing methods as an epidemiological tool. We have identified and cloned a region of the M. bovis genome, pUCD, which generates a clear, highly polymorphic banding pattern when used as an RFLP probe on AluI restriction-digested M. bovis genomic DNA and which effectively subdivides this common strain type. When used to type 60 Irish M. bovis isolates, pUCD exhibited greater discriminatory power than the commonly used mycobacterial RFLP probes IS6110, PGRS, and DR and detected an equivalent number of strain types to a combination of these three probes. pUCD also detected significantly more strain types than the spoligotyping technique, while maintaining a high level of concordance between epidemiologically related and unrelated herd breakdowns. The polymorphic element within pUCD remains to be fully characterized, however the potential for this probe to greatly decrease the workload necessary to genotype M. bovis by RFLP analysis is compelling.

Animals↗

PubMed2000

Marriage, monogamy and HIV: a profile of HIV-infected women in south India.

A retrospective study was conducted on 134 HIV-infected females evaluated at an HIV/AIDS centre in south India to characterize their sociodemographics, HIV risk factors and initial clinical presentations. The mean age was 29 years; 81% were housewives; 95% were currently or previously married; 89% reported heterosexual sex as their only HIV risk factor; and 88% reported a history of monogamy. The majority were of reproductive age, thus the potential for vertical transmission of HIV and devastating impacts on families is alarming. Nearly half of these women initially presented asymptomatically implying that partner recruitment can enable early HIV detection. Single partner heterosexual sex with their husband was the only HIV risk factor for the majority of women. HIV prevention and intervention strategies need to focus on married, monogamous Indian women whose self-perception of HIV risk may be low, but whose risk is inextricably linked to the behaviour of their husbands.

Adolescent↗

PubMed2000

Macrocephaly--cutis marmorata telangiectatica congenita: report of five patients and a review of the literature.

Cutis marmorata telangiectatica congenita (CMTC) is a cutaneous disorder often accompanied by additional anomalies, most commonly segmental overgrowth. Recently a clinically discrete condition has been described comprising CMTC and congenital macrocephaly together with pre- and post-natal macrosomia, segmental overgrowth, central nervous system malformations, connective tissue abnormalities and intellectual handicap. We describe the natural history of macrocephaly-CMTC (M-CMTC) syndrome in a further five patients including the oldest reported patient, a 22 year old. The addition of our five patients brings the total number of reported patients to 28 and now makes it possible to more accurately delineate the phenotype and the frequency of clinical manifestations. We add some further clinical associations to those previously described, including anomalies of the growth of hair and teeth, neuronal migration defects, dislocated hips and stridor. We discuss potential genetic mechanisms that might account for the pleiotropic manifestations of this apparently rare segmental overgrowth disorder.

Abnormalities, Multiple↗

PubMed1999

Trends in perinatal transmission of HIV/AIDS in the United States.

CONTEXT: Since 1994, the US Public Health Service (PHS) has recommended routine, voluntary prenatal human immunodeficiency virus (HIV) testing and zidovudine therapy to reduce perinatal HIV transmission. OBJECTIVE: To describe trends in incidence of perinatal AIDS and factors contributing to these trends, particularly the effect of PHS perinatal HIV recommendations. DESIGN, SETTING, AND PARTICIPANTS: Analysis of nationwide AIDS surveillance data and data from HIV-reporting states through June 1998. MAIN OUTCOME MEASURES: Trends in AIDS by year of diagnosis, incidence rates of AIDS and Pneumocystis carinii pneumonia (PCP) among infants younger than 1 year from US natality data for birth cohorts 1988 to 1996; expected number of infants with AIDS from national serosurvey data; and zidovudine use data from selected HIV-reporting states. RESULTS: Perinatal AIDS cases peaked in 1992 and then declined 67% from 1992 through 1997, including an 80% decline in infants and a 66% decline in children aged 1 to 5 years. Rates of AIDS among infants (per 100000 births) declined 69%, from 8.9 in 1992 to 2.8 in 1996 compared with a 17% decline in births to HIV-infected women from 1992 (n = 6990) to 1995 (n = 5797). Among infants, PCP rates per 100000 declined 67% (from 4.5 in 1992 to 1.5 in 1996), similar to the decline in other AIDS conditions. The percentage of perinatally exposed children born from 1993 through 1997 whose mothers were tested for HIV before giving birth increased from 70% to 94%; the percentage who received zidovudine increased from 7% to 91%. CONCLUSIONS: According to these data, substantial declines in AIDS incidence were temporally associated with an increase in zidovudine use to reduce perinatal HIV transmission, demonstrating substantial success in implementing PHS guidelines. Reductions in the numbers of births and effects of therapy in delaying AIDS do not explain the decline.

AIDS-Related Opportunistic Infections↗

PubMed1999

Follow-up evaluation of a phase II prostate cancer vaccine trial.

BACKGROUND: A phase II trial, involving infusions of autologous dendritic cells (DC) and two human histocompatibility antigen (HLA-A2)-specific prostate-specific membrane antigen (PSMA) peptides, was recently completed. Thirty percent of the participants, including subjects with hormone-refractory metastastic disease, and those with suspected local recurrence of prostate cancer, were identified as clinical responders. This report describes the follow-up evaluation of 19 responders in the two study groups. METHODS: After conclusion of the study, study participants were subjected to follow-up evaluations at 6-8-week intervals. Each responder was reevaluated for response status, and duration of response was determined. RESULTS: Subjects were observed for an average of 291 days (metastastic group, group A-2) and 557 days (local recurrence group, group B), which included the treatment and follow-up periods. The average duration of response was 149 days for group A-2, and 187 days for group B. A majority of responders (11/19; 58%) were still responsive at the end of the current follow-up. CONCLUSIONS: The responses observed may be significant and relatively durable. This study suggests that DC-based cancer vaccines in the future may provide an additional therapy for advanced prostate cancer.

Antigens, Surface↗

PubMed1999

GM-CSF as a systemic adjuvant in a phase II prostate cancer vaccine trial.

BACKGROUND: Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF; Leukine [sargramostim], Immunex Corp., Seattle, WA) was administered to a subgroup of 44 patients in a phase II clinical trial for prostate cancer using DC pulsed with HLA-A2-specific prostate-specific membrane antigen (PSMA) peptides. Our purpose was to determine if GM-CSF caused any enhancement of patients' immune responses, including enhancement of clinical response to the DC-peptide treatment. This report compares the clinical responses to DC-peptide infusions with and without systemic GM-CSF treatment. METHODS: GM-CSF was administered by subcutaneous injection at a dose of 75 microg/m2/day for 7 days with each of six infusion cycles. Prefilled syringes were supplied to the patients for self-administration. RESULTS: One complete and 8 partial responders were identified among 44 patients who received GM-CSF, as compared to 2 complete and 17 partial responders among 51 patients who did not receive GM-CSF. For patients who received GM-CSF and were tested by delayed-type hypersensitivity (DTH) skin test, 3 cases of improved immune response were identified, compared to 5 cases of improvement in patients who did not receive GM-CSF. The main GM-CSF side effects reported were local reactions at the site of injection, fatigue, pain, and fever. Most reported side effects were of mild severity, with some cases of moderate severity leading to discontinuation of GM-CSF. CONCLUSIONS: Our results suggest GM-CSF as employed in this trial did not detectably enhance clinical response to DC-peptide infusions, or significantly enhance the measured immune response.

Adjuvants, Immunologic↗

PubMed1999

Phase II prostate cancer vaccine trial: report of a study involving 37 patients with disease recurrence following primary treatment.

BACKGROUND: A phase II trial was conducted to assess the efficacy of infusions of dendritic cells (DC) and two HLA-A2-specific prostate-specific membrane antigen (PSMA) peptides (PSM-P1 and -P2). This report describes the evaluation of 37 subjects admitted with presumed local recurrence of prostate cancer after primary treatment failure. METHODS: All subjects received six infusions of DC pulsed with PSM-P1 and -P2 at 6-week intervals. Clinical monitoring was conducted pre-, during, and post-phase II study. Data included: complete blood count, bone and total alkaline phosphatase, prostate markers, physical examination, performance status, bone scan, ProstaScint scan, and chest X-ray, as well as other assays to monitor cellular and humoral immune responses. RESULTS: One complete and 10 partial responders were identified from this group based on National Prostate Cancer Project criteria, or on a 50% reduction of prostate-specific antigen (PSA), or on a significant resolution in lesions (biopsy-proven when possible) on ProstaScint scan. CONCLUSIONS: About 30% of study participants in this group showed a positive response at the conclusion of the trial. This study suggests that DC-based cancer vaccines may provide an alternative therapy for prostate cancer patients whose primary treatment failed.

Aged↗

PubMed1999

Infusion of dendritic cells pulsed with HLA-A2-specific prostate-specific membrane antigen peptides: a phase II prostate cancer vaccine trial involving patients with hormone-refractory metastatic disease.

BACKGROUND: A phase II trial was conducted to assess the efficacy of infusions of dendritic cells (DC) and two HLA-A2-specific PSMA peptides (PSM-P1 and -P2). This report describes thirty three subjects with hormone-refractory metastatic prostate cancer without prior vaccine therapy history who were evaluated and reported as a group. METHODS: All subjects received six infusions of DC pulsed with PSM-P1 and -P2 at six week intervals. Clinical monitoring was conducted pre-, during, and post- phase II study. Data collected include: complete blood count, bone and total alkaline phosphatase, prostate markers, physical examination, performance status, bone scan, ProstaScint scan, chest x-ray, as well as assays to monitor cellular immune responses. RESULTS: Six partial and two complete responders were identified in the phase II study based on NPCP criteria, plus 50% reduction of prostate-specific antigen (PSA), or resolution in previously measurable lesions on ProstaScint scan. CONCLUSIONS: Over 30% of study participants in this group showed a positive response at the conclusion of the trial. This study suggested that DC-based cancer vaccines may provide an alternative therapy for prostate cancer patients whose disease no longer responds to hormone therapy.

Adult↗

PubMed1999

Phase I study of AG 331, a novel thymidylate synthase inhibitor, in patients with refractory solid tumors.

PURPOSE: This was a phase I study of AG 331 to determine systemic tolerance and pharmacokinetics following single and multiple escalating intravenous doses. METHODS: The study was an open-label phase I trial that was divided into two components. In phase IA (single dose), six dose levels from 12.5 to 225 mg/m2 were administered to 18 patients (3 at each dose level) and serial blood samples were collected for 72 h. Upon achieving satisfactory pharmacologic parameters, the multiple dosing component (phase IB) was initiated. Six dose levels from 50 to 800 mg/m2 per day were administered for 5 consecutive days to 18 patients. Pre- and postdose blood samples were obtained on days 1-4 and serial blood samples were collected over 24 h following dose 5. Nonhematologic and hepatic toxicities were assessed, serum AG 331 concentrations were measured and pharmacokinetic parameters determined. RESULTS: Other than fatigue, no severe toxicities were encountered in phase IA. Liver toxicity was manifested by elevations in transaminase first noted at multiple doses of 200 mg/m2 per day for 5 days. Fever and malaise but no myelosuppression were noted. The mean terminal t1/2 following single doses was significantly shorter than the t1/2 following multiple dosing (6.8 vs 9.9 h) and clearance was significantly faster following single doses than following multiple dosing (81.7 vs 30.4 l/h), but no significant difference in Vd was noted. CONCLUSIONS: The dose-related toxicity profile precludes further clinical development at this time. The pharmacokinetics of AG 331 following single and multiple doses showed significant differences.

Adult↗

PubMed1999

Fixed drug eruptions in children.

To determine the anatomic location and offending drug in fixed drug eruptions (FDE) in children, we performed a 5-year retrospective analysis. Thirty-five children with FDE were evaluated. The most common cause of FDE was the combination drug trimethoprim-sulfamethoxazole.

Adolescent↗

PubMed1999

Periodontal attachment loss in HIV-infected patients is associated with the major histocompatibility complex 8.1 haplotype (HLA-A1,B8,DR3).

Periodontal attachment loss is mediated by overproduction of tumour necrosis factor (TNF) and interleukin (IL)-1, and appears to have a genetic component. The 8.1 major histocompatibility complex (MHC) ancestral haplotype (HLA-A1,B8,TNFA-308(2),DR3) is associated with elevated TNF production and predisposes carriers to several autoimmune/immunopathological disorders, including rapid progression of HIV disease, but not early onset periodontal disease in healthy individuals. Rather a high proportion of subjects with severe periodontal disease carry allele 2 at IL-1A-889 and IL-1B+3953. We predicted that genetic associations may be different or clearer in HIV patients, as they often show elevated production of TNF and IL-1 and periodontal attachment loss. Hence periodontal parameters and IL-1 polymorphisms were assessed in HIV-positive subjects expressing HLA-B8 with or without other markers of the 8.1 haplotype. Of 16 HLA-B8 subjects, 13 demonstrated elevated probing pocket depth and clinical attachment loss. The difference was statistically significant and did not correlate with smoking, age, CD4 T-cell counts, HIV viral load or levels of dental plaque. As TNFA-308 (allele 2) was present in four non-B8 subjects who had minimal attachment loss, it may not mediate the effect of the 8.1 haplotype. Moreover, polymorphisms at IL-1A-889 and IL-1B+3953 did not significantly affect periodontal parameters. Thus a central MHC gene characteristic of the 8.1 haplotype was the clearest determinant of periodontal attachment loss in HIV-infected individuals.

Adult↗

PubMed1999

Seroconversion rates in healthcare workers using a latex agglutination assay after varicella virus vaccination.

OBJECTIVES: To determine the seroconversion rate after varicella immunization of healthcare workers (HCWs) and the effect of seroconversion rate on current cost-based recommendations for universal vaccination. METHODS: A voluntary vaccination program for HCWs was performed at a tertiary-care cancer center in New York City. A commercial latex agglutination assay was used to test postvaccination antibody response. Costs for vaccination and postvaccination serological testing were compared to potential costs of postexposure employee furloughs. RESULTS: Of 263 seronegative HCWs, 96 (36.5%) began the vaccine program. Thirty-nine HCWs received only one dose of vaccine. Seven returned for follow-up antibody testing, of whom 4 were seropositive. Of the 57 HCWs who received two doses, 38 returned for follow-up serology. Thirty-one (81.6%) HCWs were seropositive for varicella-zoster virus antibodies, and seven HCWs (18.4%) remained seronegative. Total cost of vaccination for all 263 seronegative HCWs was estimated and compared to the cost of varicella-related furloughs at our institution. CONCLUSIONS: We found a considerably lower rate of vaccine-induced seroconversion at our hospital compared to that of the published literature. Despite this finding, universal varicella vaccination remained an extremely cost-effective alternative to the furloughing of exposed, seronegative HCWs. Projected hospital savings exceeded $53,000 in the first year after vaccination alone.

Adult↗