Search PubMed⌕ Search

Biomedical subjects

C Holland

Publications and source records attributed to C Holland.

At least 37 records · Page 2Linked to original sources
PubMed1998

Long-term efficacy and immune responses following immunization with the RTS,S malaria vaccine.

The malaria sporozoite vaccine candidate RTS,S, formulated with an oil-in-water emulsion plus the immunostimulants monophosphoryl lipid A and the saponin derivative QS21 (vaccine 3), recently showed superior efficacy over two other experimental formulations. Immunized volunteers were followed to determine the duration of protective immune responses. Antibody levels decreased to between one-third and one-half of peak values 6 months after the last dose of vaccine. T cell proliferation and interferon-gamma production in vitro were observed in response to RTS,S or hepatitis B surface antigen. Seven previously protected volunteers received sporozoite challenge, and 2 remained protected (1/1 for vaccine 1, 0/1 for vaccine 2, and 1/5 for vaccine 3). The prepatent period was 10.8 days for the control group and 13.2 days for the vaccinees (P < .01). Immune responses did not correlate with protection. Further optimization in vaccine composition and/or immunization schedule will be required to induce longer-lasting protective immunity.

Adolescent↗
PubMed1998

Passive transfer of growth-inhibitory antibodies raised against yeast-expressed recombinant Plasmodium falciparum merozoite surface protein-1(19).

Purified rabbit immunoglobulin raised against yeast-expressed recombinant FVO or 3D7 Plasmodium falciparum merozoite surface protein-1 (MSP-1) 19k-D C terminal fragment (MSP-1(19)) was transfused into malaria-naive Aotus nancymai monkeys that were immediately challenged with FVO asexual stage malaria parasites. Control monkeys received rabbit immunoglobulin raised against the sexual stage antigen Pfs25 or Aotus hyperimmune serum obtained from monkeys immunized by P. falciparum infection and drug cure. Passive transfer of rabbit anti-MSP-1(19) failed to protect against homologous or heterologous challenge and, when compared with negative controls, there were no differences in prepatent periods or time to treatment. Interestingly, rabbit anti-MSP-1(19), but not anti-Pfs25, immunoglobulin, and immune monkey serum prevented the development of antibodies directed against MSP-1(19) fragment by infected monkeys, indicating that the antibodies were reactive with native MSP-1(19) antigen in vivo. The prepatent period and time to treatment was greatly delayed in the two monkeys that received Aotus immune serum, both of which developed a chronic intermittent low level infection. In vitro parasite growth inhibition assays (GIAs) confirmed the presence of inhibitory activity (40% maximum inhibition) in concentrated anti-MSP-1(19) immunoglobulin (4.8 mg/ml), but the peak concentrations we achieved in vivo (1 mg/ml) were not inhibitory in vitro. Subinhibitory levels of anti-MSP-1(19) antibodies achieved by passive transfer were not protective against P. falciparum challenge.

Animals↗
PubMed1997

Paroxetine and pindolol: a randomized trial of serotonergic autoreceptor blockade in the reduction of antidepressant latency.

A double-blind, randomized, placebo-controlled, parallel group study was performed in 80 adult outpatients meeting ICD-10 criteria for major depression and with a Montgomery-Asberg Depression Rating Scale (MADRS) score of at least 18 at baseline. All patients received paroxetine (20 mg once a day) plus either pindolol (2.5 mg three times a day) or matching placebo for 6 weeks. Analysis of the day 14 MADRS scores on an intent-to-treat basis revealed a treatment-by-centre interaction, with a significant effect of pindolol being demonstrable at only one centre. At this centre, 25% of the paroxetine plus pindolol group and 0% of the paroxetine plus placebo group showed a decrease of at least 50% from baseline MADRS by day 4 (p < 0.05). At day 14, the proportions were 73% and 7%, respectively (p < 0.001). Analysis of covariance on a "perprotocol" population demonstrated a significant accelerator effect of pindolol at days 4 and 7 in the absence of a treatment-by-centre interaction, but a centre effect was apparent at later time-points. The results suggest that the latency of antidepressant action can be reduced with pindolol augmentation. A large multicentre study is in progress to investigate this effect further.

Adrenergic beta-Antagonists↗
PubMed1995

Population biology of Pomphorhynchus laevis in brown trout from two lakes in the west of Ireland.

Since Ireland is the only country in which Pomphorhynchus laevis (Acanthocephala) uses brown trout (Salmo trutta) as its preferred definitive host, the population biology of the parasite in this host was investigated thus enabling a comparison to be made with data collected on P. laevis from other hosts, particularly the cyprinids, chub and barbel. Over a period of 12 months, 549 brown trout were caught from two lakes, Lough Feeagh and Bunaveela Lake, in the Burrishoole River system, Co. Mayo, Ireland. The parasite component community was dominated by a single species, P. laevis. Fifty eight percent of the trout sample were infected with the acanthocephalan and the mean abundance (+/- SD) was 3.1 +/- 5.1 The relationships between the prevalence and abundance of P. laevis and season and site of host capture and host age and sex were explored. As single factors one of these parameters emerged as significant contributions to changes in parasite abundance although some interaction terms proved to the significant. A random sample of over 700 P. laevis parasites were subjected to further investigation and their size, position in the intestine and maturity status are described. Parasites attained an average weight of 7 mg and occupied the posteriad positions within the fish intestine (77%). Parasites from this sample of Irish brown trout attained a similar average size to those found in chub and barbel from England. 42.3% of the total parasites examined contained ovarian balls only and 17% contained fully mature acanthors. Therefore only a moderate proportion of female worms contained mature acanthors in these trout whereas the majority of worms recovered from a sample of chub were gravid. Utilizing a logistic regression model, parasite size, season, and site of host capture emerged as particularly significant factors which contribute to whether a parasite contains mature eggs.

Acanthocephala↗
PubMed1995

Metazoan parasite community structure in brown trout from two lakes in western Ireland.

A total of 549 brown trout were caught from two lakes, Lough Feeagh and Bunaveela Lake, in the Burrishoole system, Co. Mayo, Ireland. Seven species of metazoan parasite were detected but only four species occurred in > or = 10% of the sample. The parasite community of the trout was dominated by a single species, Pomphorhynchus laevis, with a prevalence if 58%. Only one allogenic helminth species was recorded from the trout, Diphyllobothrium ditremum, with the community mainly comprising autogenic species. Few differences were found between the two lakes, although the larger lake, Lough Feeagh, did contain some trout which harboured more parasite species and had, on average, fish with higher numbers of individual parasites. Measures of species richness and diversity were very low, indicating an impoverished helminth community with little potential for interspecific interactions. Host age was found to significantly influence these indices of infracommunity structure.

Animals↗
PubMed1994

Paternity by cardiac transplant recipients.

To assess whether children fathered by cardiac transplant recipients are at high risk of teratogenicity, cardiac transplant centers listed with the International Society for Heart and Lung Transplantation were surveyed. Paternities after transplantation by heart (n = 35) and heart-lung (n = 1) allograft recipients have resulted in 42 pregnancies (children's age 3.3 +/- 0.3 years). The fathers' age at conception was < 45 years in 40 (95%) and > 45 years in 2 (5%). Most fathers (86%) were enjoying an active and healthy lifestyle at the time of conception; one (2%) was on dialysis and listed for kidney transplantation due to nephrotic syndrome, 1 (2%) had asthma, 4 (10%) had allograft coronary disease (1 died while waiting for second heart transplant when the child was 2 months old), and 2 (5%) were retransplanted after the pregnancies. Immunosuppressive regimens were reported for 37 paternities; drug protocols at the time of conception were as follows: 25 (60%) CsA/prednisone/AZA, 6 (14%) CsA/prednisone, 4 (10%) CsA/AZA, and 2 (5%) AZA/prednisone. Twenty-six (62%) had received treatment for rejection episodes before conception; seven (17%) had received treatment for rejections since conception. Of the 42 children fathered by these recipients, 3 (7%) were preterm, 1 (2%) had a cleft palate and lip that have subsequently been corrected, 1 (2%) died from interruption of umbilical cord circulation at 24 weeks, and 1 (2%) whose father had familial cardiomyopathy was born with a cardiomyopathy that improved with time. Although the numbers are small, the available data suggest that paternity by cardiac transplant recipients may be safe.

Adult↗
PubMed1994

Plasmodium falciparum: further characterization of a functionally active region of the merozoite invasion ligand EBA-175.

A 42 amino acid peptide, Pf EBA-175 (1062-1103), also called EBA-peptide 4 of the 175-kDa Plasmodium falciparum sialic acid binding protein, a putative merozoite invasion ligand, has been shown to be a target of parasite growth inhibitory antibodies. We expressed and purified a recombinant protein, NS1-Pf EBA-175 (946-1133) which included the 42 amino acid peptide, and compared antibodies induced by immunization with the protein to antibodies raised against the 42 amino acid peptide. Sera from rabbits immunized with the recombinant protein and the synthetic peptide immunoprecipitated authentic EBA-175, and had comparable ELISA titers against peptide Pf EBA-175 (1062-1103). However, IFAT titers against infected erythrocytes and growth inhibitory activity were substantially higher in sera from animals immunized with the 42 amino acid synthetic peptide. Epitope mapping of the 42 amino acid peptide identified a 19 amino acid peptide, Pf EBA-175 (1069-1087), which blocked the ability of antibodies against the 42 amino acid peptide to (1) immunoprecipitate EBA-175, (2) bind to the 42 amino acid peptide in an ELISA, and (3) recognize infected parasites in an IFAT. Sera from rabbits immunized with the 19 amino acid peptide conjugated to KLH had excellent parasite growth inhibitory activity (at 1:5 serum dilution, 49.9 +/- 7.4%, mean +/- SD of three separate assays), but the activity was lower in each of the three assays than that of sera from rabbits immunized with the 42 amino acid peptide (67.8 +/- 24.8%). These data indicate that the activity of antibodies raised against the linear 42 amino acid peptide, Pf EBA-175 (1062-1103) are primarily, if not exclusively, directed against 19 of the 42 amino acids, and identify this region of Pf EBA 175 as a target for vaccine development.

Amino Acid Sequence↗
PubMed1994

Do clinicians tell each other enough? An analysis of referral communications in two specialties.

Referral letters and replies are an important vehicle for conveying information about patients and for creating and sustaining professional relationships. Studies of communication between hospital specialists and GPs, however, suggest that improvements could be made to the content of letters. In this study, which is part of a larger study of referral expectations, a sample of 39 letters to and from the ENT and Rheumatology departments at Sunderland Royal Infirmary was analysed to find out what objectives were being achieved through the correspondence between consultants and GPs. An analytical framework of letter content was derived from a review of 25 letters to and from each specialty and from a separate study of doctors' opinions of letter content conducted by two of the authors. Doctors recruited to the present study were involved in devising a weighted scoring system for letter content. Analysis showed that the letters accomplish the basic objective of transferring clinical and administrative information. They were less likely to contain items of a socio-psychological type. There was very little difference in the standardized letter scores between the two specialties. While the level of detail recorded in this sample may be adequate for straightforward referrals, there are indications that clinicians' letters are frequently not addressing nonclinical matters that can be a complicating factor in a proportion (perhaps a fifth) of referrals. This may be a possible topic for audit in multidisciplinary groups.

Communication↗
PubMed1994

Correlation between cellular rejection of cardiac allografts and quantitative changes among T-cell subsets identified by V beta epitope expression.

BACKGROUND: Cellular rejection of an allograft is mediated in part by peripheral blood T cells. We tested the hypothesis that quantitative changes in T-cell subsets can be detected in the peripheral blood and that these changes correlate with rejection. METHODS AND RESULTS: T-cell subset analysis was performed by flow cytometry using monoclonal antibodies recognizing six isotypic epitopes of the T-cell receptor beta-chain variable (V) region. These analyses were done at 7-day (mean) time intervals. Fluctuations within a given subset were determined by dividing the number of positive cells observed by the number of positive cells found on the previous analysis. For healthy volunteers observed over a period of 30 days, 119 of 120 subset ratios (99.2%) fell between 0.5 and 2.0. For patients, 57 of 240 subset ratios (23.8%) fell outside of this range (P < .004, chi 2). The occurrence of the abnormal ratios coincided more closely with cellular rejection (mean +/- SD, 7.7 +/- 6.2 days from a positive biopsy; median, 5 days; range, 0 to 28 days) than did the occurrence of normal subset ratios (mean +/- SD, 14.4 +/- 10.9 days from a positive biopsy; median, 11 days; range, 0 to 44 days; P < .005 by Mann-Whitney U test). Regression analysis confirmed a significant (P < .001, R = .91) temporal association between cellular rejection and abnormal subset fluctuations. No correlation was found between abnormal subset ratios and either vascular rejection or use of high-dose prednisone. CONCLUSIONS: T-cell subset measurement may be a method of noninvasive monitoring of cellular rejection after transplantation and may provide insights into the physiology of graft rejection with the potential for the development of more specific immunosuppressive therapy.

Adult↗
PubMed1994

The effects of azidothymidine therapy on pseudocholinesterase concentrations in asymptomatic HIV-positive patients.

The purpose of this study was to determine if a correlation exists between long-term azidothymidine (AZT) therapy and low pseudocholinesterase concentrations in patients who are infected with the human immunodeficiency virus (HIV). A pilot study was conducted of 10 patients infected with HIV, 5 of whom were receiving AZT. Laboratory tests, including complete blood count (CBC), liver function tests, helper/inducer T lymphocyte numbers (CD4), serum dibucaine numbers, and serum pseudocholinesterase concentrations were examined. Control and study subjects both exhibited normal dibucaine numbers, but the pseudocholinesterase concentrations were significantly lower in the group that was not receiving AZT relative to the AZT treatment group. However, only two patients, neither of whom were receiving AZT, demonstrated low or borderline low pseudocholinesterase concentrations according to laboratory criteria. It is possible that pseudocholinesterase synthesis is significantly inhibited by the HIV disease process and that treatment with AZT partly reverses the inhibition. Associated variables contributing to low pseudocholinesterase concentrations in the HIV-positive patient are explored.

Adult↗
PubMed1993

Increased frequency of alloantigen-reactive helper T lymphocytes is associated with human cardiac allograft rejection.

Endomyocardial biopsy (EMB) is the standard method of monitoring heart transplant recipients for the development of allograft rejection. To date, noninvasive methods to detect cardiac allograft rejection have lacked adequate sensitivity and specificity for wide clinical application. In this study, limiting dilution analysis (LDA) was used to quantitate the number of donor alloantigen-reactive helper T lymphocytes (HTLs) in the peripheral blood of cardiac transplant recipients. Cadaveric donor splenocytes were cryopreserved, providing a source of donor alloantigenic stimulation for these assays. Peripheral blood mononuclear cells were harvested from cardiac transplant recipients before transplantation and at the time of EMB. LDA of donor-reactive HTLs was conducted simultaneously on all time points to minimize experimental variation, and these data were related to EMB scores. Frequencies of donor-reactive HTLs in pretransplant samples were highly variable, ranging from 1/1381 to < 1/200,000, and correlated poorly with the degree of HLA disparity. During episodes of moderate rejection, donor-specific HTL frequencies increased an average of 6 times their post-transplant baseline frequency. Additionally, 10-fold increases in HTL frequencies were seen preceding EMB-diagnosed rejection in several individuals. These data indicate that episodes of allograft rejection are associated with increases in the number of circulating donor-reactive HTL which are frequently detected before the development of histologically defined rejection. Thus, monitoring HTL frequencies may serve as a non-invasive method for detecting and predicting cardiac allograft rejection. Furthermore, this assay may provide a valuable means of assessing the in vivo efficacy of various immunosuppressive therapies.

Graft Rejection↗
PubMed1992

A survey of the intestinal helminths of refugees in Juba, Sudan.

A parasitological survey of refugees based in Juba, Sudan, involving 241 faecal samples, revealed that 66% of the population harboured intestinal helminths. The most commonly found infection was hookworm (36%), followed by Schistosoma mansoni (26%), Strongyloides stercoralis (20%), Hymenolepis nana (11%), Ascaris lumbricoides (1.2%), Trichuris trichiura (0.8%) and Taenia sp. (0.4%). Many of the specimens (42%) harboured a single infection, 21% had double, 2% triple and 1% quadruple infections. Parasite prevalences and intensities were analysed in relation to age, sex, religion and occupation: females (70%) were found to be more infected than males (64%); Muslims (50%) were less infected than Christians (68%) and agriculturalists (90%) were the most infected occupational group.

Adolescent↗
PubMed1991

Families, parks, gardens and toxocariasis.

Toxocara canis antibody titres were measured in members of 30 families. 73/140 (52.1%) family members were seropositive for T. canis at a dilution greater than or equal to 1:50 and 11 (7.8%) had reciprocal titres greater than or equal to 800. Toxocara ova were sought (a) in relation to the 30 families and (b) in the community. No toxocara ova were found in household dust samples. 38% of family gardens contained toxocara ova while 6% of soil samples from public parks and open spaces around housing estates were positive. None of the faecal specimens from pet dogs were positive for toxocara ova as compared to 6.2% of stray dogs. 5.3% of canine faecal samples from the streets contained toxocara ova. In this study household garden soil was a potentially greater source of toxocara infection than soil in public parks and open spaces.

Adolescent↗