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1.
Sci Total Environ ; 921: 171067, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38378055

ABSTRACT

Saltmarsh restoration such as managed realignment (MR) projects often include excavation of simplified tidal creek networks to improve drainage and marsh functioning, but their design is based on limited evidence. This paper compares the morphological evolution of creek networks in current MR projects in the UK with creek networks in natural saltmarshes, in order to provide improved guidance. The evolution of creek networks was monitored for 2-20 years post-breach at 10 MR sites across the UK by semi-automatically extracting 12 morphological creek parameters from lidar. The rates of creek evolution in MR sites are linked to the initial tidal, morphological and sedimentological conditions using principal component analysis, then compared with power law relationships of morphological equilibrium defined from 13 mature natural saltmarshes. MR creeks evolved into larger, more complex, better distributed systems, with a total creek length and volume statistically similar to their natural counterparts. However, the creek volume remains poorly distributed, with a mean distance between creeks ranging from 33 to 101 m versus 5-15 m for natural mature saltmarshes. MR creeks are also clustered around the breach area, leaving the marsh interior poorly drained. MR creek network morphologies remain strongly influenced by the initial creek template, as evidenced by unnaturally straight creeks inherited from former drainage ditches. A combination of external conditions (i.e., tidal range, sediment concentration in the wider estuary) and local conditions (i.e., site elevation, topographical heterogeneity, soil compaction) controls how easily creeks can form within MR sites. This in turn determines the amount of engineering effort required to help achieve reference site conditions. The end goal of creek design is to create MR sites that closely resemble reference site conditions, however the final design is also likely to be affected by a range of practical factors (e.g. engineering/cost) unique to each site and project.

2.
Sci Data ; 9(1): 144, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35365671

ABSTRACT

Coastal wetlands provide crucial ecosystem services including flood protection and carbon storage, but are being lost rapidly worldwide to the combined effects of sea-level rise, erosion and coastal urbanisation. Managed Realignment (MR) aims to mitigate for these losses by restoring reclaimed land to tidal influence. Data of creek evolution is critical to assess the performance of design strategies and improve design and implementation practices. This data descriptor provides a dataset of the horizontal morphological evolution of creek systems from various initial conditions in 10 MR schemes across the UK. Using a semi-automated workflow, morphological creek parameters were extracted from 52 lidar datasets at 1 m horizontal resolution spanning 2 to 20 years post-breach. This constitutes the most comprehensive systematic monitoring of MR creek morphology to date. The dataset will assist future MR design and provide baseline morphological information for ecological and biogeochemical surveying.

3.
Sci Total Environ ; 783: 146880, 2021 Aug 20.
Article in English | MEDLINE | ID: mdl-34088156

ABSTRACT

Resilience is widely seen as an important attribute of coastal systems and, as a concept, is increasingly prominent in policy documents. However, there are conflicting ideas on what constitutes resilience and its operationalisation as an overarching principle of coastal management remains limited. In this paper, we show how resilience to coastal flood and erosion hazard could be measured and applied within policy processes, using England as a case study. We define resilience pragmatically, integrating what is presently a disparate set of policy objectives for coastal areas. Our definition uses the concepts of resistance, recovery and adaptation, to consider how the economic, social and environmental dimensions of coastal systems respond to change. We develop a set of composite indicators for each dimension, grounded empirically with reference to national geospatial datasets. A prototype Coastal Resilience Model (CRM) has been developed, which combines the dimensions and generates a quantitative resilience index. We apply it to England's coastal hazard zone, capturing a range of different stakeholder perspectives using relative indicator weightings. The illustrative results demonstrate the practicality of formalising and quantifying resilience. To re-focus national policy around the stated desire of enhancing resilience to coastal flooding and erosion would require firm commitment from government to monitor progress towards resilience, requiring extension of the present risk-based approach, and a consensus methodology in which multiple (and sometimes conflicting) stakeholder values are explicitly considered. Such a transition may also challenge existing governance arrangements at national and local levels, requiring incentives for coastal managers to engage with and apply this new approach, more departmental integration and inter-agency cooperation. The proposed Coastal Resilience Model, with the tools to support planning and measure progress, has the potential to help enable this transition.

4.
Transbound Emerg Dis ; 65(4): 939-943, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29726097

ABSTRACT

This study diagnosed cutaneous wart lesions excised from three rams from a sheep farm in São Paulo State, Brazil. Histopathologically, these cases were diagnosed as papilloma. The amplification by PCR, sequencing and bioinformatics analysis showed that all the lesions presented DNA sequences of bovine papillomavirus type 2. This is the first report confirming the detection of BPV2 in papilloma warts from ovines.


Subject(s)
Bovine papillomavirus 1/isolation & purification , Papillomavirus Infections/veterinary , Sheep Diseases/virology , Warts/veterinary , Animals , Base Sequence , Bovine papillomavirus 1/genetics , Brazil , DNA, Viral/genetics , Genome, Viral/genetics , Male , Molecular Sequence Data , Papilloma/pathology , Papillomavirus Infections/virology , Polymerase Chain Reaction/veterinary , Sheep , Warts/virology
5.
Transbound. Emerg. Dis. ; 65(4): p. 939-943, 2018.
Article in English | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: but-ib15280

ABSTRACT

This study diagnosed cutaneous wart lesions excised from three rams from a sheep farm in SAo Paulo State, Brazil. Histopathologically, these cases were diagnosed as papilloma. The amplification by PCR, sequencing and bioinformatics analysis showed that all the lesions presented DNA sequences of bovine papillomavirus type 2. This is the first report confirming the detection of BPV2 in papilloma warts from ovines.

6.
Biogeochemistry ; 135(1): 1-34, 2017.
Article in English | MEDLINE | ID: mdl-32009689

ABSTRACT

Continental shelf sediments are globally important for biogeochemical activity. Quantification of shelf-scale stocks and fluxes of carbon and nutrients requires the extrapolation of observations made at limited points in space and time. The procedure for selecting exemplar sites to form the basis of this up-scaling is discussed in relation to a UK-funded research programme investigating biogeochemistry in shelf seas. A three-step selection process is proposed in which (1) a target area representative of UK shelf sediment heterogeneity is selected, (2) the target area is assessed for spatial heterogeneity in sediment and habitat type, bed and water column structure and hydrodynamic forcing, and (3) study sites are selected within this target area encompassing the range of spatial heterogeneity required to address key scientific questions regarding shelf scale biogeochemistry, and minimise confounding variables. This led to the selection of four sites within the Celtic Sea that are significantly different in terms of their sediment, bed structure, and macrofaunal, meiofaunal and microbial community structures and diversity, but have minimal variations in water depth, tidal and wave magnitudes and directions, temperature and salinity. They form the basis of a research cruise programme of observation, sampling and experimentation encompassing the spring bloom cycle. Typical variation in key biogeochemical, sediment, biological and hydrodynamic parameters over a pre to post bloom period are presented, with a discussion of anthropogenic influences in the region. This methodology ensures the best likelihood of site-specific work being useful for up-scaling activities, increasing our understanding of benthic biogeochemistry at the UK-shelf scale.

7.
Vet Rec ; 174(21): 530, 2014 May 24.
Article in English | MEDLINE | ID: mdl-24696442

ABSTRACT

In order to determine the PRNP genotype distribution of the sheep population and to assess the impact of the National Scrapie Plan, a total of 9972 brain samples were collected between January 2012 and April 2013 from sheep sampled under the TSE active surveillance programme in Great Britain. Genotype frequencies observed were ARR/ARQ (29.5 per cent), ARR/ARR (28.6 per cent), ARR/AHQ (10.9 per cent), ARQ/ARQ (9.8 per cent) and AHQ/ARQ (7.2 per cent). Of the remaining possible genotypes, none accounted for more than 5 per cent of the sheep sampled. ARR was the most frequent allele (52.3 per cent), followed by the wild-type ARQ (30 per cent), AHQ (11.3 per cent), VRQ (3.4 per cent) and ARH (3 per cent). There has been a positive but limited effect of the breeding for resistance schemes within Great Britain on the genotype distribution in the sheep national flock. The dissemination of the resistant alleles has proven to have been less noticeable than in the breeding flocks. The risk of atypical scrapie remains very similar to that in 2002. Significant differences were observed in the genotype profiles of the abattoir survey and fallen stock survey samples. It would be advisable to promote best practice among farmers to consolidate the level of genetic resistance in their flocks and to set up a national flock genotype monitoring programme in partnership with the industry.


Subject(s)
Genotype , Scrapie/prevention & control , Sentinel Surveillance/veterinary , Sheep/genetics , Animals , Program Evaluation , Scrapie/genetics , United Kingdom/epidemiology
8.
J Forensic Leg Med ; 20(6): 770-6, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23910879

ABSTRACT

Skeletal remains are excellent sources of information regarding the deceased individual and the taphonomic history of their body. However, the accuracy of this information is governed by our ability to interpret features on the surface of a bone. Little research in this respect has been carried out on remains found in aquatic environments. This study compares damage features created on the surface of modern and archaeological bone found in a seawater environment, to surface features present on unmodified bone, archaeological bone, pathological bone and burned bone. Results show that no similarities with regard to surface pores were identified between submerged modern bone and archaeological, pathological and burned bone. Similarities were seen between submerged and dry archaeological bones. Thus it is argued that the misinterpretation of the taphonomic history of isolated bones recovered from bodies of water should be avoidable in the forensic context.


Subject(s)
Femur/pathology , Fresh Water , Immersion , Microscopy, Electron, Scanning , Seawater , Animals , Burial , Burns/pathology , Forensic Anthropology , Humans
9.
Biomed Res Int ; 2013: 421398, 2013.
Article in English | MEDLINE | ID: mdl-23878806

ABSTRACT

Bovine papillomaviruses (BPVs) are recognized as the causal agents of economical relevant diseases in cattle, associated with the development of tumors in skin and mucosa. The oncogenesis process is mainly associated with different viral oncoprotein expressions, which are involved in cell transformation. The expression and characterization of recombinant viral oncoproteins represent an attractive strategy to obtain biotechnological products as antibodies and potential vaccines, Thus, the aim of this work was to clone and express the BPV-1 and BPV-2 E6 recombinant proteins and perform in silico analysis in order to develop a strategy for the systematic study of other papillomaviruses oncoproteins. The results demonstrated that BPV-1 and BPV-2 E6 recombinant proteins were expressed and purified from bacterial system as well as its in silico analysis was performed in order to explore and predict biological characteristics of these proteins.


Subject(s)
Cloning, Molecular/methods , Oncogene Proteins, Viral/chemistry , Oncogene Proteins, Viral/genetics , Recombinant Proteins/biosynthesis , Recombinant Proteins/chemistry , Sequence Analysis, Protein/methods , Amino Acid Sequence , Molecular Sequence Data , Oncogene Proteins, Viral/biosynthesis , Protein Engineering/methods
11.
J Anim Sci ; 81(6): 1406-13, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12817487

ABSTRACT

Angus bulls (n = 24) were selected for either high or low milk EPD, but with similar growth EPD and mated within location (n = 6) at random to Angus cows. Daughters from these matings were bred to calve first at 2 yr of age to common reference sires across locations. Lactation records for 192 daughters were used to evaluate 12-h milk yield, percentage of milk fat and protein, and weaning weight of offspring. Milk production was measured four times during the lactation at regular intervals within location. Dams were separated from their calves the night before milking and milked with a portable milking machine the next morning to estimate 12-h milk yield. A sample of the milk was collected from each cow and analyzed for percentages of milk fat and protein. Data were analyzed as repeated records of the dam. Fixed effects were location, genetic line of sire, gender of calf within location, and milking period, with postpartum interval used as a covariate. Fixed effects and the random effects of sire of dam nested within line, sire of calf, and year were estimated by REML. Genetic line was an important source of variation for milk yield (P < 0.01) and percentage of milk fat (P = 0.03) but not for percentage of milk protein (P = 0.49). Location was significant for all three milk variables (P < 0.01), but the interactions between line and location were not significant. Gender of calf was significant for milk yield (P = 0.04) but not for percentage of milk fat or protein. Line (P = 0.02), location (P = 0.01), calf gender (P = 0.01), and age at weaning (P = 0.01) were significant sources of variation for weaning weight but the interaction of line and location was not (P = 0.69). The correlation coefficient between the sire's milk EPD and 12-h milk yield was significantly different from zero (r = 0.56). The difference between the least squares means for high and low lines for milk yield was 0.66 kg/12 h and the difference was 15.3 kg for weaning weight. The results indicate that there was not evidence for a genotype by environment interaction in milk production for daughters from divergent sires selected for high or low milk EPD.


Subject(s)
Cattle/physiology , Lactation/genetics , Milk/chemistry , Milk/metabolism , Selection, Genetic , Animals , Cattle/genetics , Fats/analysis , Female , Hybrid Vigor , Lactation/physiology , Male , Milk Proteins/analysis , Random Allocation , Sex Factors
12.
Psychopharmacology (Berl) ; 158(3): 224-9, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11713611

ABSTRACT

RATIONALE: Buspirone is used as a neuroendocrine challenge in which the increase of circulating prolactin is taken as a measure of the sensitivity of central serotonergic (5-HT(1A)) pathways. Interpretation of the test is complicated, however, by the fact that buspirone possesses D(2) antagonist and 5-HT(1A) agonist activity, both of which will result in the release of prolactin. To understand the significance of prolactin secretion in response to buspirone, it is important to measure the differential actions of the two controlling pathways. OBJECTIVE: To characterise the dual action of buspirone in stimulating the secretion of prolactin by blocking the 5-HT(1A) action with the 5-HT1A antagonist action of pindolol. METHODS: Healthy male subjects (n=35) received buspirone (0.5 mg x kg bw(-1) orally) with and without pre-treatment with the 5-HT(1A) receptor antagonist pindolol (40 mg over 2 days, 0.5 mg x kg bw(-1) on test day). Nine subjects underwent two additional trials in which they received a placebo with and without pre-treatment with pindolol. RESULTS: Pindolol alone caused a small but significant reduction (18%) in the tonic release of prolactin. Buspirone alone produced a robust prolactin response which was reduced to approximately half by pindolol pre-treatment. Pindolol pre-treatment also, on average, delayed the onset and peak of the prolactin response. There was wide variation among individuals both in the absolute response to buspirone and in the proportion that could be attributed to the non-serotonergic agonist action of buspirone (22-82% IQ range). CONCLUSIONS: Our results indicate that while serotonergic pathways play a minor role in the tonic release of prolactin, the response to a buspirone challenge alone cannot be used as a simple index of central serotonergic activity. However, if two challenges are carried out, one with buspirone and the other with buspirone plus pindolol, quantitative measures can be made of the sensitivity of both the 5-HT(1A) and the putative D(2) pathways controlling prolactin release.


Subject(s)
Buspirone/pharmacology , Receptors, Serotonin/physiology , Serotonin Receptor Agonists/pharmacology , Adolescent , Adult , Area Under Curve , Cross-Over Studies , Humans , Male , Pindolol/pharmacology , Prolactin/metabolism , Receptors, Serotonin, 5-HT1 , Serotonin Antagonists/pharmacology , Single-Blind Method , Statistics, Nonparametric
13.
J Anim Sci ; 78(10): 2745-53, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11048942

ABSTRACT

Two experiments were conducted to determine effects of oleamide on feed intake and ruminal fatty acids when the oleamide was introduced in the feed vs through a ruminal fistula (Exp. 1) or the oleamide was fed for an extended (9-wk) length of time (Exp. 2). In Exp. 1, four nonlactating Holstein cows, each fitted with a ruminal cannula, were fed four diets in a 4 x 4 Latin square design. Each period lasted 2 wk. Diets consisted of 48% corn silage and 52% concentrate on a DM basis. One diet contained no added fat (control) and a second diet contained 4.2% oleic acid. The remaining two diets were designed to expose cows to 4.2% amide (as oleamide) either through the feed (AF) or by administering oleamide into the rumen (AR) each day through the ruminal cannula. The AF diet reduced DMI similarly to results reported previously for lactating dairy cows and sheep. Intake of the oleic acid diet was intermediate between the control and AF diets. Dry matter intake was reduced by AR similarly to the AF diet. The acetate:propionate ratio in samples of ruminal contents was reduced by oleic acid but not by AF or AR. In Exp. 2, 12 steers were divided into three equal groups of two Angus and two Simmental x Angus crosses, and each group was assigned a diet containing either no added fat (control), 4% oleamide, or 4% high-oleic canola oil. All steers had ad libitum access to feed and water. Dry matter intake by steers fed the canola oil diet was not different from that by steers fed the control diet when averaged over the first 3 wk, the last 3 wk, or over the entire 9-wk study. Oleamide reduced DMI 4 kg/d over the first 3 wk of the study. However, DMI of the oleamide diet consistently increased over the 9-wk study, resulting in wk 7 to 9 DMI that was not different from that of steers fed the control diet. These results show that the reduction in feed intake when oleamide is added to cattle rations can be attributed more to physiological responses than to an undesirable unique taste or odor of the oleamide. In finishing beef steers, the decreased intake induced by oleamide was most severe during the first 1 or 2 wk of feeding but gradually lessened over time until it nearly returned to normal by wk 9.


Subject(s)
Cattle/metabolism , Energy Intake/drug effects , Fatty Acids/metabolism , Food Additives/administration & dosage , Oleic Acids/administration & dosage , Rumen/metabolism , Administration, Oral , Animal Feed , Animals , Body Weight , Female , Food Additives/metabolism , Food Additives/pharmacology , Oleic Acid/pharmacology , Oleic Acids/metabolism , Oleic Acids/pharmacology
14.
Parasitology ; 120 ( Pt 3): 319-27, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10759090

ABSTRACT

Existing models of the basic case reproduction number (R0) for vector-borne diseases assume (i) that the distribution of vectors over the susceptible host species is homogeneous and (ii) that the biting preference for the susceptible host species rather than other potential hosts is a constant. Empirical evidence contradicts both assumptions, with important consequences for disease transmission. In this paper we develop an Ideal Free Distribution (IFD) model of host choice by blood-sucking insects, predicated on the argument that vectors must have evolved to choose the least defensive hosts in order to maximize their feeding success. From a re-analysis of existing data, we demonstrate that the interference constant, m, of the IFD can vary between host species. As a result, the predicted distribution of insects over hosts has 2 desirable and intuitively plausible behaviours: that it is heterogeneous both within and between host species; and that the intensity of heterogeneity varies with host and vector density. When the IFD model is incorporated into R0, the relationship with the vector:host ratio becomes non-linear. If correct, the IFD could add considerable realism to models which seek to predict the effect of these ecological parameters on disease transmission as they vary naturally (e.g. through seasonality in vector density or host population movement) or as a consequence of artificial manipulation (e.g. zooprophylaxis, vector control). It raises the possibility of targeting transmission hot spots with greater accuracy and concomitant reduction in control effort. The robustness of the model to simplifying assumptions is discussed.


Subject(s)
Insect Bites and Stings/veterinary , Insect Vectors/physiology , Insecta/physiology , Models, Biological , Animals , Behavior, Animal , Disease Transmission, Infectious/veterinary , Feeding Behavior , Host-Parasite Interactions , Insect Bites and Stings/epidemiology , Insect Bites and Stings/parasitology , Insect Control , Insect Vectors/parasitology , Insecta/parasitology , Linear Models
15.
J Clin Psychiatry ; 61(2): 129-33, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10732660

ABSTRACT

BACKGROUND: Central nervous system (CNS) adrenergic hyperresponsiveness may be involved in the pathophysiology of posttraumatic stress disorder (PTSD). Two Vietnam combat veterans with PTSD prescribed the centrally active alpha1-adrenergic antagonist prazosin for symptoms of benign prostatic hypertrophy unexpectedly reported elimination of combat trauma nightmares. This observation prompted an open-label feasibility trial of prazosin for combat trauma nightmares in chronic combat-induced PTSD. METHOD: Four consecutively identified combat veterans with chronic DSM-IV PTSD and severe intractable combat trauma nightmares participated in an 8-week open trial of escalating-dose prazosin. Nightmare severity response was rated using the nightmare item of the Clinician Administered PTSD Scale and the Clinical Global Impressions-Change scale. RESULTS: The 2 patients who achieved a daily prazosin dose of at least 5 mg were markedly improved, with complete elimination of trauma nightmares and resumption of normal dreaming. The 2 subjects limited to 2 mg of prazosin to avoid excessive blood pressure reduction were moderately improved with at least 50% reduction in nightmare severity. CONCLUSION: These clinical observations, together with neurobiological evidence for alpha1-adrenergic regulation of CNS neurobiological systems relevant to PTSD, provide rationale for placebo-controlled trials of prazosin for PTSD combat trauma nightmares.


Subject(s)
Adrenergic alpha-Antagonists/therapeutic use , Combat Disorders/drug therapy , Combat Disorders/psychology , Dreams/drug effects , Prazosin/therapeutic use , Aged , Ambulatory Care , Chronic Disease , Combat Disorders/epidemiology , Comorbidity , Drug Administration Schedule , Humans , Male , Middle Aged , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/epidemiology , Psychiatric Status Rating Scales , Severity of Illness Index , Treatment Outcome
17.
Neurology ; 51(1): 101-10, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9674786

ABSTRACT

OBJECTIVE: To determine the number of primary laminin alpha2 gene mutations and to conduct genotype/phenotype correlation in a cohort of laminin alpha2-deficient congenital muscular dystrophy patients. BACKGROUND: Congenital muscular dystrophies (CMD) are a heterogeneous group of muscle disorders characterized by early onset muscular dystrophy and a variable involvement of the CNS. Laminin alpha2 deficiency has been reported in about 40 to 50% of cases of the occidental, classic type of CMD. Laminin alpha2 is a muscle specific isoform of laminin localized to the basal lamina of muscle fibers, where it is thought to interact with myofiber membrane receptor, such as integrins, and possibly dystrophin-associated glycoproteins. METHODS: Seventy-five CMD patients were tested for laminin alpha2 expression by immunofluorescence and immunoblot. The entire 10 kb laminin alpha2 coding sequence of 22 completely laminin alpha2-deficient patients was screened for causative mutations by reverse transcription (RT)-PCR/single strand conformational polymorphisms (SSCP) analysis and protein truncation test (PTT) analysis followed by automatic sequencing of patient cDNA. Clinical data from the laminin alpha2-deficient patients were collected. RESULTS: Thirty laminin alpha2-negative patients were identified (40% of CMD patients tested) and 22 of them were screened for laminin alpha2 mutations. Clinical features of laminin alpha2-deficient patients were similar, with severe floppiness at birth, delay in achievement of motor milestones, and MRI findings of white matter changes with normal intelligence. Loss-of-function mutations were identified in 95% (21/22) of the patients studied. SSCP analysis detected laminin alpha2 gene mutations in about 50% of the mutant chromosomes; PTT successfully identified 75% of the mutations. A two base pair deletion mutation at position 2,096-2,097 bp was present in 23% of the patients analyzed. CONCLUSIONS: Our data suggest that the large majority of laminin alpha2-deficient patients show laminin alpha2 gene mutations.


Subject(s)
Laminin/genetics , Muscular Dystrophies/congenital , Muscular Dystrophies/genetics , Base Sequence , Biopsy , Child , Child, Preschool , DNA Mutational Analysis , Female , Fluorescent Antibody Technique , Gene Deletion , Genotype , Humans , Infant , Laminin/analysis , Male , Molecular Sequence Data , Muscle, Skeletal/chemistry , Muscle, Skeletal/pathology , Muscular Dystrophies/pathology , Mutation , Phenotype , Polymorphism, Genetic
18.
J Rheumatol ; 25(5): 1023-4; author reply 1028-30, 1998 May.
Article in English | MEDLINE | ID: mdl-9598916
19.
Eur J Clin Microbiol Infect Dis ; 15(7): 580-7, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8874076

ABSTRACT

In this multicenter, randomized, double-blind study the activity of polyI:polyC12U administered with zidovudine was evaluated in the treatment of HIV infection. Thirty-six HIV-positive, pre-AIDS individuals (100-500 CD4+ cells/mm3) who had had at least six months of zidovudine therapy received polyI:polyC12U (400 or 700 mg) or placebo twice weekly with zidovudine. PolyI:polyC12U subjects with baseline CD4+ counts > or = 300/mm3 showed a trend towards reduced CD4+ loss versus placebo recipients. PolyI:polyC12U subjects were more likely to exhibit positive delayed-type hypersensitivity responses than placebo recipients. Placebo subjects crossing over to polyI:polyC12U therapy demonstrated improved CD4+ and delayed-type hypersensitivity responses. PolyI:polyC12U subjects with baseline CD4+ counts > or = 300/mm3 were less likely to develop AIDS than similar placebo subjects. PolyI:polyC12U therapy of HIV-positive subjects restored or stabilized immune function as indexed by delayed-type hypersensitivity reactivity and, in individuals with CD4+ counts > 300/mm3, abrogated CD4+ loss and reduced disease progression. PolyI:polyC12U was generally well-tolerated in this zidovudine-treated population. No subject discontinued therapy due to an adverse reaction or aberrant laboratory parameter.


Subject(s)
Antiviral Agents/therapeutic use , HIV Infections/drug therapy , Poly I-C/therapeutic use , Poly U/therapeutic use , Acquired Immunodeficiency Syndrome/etiology , Adult , Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , Antiviral Agents/adverse effects , CD4 Lymphocyte Count , Candida albicans/immunology , Cross-Over Studies , Disease Progression , Double-Blind Method , Drug Hypersensitivity , Drug Therapy, Combination , Female , HIV Core Protein p24/analysis , Humans , Hypersensitivity, Delayed , Male , Middle Aged , Mumps/immunology , Poly I-C/adverse effects , Poly U/adverse effects , RNA, Double-Stranded , Skin Tests , Tetanus/immunology , Trichophyton/immunology , Zidovudine/adverse effects , Zidovudine/therapeutic use
20.
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