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Biomedical subjects

R E Paul

Publications and source records attributed to R E Paul.

At least 19 recordsLinked to original sources
PubMed2002

Fatal non-cardiogenic pulmonary oedema after intravenous non-ionic radiographic contrast.

Life-threatening reactions to radiographic contrast media are rare. We describe a case of fatal non-cardiogenic pulmonary oedema, after use of iopamidol, a widely used, low osmolar, non-ionic, radiographic contrast medium. A woman with a history of bladder tumour who had haematuria was referred for an intravenous urogram. After intravenous injection of 100 mL iopamidol, the woman became short of breath, and a chest radiograph showed severe pulmonary oedema. She was treated but subsequently died. The pathogenesis of contrast-induced, non-cardiogenic pulmonary oedema is unclear, and treatment differs from that for cardiogenic pulmonary oedema.

Aged↗
PubMed2001

Cryofracture electron microscopy of the ookinete pellicle of Plasmodium gallinaceum reveals the existence of novel pores in the alveolar membranes.

The malaria parasite invades the midgut tissue of its mosquito host as a motile form called the ookinete. We have examined the pellicle of the ookinete of Plasmodium gallinaceum by freeze-fracture and quick-freeze, deep-etch electron microscopy. The general organization is analogous to that of invasive stages of other members of Apicomplexa. The pellicle is composed of three membranes: the plasma membrane, and the two linked intermediate and inner membranes, which in the ookinete form one flattened vacuole that is located beneath the plasma membrane. The edges of this vacuole form a longitudinal suture. Beneath the vacuole is found an array of microtubules that are connected to the inner membrane by intramembranous particles. During freeze-fracture, the membranes can split along their hydrophobic planes, thus yielding six fracture faces, each of which displays a characteristic pattern of intramembranous particles. Additionally, we find that the ookinete pellicle differs from all other apicomplexan motile stages by the presence of large pores. These pores are of unknown function, but clearly might constitute a novel pathway for the transport of molecules to and from the cortex, which is independent of the well-described route through the apical micronemal/rhoptry complex. The pores may be the route by which motor proteins or other non micronemal surface proteins are trafficked, such as P25/P28 and SOAP, some of which are implicated in transmission blocking immunity.

Aedes↗
PubMed2000

Sex determination in malaria parasites.

A century ago, W. G. MacCallum identified distinct male and female forms in malaria parasites of both birds and humans. Since then, scientists have been puzzled by the high female-to-male ratios of parasites in Plasmodium infections and by the mechanism of sex determination. The sex ratio of malaria parasites was shown to become progressively more male as conditions that allow motility and subsequent fertilization by the male parasites become adverse. This resulted from an increased immune response against male gametes, which coincides with intense host erythropoietic activity. Natural and artificial induction of erythropoiesis in vertebrate hosts provoked a shift toward male parasite production. This change in parasite sex ratio led to reduced reproductive success in the parasite, which suggests that sex determination is adaptive and is regulated by the hematologic state of the host.

Aedes↗
PubMed2000

Do malaria parasites mate non-randomly in the mosquito midgut?

Polymerase chain reaction (PCR)-based genotyping of oocysts dissected from mosquito midguts has previously been used to investigate overall levels of inbreeding within malaria parasite populations. We present a re-analysis of the population structure of Plasmodium falciparum malaria using diploid genotypes at three antigen-encoding loci in 118 oocysts dissected from 34 mosquitoes. We use these data to ask whether mating is occurring at random within the mosquito midgut, as is generally assumed. We observe a highly significant deficit of heterozygous oocysts within mosquitoes at all three loci, suggesting that fusion of gametes occurs non-randomly in the mosquito gut. A variety of biological explanations, such as interrupted feeding of mosquitoes, positive assortative mating and outcrossing depression, could account for this observation. However, an alternative artefactual explanation--the presence of non-amplifying or null alleles--can account for the observed data equally well, without the need to invoke non-random mating. To evaluate this explanation further, we estimate the frequencies of null alleles within the oocyst population using maximum likelihood, by making the assumption that non-amplifying oocysts at any of the three loci are homozygous for null alleles. Observed levels of visible heterozygotes fit closely with those expected under random mating when non-amplifying oocysts are accounted for. Other lines of evidence also support the artefactual explanation. Overall inbreeding coefficients have been recalculated in the light of this analysis, and may be considerably lower than those estimated previously. In conclusion, we suggest that the deficit of heterozygotes observed is unlikely to indicate non-random mating within the mosquito gut and is better explained by misscoring of heterozygotes as homozygotes.

Alleles↗
PubMed2000

Temporal distribution of the annual nymphal stock of Ixodes ricinus ticks.

The human risk of contracting Lyme disease or other tick borne diseases transmitted by the tick species Ixodes ricinus is broadly linked to the tick nymph density. The study was performed in Rambouillet forest (Yvelines, France), a known focus of Lyme borreliosis, from January 1997 to December 1999. We used a nymph sampling methodology which permitted us to obtain a monthly nymph density index (from 0 to 5). Studying the seasonal nymph and larval activity patterns and estimating the larval developmental duration, we demonstrate the existence of an annual nymphal stock. Secondly, we elucidate how this stock is distributed throughout the year, month by month. Its distribution is principally dependent on two factors: the monthly mean ambient temperature and the proportion of active nymphs which find a host each month. Expected monthly nymph densities derived from a theoretical model describing the temperature-dependent stock distribution gave a good fit to the observed densities, accounting for between 76-86% of the monthly variation in observed nymph densities. Predicting the temporal distribution of nymph activity within a stable Lyme borreliosis focus enables more precise identification of risk periods.

Animals↗
PubMed2000

Erythropoiesis and molecular mechanisms for sexual determination in malaria parasites.

Malaria parasites proliferate asexually within the vertebrate host but must undergo sexual reproduction for transmission to mosquitoes and hence infection of new hosts. The developmental pathways controlling gametocytogenesis are not known, but several protein kinases and other putative signal transduction elements possibly involved in this phenomenon have been found in Plasmodium. Recently, another developmental pathway, that of Plasmodium sex determination (male or female), has been shown to be triggered by erythropoiesis in the host. Rapid progress is being made in our understanding of the molecular basis of mammalian erythropoiesis, revealing kinase pathways that are essential to cellular responses triggered by the hormone erythropoietin. Although the molecular mechanisms whereby this hormone modulates the sex ratio of malaria parasites remain to be elucidated, it probably activates, within the parasite, transduction pathways similar to those found in other eukaryotes. Indeed, enzymes belonging to protein kinase families known to be involved in the response of mammalian cells to erythropoietin (such as the mitogen-activated protein kinases) have been identified in P. falciparum gametocytes. Some of these enzymes differ markedly from their mammalian homologs; therefore, identification of the transduction pathways of the parasite that are responsible for its developmental response to erythropoietin opens the way to the development of transmission-blocking drugs based on kinase inhibitors.

Animals↗
PubMed1999

Aggregation and distribution of strains in microparasites.

Recent research has shown that many parasite populations are made up of a number of epidemiologically distinct strains or genotypes. The implications of strain structure or genetic diversity for parasite population dynamics are still uncertain, partly because there is no coherent framework for the interpretation of field data. Here, we present an analysis of four published data sets for vector-borne microparasite infections where strains or genotypes have been distinguished: serotypes of African horse sickness (AHS) in zebra; types of Nannomonas trypanosomes in tsetse flies; parasite-induced erythrocyte surface antigen (PIESA) based isolates of Plasmodium falciparum malaria in humans, and the merozoite surface protein 2 gene (MSP-2) alleles of P. falciparum in humans and in anopheline mosquitoes. For each data set we consider the distribution of strains or types among hosts and any pairwise associations between strains or types. Where host age data are available we also compare age-prevalence relationships and estimates of the force of infection. Multiple infections of hosts are common and for most data sets infections have an aggregated distribution among hosts with a tendency towards positive associations between certain strains or types. These patterns could result from interactions (facilitation) between strains or types, or they could reflect patterns of contact between hosts and vectors. We use a mathematical model to illustrate the impact of host-vector contact patterns, finding that even if contact is random there may still be significant aggregation in parasite distributions. This effect is enhanced if there is non-random contact or other heterogeneities between hosts, vectors or parasites. In practice, different strains or types also have different forces of infection. We anticipate that aggregated distributions and positive associations between microparasite strains or types will be extremely common.

Adolescent↗
PubMed1999

Application of genetic markers to the identification of recrudescent Plasmodium falciparum infections on the northwestern border of Thailand.

Parasite genotyping by the polymerase chain reaction was used to distinguish recrudescent from newly acquired Plasmodium falciparum infections in a Karen population resident on the northwestern border of Thailand where malaria transmission is low (one infection/person/year). Plasmodium falciparum infections were genotyped for allelic variation in three polymorphic antigen loci, merozoite surface proteins-1 and -2 (MSP-1 and -2) and glutamaterich protein (GLURP), before and after antimalarial drug treatment. Population genotype frequencies were measured to provide the baseline information to calculate the probability of a new infection with a different or the same genotype to the initial pretreatment isolate. Overall, 38% of the infections detected following treatment had an identical genotype before and up to 121 days after treatment. These post-treatment genotypes were considered recrudescent because of the low (< 5%) probability of repeated occurrence by chance in the same patient. This approach allows studies of antimalarial drug treatment to be conducted in areas of low transmission since recrudescences can be distinguished confidently from newly acquired infections.

Alleles↗
PubMed1999

Sex ratio adjustment in Plasmodium gallinaceum.

The sex ratio of the avian malaria parasite, Plasmodium gallinaceum, was examined during the course of infection in its natural host, the chicken. Infections can have two possible outcomes: death of the host resulting from anaemia or self-cure and survival. In lethal infections the sex ratio remained female biased throughout, whereas in self-curing infections, the sex ratio became progressively less female biased. We examined the consequences of altering sex ratio for parasite transmission success using a theoretical fertilisation model and hypothesise that an immune response specifically effective against the male gametes would provide a selective explanation for the observed sex ratio adjustment. Previous studies have demonstrated that there is an efficient anti-gamete antibody response as an infection is cleared by the host. We performed in vitro mosquito infection studies comparing mosquito infection rates with naive serum replacement and showed that decomplemented serum from curing infections is transmission blocking, whereas serum from lethal infections is not. We discuss aspects of the malaria parasite-host interaction which might provide the selective pressure for such observed sex ratio adjustment.

Animals↗
PubMed1998

Mating Patterns of Plasmodium falciparum.

Recent empirical data have enabled a more informed debate over the extent of clonality in Plasmodium falciparum populations. Oocyst heterozygosity data reveal that the mating structure of malaria populations varies according to the transmission intensity. This finding provides a more detailed picture of the malaria mating structure than previous conclusions, which were based on indirect measures of population mating structure, ie. linkage disequilibrium analyses. In this article, Ric Paul and Karen Day discuss aspects of the genetic structure of malaria populations as evidenced by oocyst heterozygosity and linkage disequilibrium data. They address the difficulties of performing genetic analyses of malaria parasite population structure inherent in parasite sampling, why two identical parasites are rarely observed in the field and how features of the epidemiology determine parasite population structure.

Journal Article↗
PubMed1998

Transmission intensity and Plasmodium falciparum diversity on the northwestern border of Thailand.

Genetic analysis of the number of Plasmodium falciparum genotypes per infected person in regions of holoendemic and hyperendemic malaria suggest that in areas of lower transmission intensity, significantly fewer parasite genotypes per infected person should be found. A predominance of single clone infections in the human population could generate the controversial clonal population structure proposed for P. falciparum by Tibayrenc and others. Characterization of P. falciparum from individuals on the Thai-Burmese border, an area of hypoendemic transmission, revealed a higher number of genotypes per infected person than that predicted. Possible reasons for this observation are discussed, with particular attention paid to human migration and multidrug resistance.

Adolescent↗
PubMed1996

The effect of local anesthesia with vasoconstrictor on gingival blood flow during Le Fort I osteotomy.

PURPOSE: In earlier studies, it has been documented that maxillary gingival blood flow (GBF) decreased significantly during the intraoperative course of a Le Fort I osteotomy. It was not clear, however, whether the observed decrease in GBF was caused by the osteotomy or by the use of local anesthetic with vasoconstrictor (LA + V). The purpose of this study was to measure the effect of LA + V on GBF during Le Fort I osteotomy using laser Doppler flowmetry (LDF). PATIENTS AND METHODS: Using a randomized clinical trial study design, patients undergoing Le Fort I osteotomy were assigned to either a treatment (group 1, LA + V used) or a control group (group 2, LA + V not used). The predictor variable was group assignment (LV + V used or not used). The outcome variable was mean maxillary GBF. Maxillary GBF was recorded at predetermined times during the operation. Other study variables included age, sex, single- or double-jaw surgery, estimated blood loss, direction and magnitude of maxillary movements, temperature, pulse, mean blood pressure, O2 saturation, and duration of operation. RESULTS: There were 19 patients in group 1 (LA + V used) and 15 patients in group 2 (LA + V not used). In both groups, mean maxillary GBF decreased significantly during the operation (group 1, 33.3 +/- 13.1 to 16.9 +/- 16.1 mL/ min/100 g tissue, P = .015; and group 2, 48.2 +/- 17.1 to 15.5 +/- 7.6 mL/min/100 g tissue, P = .001). The decrease in GBF occurred much earlier in group 1. By an average of 2.3 hours into the operation, the mean GBF was equivalent in both study groups (group 1, 10.6 +/- 8.6, and group 2, 13.1 +/- 9.4 mL/min/100 g tissue, P = .44). CONCLUSIONS: The results of this study confirm earlier findings that mean maxillary GBF decreases significantly during the intraoperative course of a Le Fort I osteotomy. In addition, LA + V significantly affects GBF during the early phase of the operation. Its effect, however, dissipates between the time of soft tissue dissection and maxillary downfracture.

Adult↗
PubMed1995

Mating patterns in malaria parasite populations of Papua New Guinea.

Description of the genetic structure of malaria parasite populations is central to an understanding of the spread of multiple-locus drug and vaccine resistance. The Plasmodium falciparum mating patterns from madang, Papua New Guinea, where intense transmission of malaria occurs, are described here. A high degree of inbreeding occurs in the absence of detectable linkage disequilibrium. This contrasts with other studies, indicating that the genetic structure of malaria parasite populations is neither clonal nor panmictic but will vary according to the transmission characteristics of the region.

Alleles↗
PubMed1989

Clinical pharmacology of chronic orofacial pain medications.

Pharmacologic intervention with nontraditional analgesics such as antidepressants, anticonvulsants, and ergot alkaloids, is often useful in the management of chronic pain disorders, including those in the orofacial region. The side effects of these drugs are different and often more severe than the analgesics commonly prescribed in dental practices and their prescription by those without advanced training in the area of chronic pain management is not recommended. This article will review the mechanism of action, efficacy, and toxicity of some of the more commonly prescribed chronic pain medications.

Analgesics↗
PubMed1985

Malabsorption in Marfan (Ehlers-Danlos) syndrome.

A patient with somatic features of both Marfan and Ehlers-Danlos syndromes presented with severe intestinal malabsorption. Functional intestinal abnormalities were thought to be due to bacterial overgrowth associated with small intestinal hypomotility and giant jejunal diverticula. The structural intestinal defects are presumed to be the result of defective collagen synthesis in these hereditary connective tissue disorders.

Adult↗
PubMed1984

Hypersensitivity to electrical stimulation of auditory nuclei follows hearing loss in cats.

The purpose of the study was to determine if permanent, sound-induced hearing loss altered behaviorally measured thresholds for the detection of electrical stimulation applied to auditory nuclei. Electrodes were placed in cochlear nucleus and inferior colliculus in four cats. Behaviorally measured thresholds for the detection of brief trains of electrical pulses were determined before and after a 48 h exposure to a 1 kHz tone of approximately 110 dB SPL. The mean decrease in electrical stimulation threshold as a result of the sound exposure was 10.4 dB. The ongoing electrical activity (in microV, rms) recorded from the electrodes showed a mean 2.2 dB decrease after the sound exposure. In some electrodes, there was partial recovery towards pre-exposure levels for stimulation threshold and for ongoing activity, but typically, the changes persisted until the animals were terminated 30 days later. The magnitudes of the decreases in stimulation threshold and background activity proved not to be highly correlated. The permanent auditory threshold shift across all cats and all frequencies was 19 dB. This mild hearing loss produced a marked alteration in certain characteristics of the central auditory mechanisms.

Animals↗
PubMed1983

Chronic erosive gastritis--a recently recognized disorder.

We have reviewed the clinical manifestations, endoscopic findings, pathology, and upper gastrointestinal x-rays in 10 patients with chronic erosive gastritis, a disorder that was rarely recognized before the use of double-contrast upper gastrointestinal radiology and endoscopy. The characteristic x-ray appearance is that of a series of 3 to 11-mm nodules, some with central collections of barium, that are distributed along rugal folds and usually extend into the antrum. The endoscopic appearance is similar: small erythematous nodules with shallow central erosions. The pathology differs from that seen in peptic ulcer disease. There are few polymorphonuclear leukocytes and a predominance of plasma cells in the inflammatory infiltrate. Seven of our patients presented with epigastric pain similar to that of peptic ulcer disease; four of these also had anorexia and weight loss. In two other patients anorexia and weight loss were the only symptoms. One patient was asymptomatic. All nine symptomatic patients responded to antacid treatment. However, repeat x-rays demonstrated persistence of the nodules, although the central erosions usually disappeared. The etiology is unknown. Chronic erosive gastritis appears to be a distinct entity different from peptic ulcer disease.

Adult↗