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Biomedical subjects

P A Wilson

Publications and source records attributed to P A Wilson.

At least 19 recordsLinked to original sources

A technique for skin application of exact doses of Nippostrongylus brasiliensis to rats.

Conventional methods for percutaneous infection of rats using third-stage juveniles of Nippostrongylus brasiliensis which have been artificially stimulated to exsheath lead to highly variable, and relatively poor, establishment in the intestine. A new system has been developed in which larvae applied to the skin still remain partially sheathed, as they would be in nature. Cultures of the freeliving stages of the parasite contain an annulus of clear, colourless polythene film to which some of the third-stage juveniles attach. Rats are infected with an individually counted, exact dose applied to the skin on polythene. Using this technique ('EDT20Nb'), consistently high values for the mean proportion of the dose that becomes established (pf) have been obtained, along with a variance well below the normally accepted level (pf = 0.784 +/- 0.015 from a total of 73 rats in 12 separate assays). In particular, the added component of variance between assays in this study was insignificant, so that the probability of quantitative agreement in replicate experiments based on the method is high. It is recommended for an experimental design in which small numbers of parasites can be used.

Analysis of Variance

A basis to extend the proof of migration routes of immature parasites inside hosts: estimated time of arrival of Nippostrongylus brasiliensis and Strongyloides ratti in the gut of the rat.

The time taken for larvae of Nippostrongylus brasiliensis and a homogonic strain of Strongyloides ratti to complete their migration from the skin surface to the small intestine of the rat was estimated by a new method in which a mirror image of arrival times was created by counting mature parasites at day 8 (N. brasiliensis) or day 5 (S. ratti) in the intestines of rats that had received a single pulse of morantel tartrate by stomach tube at different times starting 10 h after skin application of exact doses of infective larvae. It was confirmed that the effect of the drug was confined to parasites in the gut, so that the kinetics of migration were unperturbed. The persistence of the anthelmintic effect in the gut was shown by independent assays to be less than 8 h for both species. The time-course of arrival calculated from drug pulse data corrected for persistent effects was compared with direct counts of larvae arriving in the intestines of rats not dosed with anthelmintic. Both methods agreed in all respects for N. brasiliensis, whereas the estimates for direct counts of S. ratti, lagged 15-17 h behind those from drug-treated rats. In the discussion it is argued that the anthelmintic method provides a more correct picture for S. ratti and, on this basis, rates and synchrony of migration of the two species are compared. The role of these data as part of a proof of migration routes is explained.

Animals

An extended proof of migration routes of immature parasites inside hosts: pathways of Nippostrongylus brasiliensis and Strongyloides ratti in the rat are mutually exclusive.

Rigorous proofs applicable to the routes of migration of Strongyloides ratti and Nippostrongylus brasiliensis skin-penetrating juveniles inside the rat are extended. By applying the inequality principle (Tindall & Wilson, 1988) it was confirmed with a probability of error of 1 in 10(10) that N. brasiliensis larvae applied to the skin passed through the lungs on their way to the intestine. Taking the analysis further, migrating larvae of S. ratti or N. brasiliensis were extracted from the nose or lungs, respectively, of donor rats and transferred to recipients by stomach tube to assay their ability to colonize the intestine. Results showed that (a) changes undergone by each parasite in its proven, specific transit site were essential before larvae could establish in the intestines of recipients, (b) these changes could be monitored by morphological criteria, and [corrected] (c) these changes were not completed until larvae had been in the nose or lung for a significant period. It follows from (c) that anywhere in the body of the host, termed a 'nursery', that supports a substantial amount of this mandatory development must be detectable by the conventional procedure of sampling at autopsy. Conversely, absence of parasites judged by sampling at autopsy is positive proof that a site is not a nursery when sampling is timed in relation to reliable estimates of overall kinetics (Tindall & Wilson, 1990), and with control information on the efficiency of sampling. Comparative data from sampling at autopsy using the same extraction techniques for both species met these criteria: they demonstrated that no part of the head of the rat was a nursery for N. brasiliensis, and that the lung did not serve in this capacity for S. ratti.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Diaper performance: maintenance of healthy skin.

Skin wetness is proportional to diaper wetness, and with increased skin wetness, the potential for diaper dermatitis is increased. This study evaluated a wide range of infant diaper products. Eighty healthy volunteers wore 2-inch wetted diaper patches on their volar forearm for two hours. An evaporimeter was used to measure excess skin wetness attributed to the patches. The amount of moisture retained in the patch was also calculated. We found that superabsorbent (SA) disposable diapers kept the skin drier and retained more synthetic urine than cloth reusable and conventional disposable brands, and thus have the greatest potential for helping prevent diaper dermatitis. The SA brands evaluated did an equally adequate job in keeping the skin dry and in retaining moisture. Conventional disposable diapers were less able to keep the skin dry than SA diapers and were not superior to cloth products in most instances. Cloth diapers' performance depended on their composition. Those with several layers of the same fabric were less successful in keeping the skin dry than ones that contained middle layers of different nonwoven components.

Diaper Rash

Cell intercalation during notochord development in Xenopus laevis.

Morphometric data from scanning electron micrographs (SEM) of cells in intact embryos and high-resolution time-lapse recordings of cell behavior in cultured explants were used to analyze the cellular events underlying the morphogenesis of the notochord during gastrulation and neurulation of Xenopus laevis. The notochord becomes longer, narrower, and thicker as it changes its shape and arrangement and as more cells are added at the posterior end. The events of notochord development fall into three phases. In the first phase, occurring in the late gastrula, the cells of the notochord become distinct from those of the somitic mesoderm on either side. Boundaries form between the two tissues, as motile activity at the boundary is replaced by stabilizing lamelliform protrusions in the plane of the boundary. In the second phase, spanning the late gastrula and early neurula, cell intercalation causes the notochord to narrow, thicken, and lengthen. Its cells elongate and align mediolaterally as they rearrange. Both protrusive activity and its effectiveness are biased: the anterioposterior (AP) margins of the cells advance and retract but produce much less translocation than the more active left and right ends. The cell surfaces composing the lateral boundaries of the notochord remain inactive. In the last phase, lasting from the mid- to late neurula stage, the increasingly flattened cells spread at all their interior margins, transforming the notochord into a cylindrical structure resembling a stack of pizza slices. The notochord is also lengthened by the addition of cells to its posterior end from the circumblastoporal ring of mesoderm. Our results show that directional cell movements underlie cell intercalation and raise specific questions about the cell polarity, contact behavior, and mechanics underlying these movements. They also demonstrate that the notochord is built by several distinct but carefully coordinated processes, each working within a well-defined geometric and mechanical environment.

Animals

The course of infection in rats given small primary doses of Strongyloides ratti and S. venezuelensis.

Development of exact doses (less than 100) of Strongyloides venezuelensis third-stage larvae in adult Wistar rats was insignificant (mean proportion of 0.076 of the dose at day 8, n = 16) compared with a homogonic strain of S. ratti (0.538, n = 6; 0.726, n = 6) and heterogonic S. ratti (0.681, n = 6). Newly-weaned Wistars allowed development of a mean proportion of S. venezuelensis of 0.298 (n = 4) compared with 0.013 (n = 4) of the same sample of larvae in adult hosts. Experiments with 75Se-labelled larvae established that S. venezuelensis effectively failed to migrate from skin to intestine in adult animals, while mean proportions of 0.141 (n = 5) and 0.138 (n = 4) of the label was found in the intestines of newly-weaned rats 72 h after skin application. Labelled larvae of homogonic S. ratti migrated equally well in both age groups of host (0.350 and 0.358 in 12- and 3-week-olds respectively). Adult S. venezuelensis transferred surgically to the intestines of previously uninfected full-grown Wistars survived over a 21-day period to the same extent as either strain of S. ratti. Resistance of Wistar rats to S. venezuelensis therefore appears to affect the migratory stage preferentially. S. venezuelensis developed better in mature PVG inbred rats (mean = 0.301, n = 20). Studies of S. ratti showed that infections of both strains initiated by exact (less than 100) doses in Wistar rats had decayed to insignificance between days 26 and 32. The rate of loss of adults of the heterogonic strain was significantly greater than that for the homogonic. The egg content of worms declined as infection progressed and rats were idiosyncratic in their influence on parasite reproduction from the earliest time of sampling (8 d). It was established that 'autoinfection' was an unlikely feature of the biology of homogonic S. ratti following the surgical transfer of 450 first-stage larvae to the intestines of 8 adult Wistar rats. No evidence of infection appeared in the guts of these animals 8 days post-transfer. The significance of these results in terms of the biology of Strongyloides spp. naturally occurring in the rat is discussed.

Animals

Psychosocial responses to the threat of HIV exposure among people with bleeding disorders.

The findings of a state-wide needs assessment of people with bleeding disorders at risk of human immunodeficiency virus (HIV) infection are reported. The effects of the threat of HIV exposure on the psychosocial functioning of respondents is assessed. A total of 394 of 796 (49 percent) persons aged 14 years and older responded to a questionnaire. Psychological distress, marital distress, AIDS-related dating problems, and AIDS-related sexual problems were examined. Potential predictors were illness-related indicators, subjective assessments of sources and consequences of vulnerability to HIV, social sources of distress such as AIDS-related isolation and discrimination, and behaviors respondents engaged in to assess or reduce their risk of infection. The implications of these findings for service provision are discussed.

Acquired Immunodeficiency Syndrome

Cell rearrangement and segmentation in Xenopus: direct observation of cultured explants.

We make use of a novel system of explant culture and high resolution video-film recording to analyse for the first time the cell behaviour underlying convergent extension and segmentation in the somitic mesoderm of Xenopus. We find that a sequence of activities sweeps through the somitic mesoderm from anterior to posterior during gastrulation and neurulation, beginning with radial cell intercalation or thinning, continuing with mediolateral intercalation and cell elongation, and culminating in segmentation and somite rotation. Radial intercalation at the posterior tip lengthens the tissue, while mediolateral intercalation farther anterior converges it toward the midline. This extension of the somitic mesoderm helps to elongate the dorsal side of intact neurulae. By separating tissues, we demonstrate that cell rearrangement is independent of the notochord, but radial intercalation - and thus the bulk of extension - requires the presence of an epithelium, either endodermal or ectodermal. Segmentation, on the other hand, can proceed in somitic mesoderm isolated at the end of gastrulation. Finally, we discuss the relationship between cell rearrangement and segmentation.

Animals

Criteria for a proof of migration routes of immature parasites inside hosts exemplified by studies of Strongyloides ratti in the rat.

The first rigorous proof applicable to the migration pathway of an infective juvenile macroparasite inside its host is presented. Third-stage larvae of a homogonic strain of Strongyloides ratti applied in exact doses of less than 20 to the skin of the flank of young rats were recovered 16-40 h later in the naso-frontal part of the head. The peak proportion of the dose (po) recovered between 20 and 25 h in this site had a mean value of 0.316 +/- 0.021 in 48 animals. In 40 other rats infected simultaneously the mean proportion of the dose (pf) that reached the small intestine was at least 0.837 +/- 0.013. Proof resides in verification of the inequality po + pf greater than 1. With appropriate statistical tests the excess of the sum of the means of these two proportions over unity is shown to have a probability of occurring by chance of 1 in 3.5 x 10(6). Thus it is effectively certain that the naso-frontal portion of the head is part of at least one pathway taken by this parasite on its way from the skin to the intestine of its host. By suitable protection of the infection site it was confirmed that migration to the head was achieved by an internal route and not as a result of grooming. Larvae were recovered from the cranium in the same rats over the period 15-40 h, but the peak proportion of the dose occurred at 20 h, and po + pf less than 1 in this location. Whether the cranium is also part of the pathway is therefore still undecided. The significance of this novel analysis in the general context of in-host migration of infective stages is discussed and it is concluded, following its application to data sets from other authors, that the only cases in which proof can be demonstrated are the anterior skull of the rat for S. ratti (present data) and the lung of the same host for Nippostrongylus brasiliensis (Twohy, 1956).

Animals

Implantable defibrillation: eight years clinical experience.

Implantation of the first automatic defibrillator occurred in February 1980. Incorporation of cardioversion capability in 1982 resulted in the AICD automatic implantable cardioverter defibrillator. Between April 1, 1982 and April 15, 1988, 3610 patients in 236 U.S. and 84 international centers received AICD pulse generators. Patient population consisted of 2904 males and 683 females with recurrent ventricular tachycardia and/or fibrillation, mean age 59 yrs. (range 9-96 yrs.). Primary diagnoses reported for the patient group were: coronary artery disease (63.5%), nonischemic cardiomyopathy (12.9%), other (6.4%) and unspecified (17.2%). Mean reported LV ejection fraction was 32.8%. Follow-up averaged 12.2 mo. (range 0-72 mo.). Of 385 deaths, 94 (24%) were sudden. Cumulative percentage survival (+/- S.E.) from sudden cardiac death (SCD) was 98.0 +/- 0.3%, 96.5 +/- 0.5%, 95.2 +/- 0.7%, 93.7 +/- 1.0%, 93.7 +/- 1.0% and 89.7 +/- 4.0% at 12, 24, 36, 48, 60 and 72 months, respectively. Operative mortality (less than or equal to 30 days) was 2.5%. Reported side effects/complications were similar to those of pacemakers. To date, 33% of the patients received spontaneous device countershocks. AICD pulse generator survival from electrical and mechanical failures was 92.8 +/- 0.5%, 88.4 +/- 0.7%, 86.7 +/- 0.8% and 86.4 +/- 0.9% at 12, 18, 24 and 30 mos. Data analysis demonstrates that the AICD has had a significant impact on patient survival from SCD.

Death, Sudden

Immunohistochemical evidence for the distribution of nerve growth factor in the embryonic mouse.

The distribution of nerve growth factor-like immunoreactivity has been examined in the embryonic mouse with special reference to the CNS. The intensity of the immunoreactive stain was found to be greatest on embryonic days 15 and 16. The antigen is widespread and present in high concentrations in both the PNS and CNS. Most intense staining was detected in cranial nerve tracts, hippocampus, developing white matter of the spinal cord and tegmentum. Lower intensities were found within diencephalic regions, spinal cord grey matter, medullary fibre tracts and cerebellum. These results support the increasing evidence suggesting that the trophic molecule nerve growth factor has an important role to play in the development of central as well as peripheral neurons.

Animals

Studies of the effect of contralateral versus ipselateral challenge of rats primed on one side with Strongyloides ratti.

The initial pathway of skin penetrating larvae of Strongyloides ratti inside the host is not systemic and could well involve local components of the lymphatic system. The experiments described were an attempt to detect an effect on immunity depending on whether larvae of a challenge infection were committed to a pathway through heavily primed or lightly primed lymph nodes. Female rats were immunised by subcutaneous injection into the right forearm of 10,000 [corrected] heat killed, or 1000 live, third stage larvae of S. ratti. Animals given living parasites were placed on a diet containing 0.1 or 0.2% thiabendazole 48h or 36h after infection. Challenge infections of less than 100 larvae ('exact' doses) were applied on day 21 to either the right or left flank and, similarly, to controls that had received the anthelmintic but not the priming infection. Heat killed parasites elicited no response at all. Priming with live larvae stimulated a significant immunity (16% and 37% depression in 2 experiments), but there was no difference between rats whose challenge was on the same side as the priming dose and those which had the contralateral treatment. The significance of these results to theories of pathfinding in general, and to practical immunology, is discussed.

Analysis of Variance

Developing a hospital's volunteer program.

Today's competitive environment is placing increasing and often conflicting demands on hospital social service departments. In these difficult circumstances, the use of volunteers may help provide services that would not otherwise be available. This article outlines a systematic approach to developing volunteer programs that avoids common pitfalls and is both effective and cost conscious.

Cost-Benefit Analysis

Identification and quantification of mRNA for nerve growth factor in histological preparations.

Hybridization histochemistry has been used to detect mRNA for nerve growth factor (NGF) in histological preparations of mouse salivary glands and rat iris using a 32P-labelled cDNA probe and autoradiography. Label was visible over the tubular cells of the male mouse submaxillary gland but not the sublingual gland. A much lower label density was found over the tubular cells of the female submaxillary gland, whereas sections of liver and pancreas were negative. Quantitative autoradiography allowed the detection of low levels of mRNA for NGF in the rat iris which was elevated by prior culture of the tissue. The results provide direct histological evidence for the presence of specific NGF-mRNA in the mouse submaxillary gland and rat iris, with increased levels following culture.

Animals

Production and transport of endogenous trophic activity in a peripheral nerve following target removal.

High concentrations of trophic factor for sympathetic neurones were found in the discrete nerve which innervates the expansor secundariorum muscle of the chicken wing. Mouse nerve growth factor (NGF) was additive with nerve extract in allowing survival of sympathetic neurones. Antiserum to NGF, while inhibiting outgrowth in response to NGF, only partially blocked survival promoted by the nerve extract. In these characteristics, the nerve extract resembled the previously characterized activity of its target organ. However, after surgical removal of the muscle there was no decrease in the concentration of trophic factors in the nerve 7 days later. Likewise sectioning, crushing or removing a piece of nerve 1 cm from the muscle had little effect on trophic levels after muscle removal. Retrograde transport of the activity occurred in the nerve even in the absence of the muscle. Distal to ligatures placed on the nerve stump 24 h earlier, 60% of the trophic activity was inhibited by an antiserum to mouse NGF suggesting that a chicken form of the molecule is present and transported. In culture, cells of the nerve sheath produced trophic factors, and the rate of production increased greatly during the first 24 h of incubation. Two conclusions are made: the major source of trophic activity in the nerve is Schwann cells and at least two molecules are present, one of which is a chicken form of NGF.

Animals