Search PubMed⌕ Search

Biomedical subjects

P Hagan

Publications and source records attributed to P Hagan.

89 records · Page 5Linked to original sources

Eosinophilia and resistance to Schistosoma haematobium in man.

We have measured the levels of infection with Schistosoma haematobium in children resident in an endemic area of The Gambia before and 3 months after successful chemotherapy and following reinfection. An exposure index was calculated from data collected on water contact, cercarial densities and infected snail densities at water contact sites. Peripheral blood eosinophil levels were recorded and the ability of serum (heat inactivated) from the children to allow killing of schistosomula of S. haematobium was examined. Of 50 children with a post-treatment egg count of less than 1 ovum/10 ml urine, 26 were classified as reinfected, acquiring greater than 1 ovum/10 ml urine over the transmission season. Twenty-four were classified as not reinfected, acquiring less than 1 ovum/10 ml of urine over the same period. These two groups did not differ with respect to their estimated age, weight or pretreatment egg counts. Children who were reinfected had significantly higher levels of exposure and significantly lower peripheral blood eosinophil counts than children who were not reinfected. At all levels of exposure children with high eosinophil counts were less likely to be reinfected than those with lower counts. But antibody-dependent, complement-independent killing of schistosomula of S. haematobium by eosinophils was barely detectable and did not differ between reinfected and non reinfected groups. These observations suggest that subjects with elevated counts are less susceptible to reinfection but the mechanisms involved are not apparent.

Adolescent↗

Leishmaniasis in The Gambia. 3. Is its incidence increasing?

During 1982 a further case of visceral leishmaniasis and six cases of cutaneous leishmaniasis were seen at the Medical Research Council Laboratories in The Gambia, suggesting that the incidence of this infection in The Gambia is increasing.

Adolescent↗

Structure-activity relationships of various bisphosphonates.

A variety of bisphosphonates with aliphatic side chains of increasing length, as well as 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP, formerly APD), dichloromethylene-bisphosphonate (Cl2MBP, formerly Cl2MDP), and dibromomethylene bisphosphonate (Br2MBP, formerly Br2MDP), were compared in vitro and in vivo to find (a) a possible relationship between structure and activity in order to give some indication about their mechanism(s) of action on bone and (b) the most efficient and safe compound having an effect on bone resorption. Some relationship was found between inhibition of calcium phosphate precipitation in vitro and of mineralization in vivo. No correlation existed, however, between any parameter measured and bone resorption. The number of calvaria cells in culture was decreased by compounds with a chain length greater than 5-C, by AHPrBP, Cl2MBP, and Br2MBP. Lactate production by these cells in vitro was increased by the long chain bisphosphonates and AHPrBP, and was decreased by Cl2MBP. No good correlation existed between the inhibition of bone resorption measured in vitro on calvaria and that seen in vivo on rat tibiae metaphyses. The latter was inhibited the most efficiently by the bisphosphonates longer than 5-C and by AHPrBP; these were 10 times more effective than Cl2MBP. Taking into account all factors, 1-hydroxypentylidene-1,1-bisphosphonate and AHPrBP seem to be the most active compounds to inhibit bone resorption.

Alkaline Phosphatase↗

Stimulation of immunity to Nematospiroides dubius in mice using larvae attenuated by cobalt 60 irradiation.

Infective larvae of Nematospiroides dubius attenuated by cobalt 60 irradiation are extremely effective at stimulating immunity. Previously, such levels of protection could only be obtained with multiple immunizations of normal larvae. The critical factor underlying this protective response appears to be the dose of irradiation given to the immunizing infection. Various doses of irradiation have been tested and the most effective of these range between 10 and 30 krad. The experiments show that provided this level of irradiation is used, the number of immunizing infections is relatively unimportant. Such use of irradiated larvae will be of value in attempting to analyse the immune mechanisms which operate against N. dubius. The possible mechanisms of immunity to N. dubius are discussed.

Animals↗

The effect of gamma irradiation on Nematospiroides dubius. Factors affecting the survival of worms in a primary infection in mice.

The infective larvae of Nematospiroides dubius were exposed to various levels (0-30 krad) of gamma irradiation by means of a Cobalt 60 source. Groups of mice were infected with these larvae and autopsied 5 weeks later for worm counts. It was found that male worms were more susceptible to irradiation than female worms. In both instances, however, the survival curve on a semi logarithmic plot was characterised by a shoulder at low doses and an exponential component at the higher levels of exposure. No male worms were recovered from mice infected with larvae given more than 12 krad but some female worms were capable of surviving 20 krad. The fecundity of female worms was reduced by 61% at 4 krad and totally ablated at 8 krad. Further experiments demonstrated that the survival of irradiated N. dubius in vivo was related to the extent of the damage caused at the time of irradiation and was not dependent on additional host parameters. Thus neither the number of irradiated worms inoculated nor the sex of the host radically altered the sex ratio or proportion of the worms lost as a result of irradiating the larvae. Furthermore, treatment with cortisone or sublethal irradiation of the host did not increase the proportion of surviving worms. It was, therefore, concluded that a host immune response was not involved.

Animals↗

Tissue distribution of 203 Pb-acetate: comparison with 67 Ga-citrate as an abscess-localizing agent.

Since 203Pb-acetate accumulates in necrotic tumor tissue, the possibility was raised that it might also accumulate in other necrotic tissue such as abscess. We first studied the tissue distribution and excretion of 203Pb-acetate in control rats at 4, 24, 48, 72, and 96 hr. An enterohepatic circulation for lead is suggested. We then compared the uptakes of 203Pb-acetate and 67Ga-citrate in experimental abscesses in rats. The mean gallium accumulation in the abscess was 10 times that of lead at 24 hr and 12 times that of lead at 72 hr. The abscess-to-tissue ratios were greater for gallium for every tissue examined, although the abscessed areas were clearly visualized by scanning at 24 and 72 hr with both agents. With the exception of blood, abscess-to-tissue ratios for 67Ga at 24 hr were higher than or equal to those at 72 hr. However, the 67Ga ratios for the inflamed tissue surrounding the abscess to muscle and blood were higher at 72 hr than at 24 hr, which suggests that inflammation without abscess might be better identified by gallium scanning at 72 hr.

Abscess↗

Antibody to schistosomulum surface carbohydrate epitopes in subjects infected with Schistosoma haematobium.

The binding of immunoglobulin to carbohydrate epitopes on the surface of Schistosoma mansoni schistosomula was measured with 125I-labelled protein A in sera from 67 Gambian subjects living in a focus of intense S. haematobium transmission. The levels of such antibody differed considerably between subjects and there was significant variation between age groups. The highest mean level, in subjects aged between 8 and 14 years, was significantly greater than that in older subjects. Previous studies have shown that resistance to post-treatment reinfection with S. haematobium is related to age in this focus, and is greatest in those aged 15 or more years. These differing relationships with age suggest that antibodies directed against carbohydrate epitopes on the surface of the schistosomulum do not have a major protective role in man.

Adolescent↗

Cytokines and perinatal brain injury.

A rapidly expanding body of data provides support for the hypothesis that pro-inflammatory cytokines including interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) are expressed acutely in injured brain and contribute to progressive neuronal damage. Little is known about the pathogenetic role of these cytokines in perinatal brain injury. Recent experimental studies have incorporated two closely related in vivo perinatal rodent brain injury models to evaluate the role(s) of pro-inflammatory cytokines in the progression of neuronal injury: a perinatal stroke model, elicited by unilateral carotid artery ligation and subsequent timed exposure to 8% oxygen in 7-day-old rats, and a model of excitotoxic injury, elicited by stereotactic intra-cerebral injection of the selective excitatory amino acid agonist NMDA. Each of these lesioning methods results in reproducible, quantifiable focal forebrain injury at this developmental stage. Acute brain injury, evoked by cerebral hypoxia-ischemia or excitotoxin lesioning, results in transient marked increases in expression of IL-1 beta, and TNF-alpha mRNA in brain regions susceptible to irreversible injury, and there is evidence that pharmacological antagonism of IL-1 receptors can attenuate injury in both models. Recent studies also suggest that complementary strategies, based on pharmacological antagonism of platelet activating factor and on neutrophil depletion can also limit the extent of irreversible injury. In summary, current data suggest that pro-inflammatory cytokines contribute to the progression of perinatal brain injury, and that these mediators are important targets for neuroprotective interventions in the acute post-injury period.

Animals↗

Detection, quantitation and contrast enhancement of myocardial infarction utilizing computerized axial tomography: comparison with histochemical staining and 99mTc-pyrophosphate imaging.

The potential role of the CAT scan in detecting and quantitating acute myocardial infarctions was assessed in the excised hearts of 25 dogs with 48-hour-old myocardial infarctions. The CAT scan detected the infarct in every instance and distinguished subendocardial from transmural infarctions. While the CAT scan slightly underestimated the volume of infarcted tissue, this volume had a close linear relationship to the true volume determined by histochemical staining. On the other hand, the 99mTc-pyrophosphate scintiscans grossly overestimated the volume of infarcted tissue. Intravenous administration of contrast material prior to sacrifice produced contrast enhancement either of the rim or diffusely throughout the infarct. Thus CAT should have an important role not only in detecting but also in estimating the volume of acute myocardial infarctions.

Animals↗

The effect of certain variables on the tumor and tissue distribution of tracers. III. Salicylates and vasoactive drugs.

Attempts were made to increase the viable tumor concentration of 54Mn and 67Ga in a rat hepatoma model by administering rat angiotensin, tolazoline, and salicylates. Salicylates increased the tumor concentrations of 54Mn and improved 65Mn viable tumor/background ratios. 67Ga was not affected by the salicylates. The salicylate effect appeared to be mediated by intracellular mechanisms rather than alterations in plasma protein binding. Rat angiotensin slightly increased the concentrations of 67Ga in the tumors but not enough to suggest that it would be useful clinically. Tolazoline did not increase tumor uptake of the tracers.

Animals↗