Children with intellectual and developmental disabilities (IDD) are likely to receive high-risk prescribing practices, such as polypharmacy, long-term use of psychotropic medications, and overuse of antipsychotics. Behavioural interventions, such as applied behavioural analysis, are evidence-based practices for children with IDD and should be the first-line treatment. Short-term use of psychotropic medications may be helpful in reducing the severity and frequency of challenging behaviours while evidence-based behavioural interventions are pursued. In this essay, we offer practical guidelines for better care.

Triazine-resistant (TR) biotypes of weeds normally susceptible (S) to triazine herbicides first were documented in Ontario in 1974. By 1988, at least nine weed species had TR biotypes, and at least 50% of the corn-producing areas were infested. Corn has been grown the longest in the southwestern Ontario, but TR weeds are only a minor problem there. Predominant agronomic practices in the southwest include crop rotation, atrazine use on 60% of corn land, use of other postemergence herbicides, interrow cultivation, little silage corn, and little manure returned to the land. Corn, particularly grain corn, is new as a large hectareage crop in eastern Ontario. However, more than 75% of corn land in that area is infested with two or more TR weed species. Predominant agronomic practices in the east include continuous corn, nearly all fields are atrazine treated, use of postemergence herbicides is not common, cultivation is rare, 25% of the corn is for silage, and manure from corn silage is returned to all cultivated land. Adequate herbicide programs exist to control TR weeds in corn and other crops. However, the spread from field to field and from farm to farm is often rapid, particularly in eastern Ontario.

Newell & Shanks (N&S) argue against the idea that any significant role for unconscious influences on decision making has been established by research to date. Inasmuch as this conclusion applies to the idea of an “intelligent cognitive unconscious,” we would agree. Our concern is that the article could lead the unwary to conclude that there are no unconscious influences on decision making – and never could be. We give reasons why this may not be the case.

Living, intact protoscoleces of the British horse and sheep strains of Echinococcus granulosus were subjected to surface radioiodination procedures using 125I and Iodogen and 125I-Bolton Hunter reagent. Subsequent combined electron microscopy and autoradiography revealed specific surface membrane labelling with the Iodogen procedure, but significant tegumental labelling with the Bolton-Hunter reagent. The two parasite strains yielded different profiles of electrophoretically separated labelled proteins; the Iodogen method, not surprisingly, resulted in a less complex pattern of labelled polypeptides than the Bolton and Hunter reagent.

Sixty-one serum samples selected on the basis of reactivity in the complement fixation (CF) and latex agglutination (LA) test, were further examined for sensitivity and specificity by indirect haemagglutination (IHA), enzyme linked immunosorbent assay (ELISA) and defined antigen substrate spheres (DASS). Twenty sera from healthy Europeans and 48 samples from patients with either schistosomiasis or trichinosis were also tested. Comparable levels of sensitivity were found between the CF and LA positive sera and IHA, ELISA and DASS. Of the CF positive LA negative group of sera, many were positive by DASS but only a few reacted in IHA and ELISA. Some cross reactivity was also observed in the schistosomiasis sera tested by IHA and ELISA.

The Rosroe Peninsula, on the south side of Killary Harbour, Co. Galway, is formed of the Rosroe Grits, mapped by the Geological Survey of Ireland (1875) as “Lower Silurian”. Kilroe (1907) in a rapid revisionary survey of Galway and Mayo, described the succession on Rosroe as inverted (op. cit. p. 154, n. 3):—

“ Mr. McHenry informs me that the fossils (graptolites) on the south side are indicative of Upper Llandeilo, while those on the north side are Lower. This being the case, the order of the beds is inverted, as they dip northerly.”

Treatment of BALB/c or MF1 mice with cyclosporin A (CsA) around the time of infection with Schistosoma mansoni conferred almost complete protection. The migration kinetics of L-[75Se]selenomethionine-labelled infective cercariae were investigated by compressed tissue autoradiography. Similar levels of skin penetration were achieved by cercariae in control and drug-treated individuals. CsA arrested 87–94% of the worms in the skin and ultimately all of these died in this site. Few worms (7–14%) migrated from the skin to the lungs and none completed migration to the liver. Nevertheless, the autoradiograms revealed a limited degree of lateral cutaneous migration by the worms present in the skins of CsA-treated mice. Results of perfusion recovery experiments carried out during the course of infection reinforced the tracking data.

The freeze fracture technique has been used to quantify changes in the integral components of the double outer membrane of Schistosoma mansoni during the 6-week period of development within the mouse. The intramembraneous particle (IMP) density on the P1 face begins to rise Within 6 h of host penetration, reaches a maximum at day 4 and then falls rapidly after day 9, so that it is at a low level between 3 and 6 weeks. The E1 face IMP density follows the same course as that of the P1 face except that maximum particle density is recorded on day 1 and the counts begin to fall on day 5. The IMP density on the P1 face remains at a consistently low level throughout development. The E2 face IMP density rises gradually to a peak at day 4, when the parasites have migrated to the lungs, and remains thereafter at a similar level, so that by 6 weeks the E2 face has a higher IMP density than the other three fracture faces. The E2 face IMP show a marked increase in size on day 4. Morphological studies indicate that a different type of inclusion body makes a transient appearance in the tegument of the lung worms, and immunocytochemical techniques show the lung worms to be nonimmunogenic. It is suggested, therefore, that the E2 face IMP may represent complexes of parasite antigens and acquired host antigens. The tegumental membranes of cultured specimens have also been examined by freeze fracturing and the IMP densities compared with those obtained from in vivo parasites; the cultured schistosomula have a lower E2 face particle density than the in vivo specimens.

Laboratory rodents vaccinated with highly irradiated cercariae of Schistosoma mansoni develop significant levels of specific acquired resistance yet effect challenge elimination in different organs. Mice and guinea-pigs are at opposite ends of the spectrum in this respect since, in our hands, vaccinated mice kill challenge parasites in the skin whereas vaccinated guinea-pigs kill challenge parasites predominantly in the liver. To determine whether this phenomenon is host-dependent (site) or parasite-dependent (stage), we have transferred worms harvested from mice or guinea-pigs into vaccinated recipient guinea-pigs. The results show that mouse-derived 5-day lung worms and 9-day liver worms that are essentially refractory to vaccine resistance in mice are indeed susceptible to vaccine resistance in guinea-pigs. Identical levels of susceptibility were recorded for lung-stage larvae introduced via the foot vein so as to experience lung and liver mechanisms, or via the mesenteric vein to bypass the lung, thereby confirming that vaccine resistance in guinea-pigs operates in the liver. Mouse worms and guinea-pig worms exhibited equivalent levels of susceptibility at all stages of development. Thirteen-day-old larvae from either donor species were on the border-line of vulnerability, while 20-day-old worms were totally refractory to vaccine immunity in guinea-pigs. These data show that vaccine immunity in different rodent species is a site-dependent, rather than a stage-dependent phenomenon. There is, however, an upper age limit of schistosome vulnerability which is common to worms harvested from different donor species.

Naive CBA/Ca mice and CBA/Ca mice vaccinated 4 weeks previously with radiation-attenuated cercariae of Schistosoma mansoni were subjected to 550 rad of whole body (gamma) irradiation and then challenged 3 days laterwith normal cercariae. The perfusion recovery data showed that this procedure reduced theprimary worm burden in naive mice by 22% and the challenge worm burden in vaccinated mice by 82%. Irradiation also ablated the peripheral blood leucocytes of both mouse groups by 90%–100% at the time of challenge. Histological data revealed that such treatment caused a dramatic change in number, size and leucocyte composition of cutaneous inflammatory skin reactions that characterize challenged vaccinated mice and are known to entrap invading larvae; cutaneous eosinophils were preferentially abolished by this treatment. Polyvaccine mouse serum that conferred protection passively upon naive recipient mice, failed to protect naive/irradiated mice when administered by the same protocol. Distraction of macrophages by treatment of mice with silica did not affect the establishment of a primary worm burden and reduced the protection exhibited by vaccinated mice by only 16%. These data indicate that radio-sensitive cells are important to both innate and specific acquired resistance in this mouse model and that macrophages contribute only marginally to the expression of vaccine immunity.

It has been shown elsewhere that the immunosuppressive drug cyclosporin A (CsA) exerts profound schistosomicidal activity when given to infected mice via a multiple administration regime. We show here that a single treatment regime also effects significant reductions in worm burden. Moreover, drug efficacy is maintained at CsA concentrations shown to be subimmunosuppressive in other systems. Subcutaneous treatment effected higher levels of schistosomicidal activity than intraperitoneal or oral treatment, irrespective of whether the drug was given prior to or during infection. Topical application of CsA to the skin site of cercarial penetration, prior to infection resulted in no reduction in worm burden. Systemic release of CsA from a slowly adsorbed, oil-based drug-vehicle combination effected greater levels of killing than when CsA was dissolved in an aqueous drug vehicle. All developmental stages of Schistosoma mansoni were susceptible to killing by a single dose of CsA but, in the case of liver-stage worms, an increased concentration of drug and a longer period between treatment and portal perfusion were needed for killing to be measurable as a reduction in worm numbers.

This study addresses the humoral and cellular basis of specific acquired immunity in the guinea-pig irradiated vaccine model of schistosomiasis mansoni. Rodents vaccinated with 500 gamma-irradiated cercariae and then splenectomized 4·5 weeks later showed a 33% reduction in resistance to challenge as compared to vaccinated animals or vaccinated/sham splenectomized controls. Serum harvested from once vaccinated individuals conferred modest levels of resistance upon naive recipients in some experiments, but transfer was not achieved consistently. Serum from vaccinated and thrice boosted rodents (Vbbb) routinely transferred around 45% immunity, however, provided it was given in 4 ml aliquots on day 9 post-challenge; Vbbb serum thus transferred 50% of donor immunity. Interestingly, multiple doses of this protective serum given on and either side of day 9 did not enhance the protection achieved with a single 4 ml aliquot. Neither peripheral lymph node cells nor splenocytes from the polyvaccinated serum donors were able to transfer resistance to recipient guinea-pigs and they failed to augment the protection achieved with Vbbb serum. Food-pad testing revealed no correlation between delayed hypersensitivity responses and immunity to challenge in vaccinated guinea-pigs. Although polyvaccine guinea-pig serum successfully protected homologous recipients, it failed to protect mice when administered either at the time of challenge (the optimal schedule for transfer of polyvaccine mouse serum), or around day 9 (the optimal schedule for guinea-pigs). Similarly, guinea-pigs could not be protected with polyvaccine rat serum that conferred 75% resistance upon naive recipient rats.

The pulmonary and portal vasculature of naïve mice of the 129/Ola and CBA/Ca strains has been studied by means of the vasculature casting technique. This involves injection of pigmented vinylite resin into the arterial and venous systems, followed by digestion of the tissues with KOH. The peripheral vessels of the arterial and portal systems of CBA/Ca mice were numerous and highly branched. In contrast, casts prepared from 70–80% of naïve 129/Ola mice showed dramatic reductions in the number and extent of the peripheral vessels. In addition, such vessels appeared severely truncated. The remaining 20–30% of naïve 129/Ola mice yielded lung and liver casts that were indistinguishable from the CBA/Ca casts. Casts prepared from 129/Ola mice infected 6 weeks previously with Schistosoma mansoni cercariae showed the same segregation; faecal smears, together with observations of presence or absence of gross pathology in such mice confirmed that the vascular changes correlated with the ‘non-permissive trait’. We propose that such alterations facilitate the reportedly abnormal migration of schistosomes from the liver to the lungs in ‘non-permissive’ 129/Ola mice.

A number of authors have demonstrated that the schistosomicidal compound, Praziquantel (Pzq), depends for its action upon the immune status of the host (Sabah et al. 1985; Brindley & Sher, 1987; Doenhoff et al. 1987). We have attempted to define the synergistic interaction between immuno- and chemotherapy further, using the murine irradiated vaccine model of schistosomiasis mansoni. In vaccinated mice, resistance operates in the skin but not the lungs; drug targeted towards lung-stage worms exacerbates lung-phase immunity, however, as depicted by the increased number and size of inflammatory reactions in the pulmonary tissues. Parasites are often found trapped within such foci. In the present investigation, light and ultrastructural studies have been utilized to examine the nature and extent of damage inflicted upon lung-stage larvae recovered from day 6 Pzq-treated vaccinated mice. Such studies have revealed that damage involves muscle disorganization, internal disruption and occasionally, loss of the tegument; in the latter case, cells are often seen attached to the denuded lung worms. To identify the crucial cellular effector cell(s) involved in the synergy between immuno- and chemotherapy, cell depletion studies have been performed in vivo. It would appear from these experiments that eosinophils or lymphocytes rather than neutrophils or macrophages are important effector cells in this synergy. Histological studies argue in favour of eosinophils being the key effector cells.

Antigens sharing determinants with surface membranes and soluble proteins of adult Schistosoma mansoni have been detected in culture media after incubation of radioactively labelled worms. The relative quantities of these antigens were measured with specific antisera raised in rabbits and with serum from an immune rhesus monkey. It was found that 12–16% of TCA-precipitable radioactivity in the culture medium consisted of membrane antigens and 6–8% consisted of antigens sharing determinants with proteins found in the soluble fraction of adult worms. Over half the membrane antigens were present in particulate form, while other antigens were present in solution. Surface labelling the adult worms with [125I]confirmed that some of the particles in the culture medium were derived from the surface membrane of the adult worm and electron microscope examination of such particles showed that large membrane fragments were present. These results support the hypothesis that anti-bodies against schistosome membrane antigens are induced by particulate membrane antigens released by the parasite.