Enhancing and suppressive effects of tumour necrosis factor/cachectin on growth of Trypanosoma musculi

The effect of human recombinant TNF on the growth of T. musculi has been investigated. When added to parasites cultured in vitro, TNF inhibited their growth. In the presence of thioglycollate-elicited peritoneal exudate cells, the opposite effect was seen and TNF enhanced the growth of trypanosomes in vitro. Similarly, administration of TNF in vivo during the course of infection led to a net increase in the parasite population. It is suggested that TNF exerts a direct antitrypanosomal effect while simultaneously promoting the growth of the parasite through an indirect effect mediated via the host's cells, possibly the macrophages.     

Role of mononuclear phagocytes in elimination of Plasmodium chabaudi AS infection

Summary The role of mononuclear phagocytes in acquired immunity resulting in the intraerythrocytic destruction and elimination of malarial parasites was investigated in the murine model of infection with Plasmodium chabaudi AS. Mice were treated 1 day before or 6 days after infection with agents which either result in augmentation or activation of the non–specific, microbicidal effector function of mononuclear phagocytes or in depletion of cells of this lineage. To examine the effect of agents which activate mononuclear phagocytes, A/J mice, which are susceptible to P. chabaudi AS and exhibit fulminant parasitaemia and death within 10 days of intraperitoneal infection with 10⁶ P–RBC, were treated intravenously with muramyl dipeptide (MDP) or liposome–encapsulated MDP–glycerol dipalmitate (MDP–GDP). Treatment administered 1 day before infection was ineffective. Treatment on day 6 post–infection with liposome–encapsulated MDP–GDP (1 ftg) resulted in a significant decrease in parasitaemia on day 8 and survival, while treatment with free MDP (100 ^g) resulted only in a significant decrease in parasitaemia. To examine the effect of depletion of mononuclear phagocytes, C57BL/6 mice, which are resistant to P. chabaudi AS infection and eliminate the parasite by 4 weeks, were treated intravenously with 3 mg silica. Silica administered 1 day before or 6 days post–infection abrogated resistance resulting in a delay in elimination of the parasite and host mortality. Treatment on day 6 was more effective, with death by day 13 post–infection of 70% of the normally resistant C57BL/6 mice which exhibited fulminant parasitaemia levels. These results thus provide in–vivo evidence that mononuclear phagocytes play a critical role in the elimination of infection with the murine malaria species P. chabaudi AS. Furthermore, these results suggest that the time of administration of agents which alter mononuclear phagocyte function may be important in determining their effect on host antimalarial defences.     

Passive transfer of immunity against hepatic amoebiasis in the hamster by cells

The role of passive cell-mediated transfer of immunity in hepatic amoebiasis in hamsters was studied. The transfer of peritoneal cells from hamsters vaccinated against or protected from hepatic amoebiasis and from those with hepatic amoebiasis, as well as of spleen cells from vaccinated or protected, but not from infected hamsters, conferred immunity against hepatic amoebiasis in recipient normal hamsters. Treatment of the spleen cells from protected hamsters with anti T-cell serum abolished their ability to transfer immunity. It appears that the effector mechanism in this system is T-cell dependent.     

Medical students' attitude towards psychiatry: a ten-year comparison†

Medical students' interest in and attitudes toward psychiatry, both as a field of education and as a medical specialty, have been explored by a number of investigators. The present study compares two series of investigations completed at the McGill University teaching hospitals over a ten year span and involving third year medical students in 1968–69 (n=59) and in 1978–79 (n=168). The findings of these two studies are evaluated in two parts: (1) comparison of attitudes toward psychiatry before and after clinical training in 1978–79. (2) comparison of the results obtained in 1969 with those in 1979. The results of the comparison showed that students currently put more emphasis on the clinical aspects of psychiatric training and less on the theoretical and research aspects of psychiatry. Thirty-two percent of students in 1979 found psychotherapy to be the most useful treatment modality as compared with only 10 percent in 1969. Findings reflecting the usefulness of organic therapies in psychiatry remained fairly consistent, but behaviour therapy was found to be less useful by students in 1979 than in 1969. In the 1969 survey, 2 per cent of the third year students indicated an interest in psychiatry as a future career as compared with 3.3 per cent in 1979. The implications of these findings are discussed in relation to the psychiatric training programmes in medical schools.     

The effect of splenectomy on resistance of mice to Entamoeba histolytica infection

The role of the spleen in amoebic infection was examined in mice, using strains selected as being either genetically-susceptible (C57BL/6) or genetically-resistant (A/J) to amoebiasis. Splenectomized and sham-operated animals were inoculated intracaecally with 2.5 X 10(5) polyxenic trophozoites of E. histolytica at 6, 12 and 15 days post-splenectomy. The animals were killed 6 or 12 days after infection and the parasite burden was evaluated. Removal of the spleen in both susceptible and resistant mouse strains rendered these hosts extremely resistant to amoebic infection by this criterion. Gross examination of the caeca of non-splenectomized, genetically-susceptible mice showed numerous ulcers over the mucosal surface when compared to the splenectomized group which had superficial lesions or none. These observations suggest that the spleen plays a suppressive role in early anti-amoebic resistance.     

Effect of immunosuppression on the size and metastasis of amoebic liver abscesses in hamsters

The effect of T-cell depletion on experimental hepatic amoebiasis in hamsters was investigated. Thymectomized and anti-T-cell (ATS) treated animals as well as sham-operated and unoperated controls were inoculated intrahepatically, following laparotomy, at 7 weeks of age with 1 × 10⁵ axenic trophozoites of Entamoeba histolytica. In neonatally thymectomized hamsters the mean weight of the liver abscess 10 days post-inoculation was significantly greater than in neonatally sham-operated or unoperated controls, but there was no significant difference between these groups of animals in the size of metastatic foci to other organs. On the other hand, a combination of neonatal thymectomy and ATS treatment enhanced both the size of the primary abscess in the liver and the size of metastases to other sites. Adult thymectomy did not have a significant effect either on the size of the primary abscess or on metastatic dissemination of amoebae from the liver. Treatment of hamsters with ATS shortly before or after intrahepatic challenge increased significantly the size of the abscess, but similar treatment 2–3 weeks prior to challenge had no effect. These observations suggest that thymus-dependent cell-mediated immunity plays an important role in the host response to E. histolytica infection.     

Macrophage requirement for host defence against experimental hepatic amoebiasis in the hamster

The role of macrophages in hepatic amoebiasis in hamsters has been investigated by means of their treatment with bacille Calmette-Guérin (BCG) for activation, and with silica for elimination of these cells. Silica-treated animals inoculated intrahepatically with 1 x 10(5) trophozoites of Entamoeba histolytica developed amoebic abscesses in the liver and more metastases to other organs than control animals, and this effect was silica-dose-dependent. In contrast, BCG-treated animals developed significantly smaller abscesses in the liver and fewer metastatic foci. These data suggest that macrophages are involved in host defence against the establishment of amoebic liver abscess and metastatic dissemination of amoebae.     

Is spirituality relevant to the practice of medicine?

The interrelationship between spirituality and medical science has been looked upon with suspicion for centuries. While in ancient societies medicine and religion were intertwined, in the West separation between these two since the Middle Ages has created a wall of mistrust which undermined the relationship. During the last two decades, however, there has been an upsurge of interest in the role of spirituality in medical practice in North American universities. There are a number of reasons for this development. They include an increasing number of patients particularly those with life threatening or chronic diseases who expect their spiritual concerns to be acknowledged and addressed. Furthermore, the unprecedented increase in medical technology has diminished the need for medical practitioners to provide compassionate care and has raised the awareness of physicians of the danger of dehumanization of medical institutions. Consequently, medical education programmes in a growing number of medical schools have begun to implement courses encouraging the integration of spirituality and medicine.     

Genetic control of susceptibility of mice to infection with E. histolytica

Genetic susceptibility to Entamoeba histolytica infection in nine inbred strains and one outbred strain of mice was studied. The number of E. histolytica trophozoites in the ceca of the mice was examined 5 days after intracecal inoculation of axenic amoebae. C3H/HeCr, BALB/c, NZB/BIN, B10.A, DBA/2 and C57BL/6 were susceptible whereas A/J, CE, DBA/1 and CD-1 mouse strains were relatively resistant. Examination of F1 hybrid animals derived from susceptible B10.A and resistant A/J strains of mice showed that susceptibility was dominant over resistance. Segregation analysis of backcross and F2 progeny derived from the same progenitor strains is compatible with the hypothesis that susceptibility to E. histolytica infection in mice is controlled by a single, dominant gene which has been designated Enh. No association was found between the H-2 haplotype and the trait of susceptibility to amoebiasis, indicating that the major histocompatibility complex does not play a major role in regulating the early phase of the response to infection with E. histolytica.     

In vivo activation of macrophages by IFN-γ to kill Entamoeba histolytica trophozoites in vitro

To determine the role of interferon-gamma (IFN-gamma) in the activation of macrophages to kill Entamoeba histolytica trophozoites in vitro, C57BL/6 mice were injected with various doses of recombinant IFN-gamma (rIFN-gamma) by either the intravenous, intraperitoneal or intramuscular routes. Mice were treated with doses of rIFN-gamma ranging from 10(1) to 10(5) units. Twenty hours later, peritoneal macrophages were harvested from the treated animals. Macrophage monolayers were prepared and their in vitro cytotoxic activity against a virulent strain of E. hystolytica (IP:0682:1) was determined. Amoebicidal activity was determined by counting the number of dead trophozoites by Trypan Blue exclusion in cultures containing macrophages and amoebic trophozoites which were incubated together for 4 h. Both intravenous and intraperitoneal treatment resulted in the recovery of macrophages from the peritoneal cavity which exhibited amoebicidal activity in vitro. Peritoneal macrophages harvested from mice that had been treated intraperitoneally or intravenously with rIFN-gamma, however, showed significantly more amoebicidal activity in comparison to macrophages harvested from animals treated intramuscularly. There was a dose dependent relationship between the concentration of rIFN-gamma used to activate macrophages in vivo and the number of dead trophozoites in vitro. In addition, these results confirm our previous observations that treatment in vitro with rIFN-gamma can activate murine peritoneal macrophages to kill amoebic trophozoites.