Expression of intercellular adhesion molecule-1 and lymphocytefunction-associated antigen-1 in experimental Schistosoma mansoni infection and in synchronous periparticular hepatic granulomas in mice: immunohistochemistry, confocal laser scanning microscopy, and immunoelectron microscopy

Adhesion molecules play an important role in inflammatory and immunological responses. We assessed the expression pattern of intercellular adhesion molecule-1 (ICAM-1) and lymphocytefunction-associated antigen-1 (LFA-1) in the livers of mice experimentally infected with Schistosoma mansoni and in synchronous hepatic granulomas induced by injection of soluble egg antigen (SEA)-coupled Sepharose beads in a mesenteric vein of mice. By immunohistochemistry, confocal laser scanning microscopy, and immunoelectron microscopy, ICAM-1 was localized on endothelial cells, sinusoidal-lining cells (Kupffer cells and sinusoidal endothelium), the hepatocyte cell membrane facing Disse's space, and inflammatory cells in the granuloma. LFA-1 was visualized on the inflammatory cells of the granuloma and on phagocytic sinusoidal-lining cells, most likely Kupffer cells. ICAM-1- and LFA-1-immunoreactive cells were present in the granuloma as early as at 3 days after injection of SEA-coupled beads and persisted with time. As granulomas became older, nonimmunoreactive granuloma cells appeared. We conclude that adhesion molecules play an important role in the genesis of the schistosomal granuloma. Received: 16 September 1996 / Accepted: 24 October 1996     

Hospitals in sub-Saharan Africa: why we need more of what does not work as it should

This paper analyses the origins of today's crisis in the hospital sector in sub-Saharan Africa. Present trends in availability of hospital services are extrapolated to the future in order to provide a low-end estimate of the need for expansion of first referral level hospitals. This will not be possible without giving due priority to this sector, a commitment to considerable investments and reorientation of resources from tertiary to first referral level hospitals. It is to be feared that if this is not done, the backlog will increase, and, given the time lag before investments translate into operational services, there will be a major shortage of hospital services in sub-Saharan Africa within a decade.     

Ivermectin for the chemotherapy of bancroftian filariasis: a meta-analysis of the effect of single treatment

Summary The efficacy and safety of ivermectin in the treatment of filariasis due to Wuchereria bancrofti was assessed by a meta-analysis of the results from 15 published clinical trials. Seven hundred and forty-eight microfilaraemic patients were enrolled in 7 dose-finding and 8 comparative studies. Administered as a single dose, ivermectin induced nearly complete clearance of microfilariae from the blood from the first day to 30 days post-treatment, followed by gradual recurrence of microfilaraemia and increase in its intensity. Higher doses of ivermectin showed greater clearance effects and maintained lower microfilaraemia levels for a longer time. The adverse reactions caused by the drug were flu-like, transient, generally mild and well tolerated by patients. The frequency and intensity of adverse reactions were strongly associated with pretreatment microfilaria counts in the blood, but independent of dose. The findings of the meta-analysis suggest that ivermectin given at a single annual dose of 200 μg/kg body weight or higher, whether or not in combination with DEC, has great potential for therapeutic strategies to control bancroftian filariasis.     

Evaluation of nocturnal bronchoconstriction by all night tracheal sound monitoring.

BACKGROUND: A study was undertaken to evaluate the reliability of a digital tracheal sound analyser (ELENS-DSA) in predicting nocturnal changes in airways resistance in asthmatic patients. This device allows continuous measurement of the proportion of the time occupied by wheezing (Wh%). METHODS: Nocturnal polygraphic studies with simultaneous continuous monitoring of tracheal sounds and airways resistance were performed in seven patients with nocturnal asthma. In order to evaluate the possible bias in wheezing estimation, each tracheal sound recording was passed through the automatic analyser and simultaneously monitored with earphones by an experienced observer. RESULTS: The device detected audible wheezing with an optimal sensitivity and specificity of 70%. Snoring was a minor cause of the relatively poor characteristics of the system. A close correlation (p < 0.001) between Wh% and airways resistance was observed only in those patients with the highest increase in resistance; when the results of all the subjects were pooled the correlation observed was poor. The predictive value of Wh% in detecting changes in airways resistance during 10 minute intervals was lower than 70%. The positive and negative predictive values of Wh% were raised to 79% and 83%, respectively, for 30 minute intervals. CONCLUSIONS: The ELENS-DSA system is a relatively crude means of detecting wheezing and assessing bronchoconstriction quantitatively. However, it is able to detect accurately nocturnal bronchoconstriction for 30 minute intervals. This finding, along with the fact that the monitoring is non-invasive, suggests that it may be a promising tool, especially for patients during sleep.     

Primary health care in a multi-level perspective: towards a research agenda

The authors propose to view primary health care (PHC) from a multi-level perspective. Studying how PHC is conceived and implemented at different levels of social organization (e.g. in international agencies, national governments, regional centres of health care and local communities) will reveal which interests may be competing in the planning and execution of what broadly and conveniently is called 'PHC'. Mapping out these conflicting views and interests will contribute towards a better understanding of how PHC works or why it does not work and provide suggestions for a more effective and equitable PHC. Five themes are proposed for a multi-level research approach: (1) vertical versus horizontal organization of PHC: (2) the role of medical personnel in PHC; (3) the distribution of pharmaceuticals; (4) the integration of traditional medicine in PHC; and (5) family planning.     

Sorption of various drugs in polyvinyl chloride, glass, and polyethylene-lined infusion containers

The sorption of chloroquine sulfate, diazepam, isosorbide dinitrate, lorazepam, midazolam, nitroglycerin, promethazine hydrochloride, thiopental sodium, and warfarin sodium to three types of containers was studied. Appropriate amounts of the drugs were added to 500 mL of 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags, glass bottles, and Clear-Flex bags composed of a laminate of polyethylene, nylon, and polypropylene. The containers were stored in the dark at room temperature for 24 hours. Samples were taken at various intervals and assayed for drug concentration by high-performance liquid chromatography. There were no appreciable changes in pH after 24 hours, and all the admixtures remained clear and colorless. The potency of chloroquine sulfate, lorazepam, midazolam, promethazine hydrochloride, and thiopental sodium remained unchanged in glass, PVC, and Clear-Flex containers. Diazepam, isosorbide dinitrate, nitroglycerin, and warfarin sodium did not show any sorption to glass bottles and Clear-Flex bags. In PVC bags, however, up to 55% of diazepam, 23% of isosorbide dinitrate, 51% of nitroglycerin, and 24% of warfarin sodium was lost during the 24-hour study period. Diazepam, isosorbide dinitrate, nitroglycerin, and warfarin sodium in 0.9% sodium chloride injection showed a loss of potency when stored in PVC containers for 24 hours at room temperature, but none of the drugs studied lost potency when stored in glass bottles and Clear-Flex bags.     

Are hypodense eosinophils in children activated or immature?

In patients with allergic asthma and rhinitis high numbers of hypodense eosinophils (HE) have been demonstrated. In a previous study we reported that asthmatic and healthy children had more HE than their adult counterparts. We assumed that this might, in part, he due to the presence of immature eosinophils in children. To distinguish between immature and activated eosinophils, determination of eosinophil cationic protein (ECP) might be interesting as it is known that high serum levels of ECP are associated with increased activation of eosinophiis. In this study we determined (he levels of ECP in scrum in asthmatic and healthy children and adults trying to distinguish activated from immature eosinophils. We found that ECP levels were not increased in children (healthy and asthmatic) compared to adults (healthy and asthmatic). This supports the hypothesis that increased numbers of HE in childhood are, at least in part, immature eosinophils. Nevertheless, we could confirm that inflammation was present in children because soluble interleukin-2-receptor (slL-2R), a marker of lymphocyte activation, was higher in asthmatic children as compared to healthy children. IL-6, a marker of macrophage/monocyte activation, was not different in the different patient groups. We conclude that although signs of inflammation are present in childhood asthma, the increased numbers of HE in children are in part due to the presence of immature eosinophils.     

GABAA receptor-mediated stimulation of non-adrenergic non-cholinergic neurones in the dog ileocolonic junction.

1. The inhibitory effects of gamma-aminobutyric acid (GABA), the GABAA receptor agonist homotaurine and the GABAB receptor agonist (+/-)-baclofen were investigated on circular muscle strips of the dog terminal ileum and ileocolonic junction. 2. In the presence of atropine, GABA and homotaurine induced concentration-dependent relaxations, similar to the non-adrenergic non-cholinergic (NANC)-mediated relaxations evoked by electrical stimulation or by acetylcholine. The ileocolonic junction was more sensitive to GABA and homotaurine than the ileum. (+/-)-Baclofen had no effect. Cross desensitization only occurred between GABA and homotaurine. 3. The GABAA receptor antagonist bicuculline shifted the concentration-response curves to GABA and homotaurine to the right. The maximal relaxation to GABA remained unaffected. 4. GABA-induced relaxations were not inhibited by timolol, guanethidine, domperidone, hexamethonium and desensitization to ATP, but were abolished by tetrodotoxin. 5. Bicuculline, and pretreatment with GABA or (+/-)-baclofen had no effect on the NANC-evoked relaxations to electrical stimulation and acetylcholine. 6. In conclusion, GABA stimulates GABAA receptors located on inhibitory NANC neurones in the dog ileocolonic junction. Our results suggest that it is unlikely that GABA is the final inhibitory NANC neurotransmitter.     

Sociodemographic and behavioral characteristics of HIV antibody-positive blood donors.

This paper describes the sociodemographic and behavioral characteristics of 173 blood donors who were confirmed by Western blot tests to have antibodies to human immunodeficiency virus (HIV), the etiologic agent for acquired immunodeficiency syndrome (AIDS). Seropositive donors were predominantly young, unmarried, and male, and major risk factors could be identified for almost all donors. However, more than 20 per cent of the study participants were women, and many participants were not aware that they were at risk of infection. The heterogeneity of the study population, the lack of awareness among many subjects of risk factors and self-exclusion procedures, and the high level of distress among many subjects after notification, emphasize the need for intensive, well-designed education and support programs.