Opiates and immune function. Consequences on infectious diseases with special reference to AIDS.

There is an increasingly body of evidence, obtained both in vitro and in vivo, showing that exogenous opioids have a variety of effects on cells of the immune system. The consequence is that opiates at pharmacological concentrations suppress cell-mediated immunity, as reflected by depressed T-dependent antibody production by B lymphocytes, altered T lymphocyte functions such as proliferation, delayed-type hypersensitivity, graft-versus-host responses and decreased cytotoxic NK cell activity. The macrophage/monocyte oxidative burst and phagocytosis are also impaired, effects probably mediated by various opioid receptor types as they are blocked or reversed by naloxone, an opioid antagonist. Other possible mechanisms of interaction remain to be elucidated: exogenous opioids can act on neurons of the central nervous system, thereby activating the neuroendocrine system with a subsequent increase in serum glucocorticoid levels. Another potential link between the central nervous system and lymphoid tissue is the sympathetic nervous system, via which opioid-induced activation could result in noradrenergic inhibition of the immune system. The clinical consequences of these suppressive effects on the immune system are seen in the striking increase in the incidence of infections in intravenous opioid addicts. The advent of AIDS and the identification of intravenous drug abusers as a critical risk group have propelled interest in this area. Data obtained both in vitro and in vivo with various experimental models shows that morphine increases susceptibility to bacterial and viral infections, the latter effect possibly being related to a depressive effect of opioids on gamma-interferon levels. The dosage and time of administration strongly influence the results: it appears that chronic opioid treatment in vivo induces a state of immune tolerance, with normal resistance to viral infections, whereas short or single administration has a detrimental effect. In the former context, other factors such as a morphine-induced increase in CD4+ cell numbers may tend to enhance the infectivity of HIV-infected subjects.


[Pharmacology of imidazoline receptors and cardiovascular regulation. Imidazoline receptors and blood pressure].

To explain the central hypotensive action of clonidine- and rilmenidine-type drugs, a recent hypothesis suggested the involvement of imidazoline preferring receptors (IPR) insensitive to catecholamines. Binding studies performed on neuronal membranes prepared from the human Nucleus Reticularis Lateralis area (NRL) showed that rilmenidine was twice as selective as clonidine for the medullary IPRs. Voltammetric experiments revealed that these substances preferentially inhibited the activity of catecholaminergic neurones within the NRL, privileged site for their hypotensive action, rather than the activity of the neurones of the Locus Coeruleus (LC) where these drugs induce their sedative effect. The mechanism of the inhibitory action of these compounds upon the neurones of the NRL definitely involved IPRs when the inhibition of the LC neurones involved classical alpha-2-adrenoceptors. These functional studies also showed that rilmenidine exhibited a selectivity twice as important as clonidine, the reference substance. Poly- and monoclonal anticlonidine antibodies cross-reacting only with imidazolines allowed to detect and immunoreactive substance in the human serum. The amounts of that substance thus measured were higher in some hypertensive patients than in normotensive subjects. The identity of that immunoreactive substance with "endazoline", the endogenous ligand of the IPRs, is presently analysed.


[Study of induced effects by selective CCKB agonists cholecystokinin in the nociception and behavior in rodents].

Potent and selective CCK-B agonists with good bioavailability have been designed by modifying the natural CCK-8 peptide. Thus, BC 264 [Boc-Tyr(SO3H)-gNle-mGly-Trp-Me(Nle)-Asp-PheNH2] is a highly potent (0.15 nM) and selective agonist for CCK-B receptors which cross the blood brain barrier. Following i.v. injection of [3H]pBC 264 in mouse, the ligand was found in its intact form in brain tissue. Analgesic studies and in vivo binding experiments have shown that the CCKergic system could modify the release of endogenous enkephalins, whereas mu and delta opioid receptor activation modulates the release of endogenous CCK. Behavioural studies performed after local injection of CCK-8 or BC 264 into the postero-median part of the nucleus accumbens have shown the involvement of CCK-A receptors in motivation and/or emotional states of rats. In the anterior part, CCK-B receptor stimulation could be involved in attention and memory processes. BC 264 systemically administered in mice increased fear and/or "anxiety" in the black and white box test. In the elevated plus maze, BC 264 increased the emotional responses of the "anxious" rat and decreased these responses in "non anxious" animals. These results suggest that endogenous CCK could play a critical role in mood modulation through CCK-A/CCK-B receptor stimulation. Dysfunctioning of the CCK-A/CCK-B pathways could be implicated in anxiety and panic attacks.


[Cholecystokinins and their receptors. Functional aspects].

The term cholecystokinin (CCK) refers to a family of related peptides whose members play hormonal roles in the gastro-intestinal tract. The sulfated octapeptide CCK-8 [Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2] is also abundant throughout the central nervous system where it satisfies the criteria for a neurotransmitter. CCK interacts with at least two types of receptor called CCK-A and CCK-B receptors. These binding sites can be distinguished on the basis of their affinities for different molecular forms of CCK. Moreover, selective nonpeptide antagonists have been developed for CCK-A and CCK-B receptors. CCK-A receptors occur predominantly at the peripheral level where they are responsible for the digestive effects of CCK: intestinal and biliary smooth muscle contraction, pancreatic enzyme secretion, trophic effects on gastric and intestinal mucosa and regulation of feeding. Some brain CCK-receptors belong to the A-type, but the majority of them are CCK-B receptors. High densities of brain CCK-B receptors are present in cortical and limbic areas such as the amygdala and the hippocampus. At the peripheral level, CCK-B receptor antagonists are active on gastrin receptors, and these two receptors are similar if not identical. Experimental evidence suggests involvement of brain CCK processes in 4 domains: modulation of dopaminergic function, control of pain sensation, anxiety and memory formation. Thus, CCK-B antagonists may be useful to treat certain neuropathological conditions associated with CCK dysfunction.


[Control program of interlaboratory quality for the assay of cyclosporine in biological fluids].

The following article deals with the quality control program proposed since 1988 to the French laboratories performing the measurement of cyclosporine concentration in whole blood or in plasma. First, we describe how the program was organized and its evolution over time. Second, we discuss the main results generated. Those results enable us to state positively that the methods in use at present in the laboratories are precise and give highly reproducible results.


[Buprenorphine abuse in a series of 50 drug addicts hospitalized at a Drug Dependence Evaluation hospital in Marseille].

Buprenorphine, a synthetic central analgesic, marketed since 1987, was rapidly suspected to be subject to abuse. We tried to confirm this abuse in the context of our analytical activity at the Drug Dependence Evaluation and Information Centre. The study was based on 50 drug addicts admitted to Marseille Hospital between June and October 1992. Buprenorphine and its N-dealkylated metabolite were identified in the urine by high performance liquid chromatography equipped with a diode array detector. Nine (18%) of the 50 samples analysed were positive for buprenorphine and/or norbuprenorphine, with a confidence interval of 8 to 28%, which confirms the existence of abuse of this analgesic.


[A rapid method for the determination of the anti-interferon activity of bacteria].

Methods for the rapid and immediate determination of the anti-interferon activity of bacteria have been developed. The use of these methods makes it possible to reduce the time of determination from 48 hours to 24 and 7 hours. The proposed methods require no additional production costs, while their sensitivity and specificity are not inferior to those ensured by the classical method. These methods are recommended for the etiological diagnosis of diseases caused by opportunistic enterobacteria.


[The effect of Lactobacillus acidophilus "Solco" on the immunological indices of totally decontaminated mice under complete gnotobiological isolation].

The possibility of stimulating the immunity of totally decontaminated mice, kept isolated under germ-free conditions, with the use of killed L. acidophilus Solco strains has been studied. As revealed in this study, the oral and intraperitoneal administration of strains O1 and O6 to mice leads to a significant increase in the content of immunoglobulin-synthesizing cells in the jejunal lamina propria of the animals. The oral administration of L. acidophilus Solco strain O6 and the intraperitoneal injection of L. acidophilus Solco strain O1 have been found to lead to a significant rise in the level of luminol-dependent chemiluminescence of mouse peritoneal macrophages. The total decontamination of mice induces the development of secondary immunodeficiency which influences the effectiveness of immunostimulating agents.


[The production of toxic shock syndrome toxins and enterotoxins by Staphylococcus aureus].

The production of toxins of the toxic shock syndrome and enterotoxins by S. aureus of clinical origin was studied by means of commercial standard antisera and standard toxins. The study revealed that among 511 strains isolated in Russia toxigenic ones constituted 41%, and among 592 strains isolated in Czechia toxigenic ones constituted 63%. The capacity for producing toxins may be used as an epidemiological marker.


[The dynamics of detecting group-A streptococci in an infectious disease clinic].

The study revealed that the isolation rate of group A streptococci in scarlet fever patients at the time of hospitalization did not exceed 68%. The isolation rate of these streptococci was greatly influenced by antibacterial therapy carried out before hospitalization. Under clinical conditions with intensive penicillin therapy group A streptococci were eliminated from the larynx on days 3-4. In 13% of children repeated streptococcal infection was observed 0.5-3 months after discharge from hospital.


[The first case of HIV infection in a citizen of the USSR].

The first AIDS patient was a homosexual male who contacted HIV infection in 1982 in Tanzania. In December 1985 the first sign of Kaposi's sarcoma was noted in this patient. HIV infection was diagnosed in him only in February 1987. He was treated with AZT, reaferon, immunoglobulin and underwent electronic therapy. His state of health was stable till February 1991. Then he got severe bacterial pneumonia, candidosis. Pancytopenia progressed. The dose of AZT (0.8 g daily) was increased and intensive antibiotic therapy and the course of diflucan were prescribed. In spite of this treatment the number of CD4 lymphocytes catastrophically decreased (CD4 = 0.01 x 10(9)/l) and the patient died. Thus, more than 63 months passed from the date of the appearance of the first symptoms of AIDS in the patient to his death.


[The prevalence and etiological structure of viral hepatitis in a climatic-geographic area at high risk for infection].

The spread of viral hepatitides on the territory of Central Asia has been analyzed, taking into account regional and territorial factors and using the Fergana Valley as an example. The analysis, based on the use of modern immunochemical, clinico-epidemiological and biochemical criteria, has made it possible to determine the etiological structure of viral hepatitides on the territory of the Fergana Valley. The epidemic outbreak on this territory has been proved to be caused by viral hepatitis E. The necessity of organizing constant epidemiological monitoring on the interstate and territorial level has been substantiated.


[The use of programmed microcomputers for retrospective epidemiological analysis].

In this article two programs for programmed microcalculators, models Elektronika MK-61 and Elektronika MK-52, manufactured in the USSR, are presented. These programs permit the determination of indices describing the dynamics of the epidemic process, both annual and for several years.


[The evolution of meningococcal infection in Mongolia].

On the basis of the generalization and analysis of the results of bacteriological and immunological investigations the epidemic process of meningococcal infection (MI) in Mongolia was found to undergo definite changes during the last 20 years. Group A meningococci prevailing in the etiology of MI were replaced by strains belonging to group B affecting mainly young children (aged up to 3 years). MI morbidity rate caused by group B meningococci was found to be higher in Mongolia than in other countries of the world. These data substantiate the necessity of using more effective remedies for the control of this infection and, in particular, specific immunization with vaccines against group B meningococci; profound study of the properties of the circulating meningococcal strains is to be carried out.


[The laboratory epidemiological study of the joint circulation of the influenza virus A subtypes A/H1N1/ and A/H3N2/ in Bulgaria].

The National Influenza Center of Bulgaria made the epidemiological analysis of the spread of influenza virus, type A, for the period of 11 years on the basis of mass laboratory investigations. Subtype A (H1N1) was found to be the main factor of epidemics in 1978 and 1982, while the epidemics of 1980, 1983, 1985, 1986, 1987 and 1988 were mainly caused by subtype A (H3N2). The data of laboratory and epidemiological studies indicated that after 20-year absence influenza virus A, subtype A (H1N1), was found again to circulate among the population of Bulgaria, and in 1978-1988 circulated simultaneously with the previous subtype A (H3N2). The simultaneous circulation of two subtypes of influenza virus was of great importance for the frequency, spread and duration of influenza epidemics.


[The leading routes and factors in the transmission of the causative agent of campylobacteriosis under current conditions].

Epidemiological investigations carried out at the foci of Campylobacter infection in Moscow and the Moscow region in 1987-1990 demonstrated that Campylobacter infection was recently registered as sporadic cases in a few foci. The alimentary route of the transmission of this infection was the main factor of its spread. A high role of everyday contacts in the spread of this infection was noted. The possibility for outbreaks and sporadic cases of Campylobacter infection to be masked by very frequently occurring associations of these bacteria is discussed.


[The relationship of the antigenic characteristics of the tick-borne encephalitis virus to the level of the protective activity of inactivated cultured vaccines].

As shown in this study, the immunization of animals with killed vaccines against tick-borne encephalitis (TBE) leads to the formation of specific immunity, depending on the antigenic structure of the vaccine strain and the test strains used for challenge. Vaccines obtained on the basis of the TBE virus strain of the Eastern antigenic variant induced the development of a wider spectrum of specific protective activity than vaccines obtained on the basis of the TBE virus strain of the Western antigenic variant.


[Specific circulating immune complexes and antibody titers in candidiasis].

Titers of antibodies to Candida albicans and specific circulating immune complexes have been studied in patients with chronic candidiasis of the genitals, skin and mucous membranes. In most patients with candidiasis of the skin and mucous membranes specific immune complexes have been detected in the blood serum; their determination increases the diagnostic value of serological tests in this disease.


[The use of solid-phase liposomal immunoassay for determining a bacterial antigen of lipopolysaccharide nature].

The solid-phase liposomal immunoassay procedure for the determination of Francisella tularensis lipopolysaccharide (LPS) has been developed. This assay has been made with the use of monolayer liposomes, on the average, 360 nm in diameter with their phospholipid bilayer modified with F. tularensis LPS and their internal space filled with calcein used as fluorescent marker. The assay is based on the principle of the competitive immunosorption of liposomes and antigenic LPS on the surface of polystyrene plates sensitized with specific monoclonal antibodies. The dynamic range of the method is 50-2,500 mg/ml, the variation index being 2.3-11.5%. Optimization of this method and its comparison with the enzyme immunoassay system for the given antigen-antibody pair has been made.


[The immunochemical and biological properties of Leptospira membranes].

The immunochemical and biological properties of purified membrane fractions obtained from Leptospira interrogans, serovar copenhageni, strain Rat 2, and Leptospira biflexa, strain Patoc 1, were studied. The presence of genus-specific and group-specific antigens in leptospiral membranes was established by the methods of immunodiffusion analysis, the microagglutination (MA) and lysis tests. In animal experiments cell membrane preparations produced no toxic and allergic effects. Leptospiral membranes obtained from strain Rat 2 ensured the protection of golden hamsters infected with Leptospira virulent culture and induced antibody production in high titers, detected with the use of the MA test, the lysis test and the enzyme immunoassay, in rabbits immunized in two injections.


[A comparative cytofluorimetric analysis of the blood leukocytes in guinea pigs exposed to the phospholipase D and antigens of the causative agent of plague].

The influence of Y. pestis phospholipase D on the physiological state of leukocytes in the blood of guinea pigs was studied in vivo by flow impulse fluorometry with the use of fluorochrome acridine orange. During the first hours of observation the intensity of leukocyte fluorescence increased due to a rise in the number of polymorphonuclear leukocytes and changes in the permeability of cell membranes. Further changes in the intensity of the fluorescence of the material under study after 24 hours of observation occurred due to the appearance of activated lymphocytes in the blood stream. The processes normalized by day 21. The reaction of blood leukocytes to phospholipase D was specific in comparison with the reaction to capsular antigen, "mouse" toxin, lipopolysaccharide and the main somatic antigen.


[The evaluation of the vibriocidal antibody test in establishing a diagnosis of cholera or Vibrio carriage].

On the basis of the serological survey of cholera patients, vibrio carriers and persons having had contacts with the source or reservoir of Vibrio cholerae the conclusion has been made that the test for the presence of vibriocidal antibodies, together with the bacteriological study of the patient, is of diagnostic importance in the diagnosis of cholera or vibrio carriership. The detection of vibriocidal antibodies, especially in the study of paired sera, permits the detection of cholera cases which have not been bacteriologically confirmed due to various reasons; besides, it makes it possible to exclude the diagnosis of cholera made only on the basis of clinical data. Like bacteriological study, the determination of vibriocidal antibodies must be obligatory for persons hospitalized in a provisory hospital or an isolation ward; it will undoubtedly improve the quality of cholera diagnosis and permit taking timely antiepidemic measures in the focus of infection.


[The clinical assessment of macrophage functional activity in patients with protracted dysentery and its correction with lysozyme and vitamin E].

Prospects for the correction of disturbances in the macrophagal system with a combination of lysozyme and vitamin E in patients with a protracted course of dysentery caused by Shigella flexneri 1b were studied. The phagocytic activity of macrophages (PAM) was found to be suppressed as early as at the beginning of the disease. Out of 38 persons repeatedly found to release shigellae 24 were administered polychemotherapy. PAM indices in patients treated with lysozyme and tocopherol acetate were likely to normalize, this being indicative of the positive effect of these preparations on the functional activity of the macrophagal system.


[The sensitivity of bacterial strains of Yersinia pestis isolated from voles to normal human serum].

The work deals with the results of the study of the viability of Y. pestis strains, isolated from voles in different natural foci of plague, in human normal serum (HNS) and its dependence on the assimilation of ions of exogenic iron. The cultures isolated at the Transcaucasian mountain focus of infection and having no small plasmid pYP were found highly sensitive to HNS. The introduction of the sources of iron, such as hemoglobin or ferritin, into the serum decreased its bactericidal effect.


[The program for early diagnosis of the upper respiratory tract and digestive system neoplasms offered to alcoholics in the region of Friuli-Venice Giulia].

The present study deals with data from an on-going collaborative programme of early diagnosis for upper aero-digestive tract tumors established since 1990 by three ENT Departments of the Friuli-Venezia Giulia Region, Northeastern Italy. The aim of the study was firstly to evaluate the socio-economic characteristics and clinical features of alcoholics in treatment who were offered a free ENT check-up, and secondly to test the feasibility of this type of referral of high-risk patients from non-medical associations to the ENT specialist. A total of 683 patients, of which 151 (78%) were males and 151 (22%) were females, underwent ENT examination. About 25% of the patients were symptomatic, the most frequent symptom being dysphonia (50%) followed by cough (19%), while dyspnoea, dysphagia and pain were present in about 5% of the patients. Other than nearly 50% negative findings, ENT examination revealed a high percentage of inflammatory lesions (30%) of the upper aero-digestive tract. In 37 patients (6%) a precancerous lesion was found and in four cases an histologically confirmed tumor was diagnosed. Although the present study cannot be considered a complete screening, it did clearly evaluate the amount of response given by this high-risk population of alcoholics in treatment to the offer of an ENT examination and gives encouraging results concerning the feasibility of early diagnosis programmes for upper aero-digestive tract tumors which do not follow the normal routine of a sanitary referral by a general practitioner.


[Prospective, cohort, epidemiologic studies of laryngeal neoplasms in Italy].

Recent epidemiological studies show, quite surprisingly, a regression in mortality rates for lung cancer in some of the most industrialized countries of the world. Aetiopathogenetic analogies are made by the Authors in order to verify future trends concerning the incidence of laryngeal cancer in Italy. In this study a particular study model, which furnishes incidence rate expectations for the disease, is elaborated. Comparison of relative risks according to birth dates demonstrates that people born around 1930 are in the higher risk range while younger generations seem to show an effective incidence reduction. Evaluations include that of estimating the period in which the world-wide incidence of the disease will be maximum. With the addition of 70 years (main incidence in the seventh decade) to the year 1930 (the worst year) the study predicts that the end of this century will see the most consistent accumulation of new cases. After the year 2010 a trend towards a gradual regression in incidence will appear. The reasons are probably related to the social and cultural transformations of the last twenty years, particularly the progressive abandoning of the smoking habit.


[Ultrasound staging research of progressive pathology of the base of the tongue].

Diagnosis of tongue tumours is often retarded mainly because tumours grow prevalently in deep muscular layers. A correct exploration of the region might be difficult solely employing clinical examination. Therefore, it would be useful to confirm the suspect of a neoplastic lesion at the base of the tongue with a promptly available imaging method. These considerations led us to evaluate ultrasonography (US) as a diagnostic tool for neoplastic lesions of this region. Initially 10 normal patients were studied in order to become familiar with US anatomy of the area. In a second phase our study involved 24 patients with diagnosed carcinoma of the tongue base and 26 patients with clinical suspect of neoplasm in the region. US examination was carried out with real-time equipment provided by a 5 Mhz convex transducer. Patients were examined in supine position with the neck hyperextended. Longitudinal, oblique and transverse scan of the submental region were obtained. The study showed that US gives detailed images of the floor of the mouth and the tongue. Neoplastic infiltration of the base of the tongue is clearly recognizable as a hypoechoic area. It was possible to detect masses ranging from 1.4 to 3.8 cm. In cases of larger lesions, US was useful in evaluating deep infiltration, whereas in other cases the method allowed the diagnosis of small lesions with submucosal growth. US did not proved to be highly reliable in the diagnosis of lesions confined to superficial planes (false negative results).(ABSTRACT TRUNCATED AT 250 WORDS)


[Positional rhinomanometry in hypertrophic vasomotor chronic rhinitis: considerations before and after functional surgery of turbinates].

The Authors report their experience regarding Positional Active Rhinomanometry performed before and after surgery in hypertrophic-vasomotor chronic rhinitis. Twenty-five patients suffering of hypertrophy of the turbinates and/or nasal vasomotor disorders were examined pre-operatively and 3, 6 and 12 months after inferior submucosal turbinoplasty. Tests were performed in the seated, supina, homolateral and contralateral positions with regard to the fossa in question. Values were compared with those of forty normal subjects. Pre-operative examinations showed a large number of paradoxical responses and very high increase in nasal resistance. Postoperative values were quite similar to those of normal subjects, a demonstration of the efficacy of surgical treatment of turbinates hyper-reactivity.


[Elaboration of the hearing disability scale].

On the basis of a previous pilot study, a multiple-choice questionnaire regarding hearing disabilities was developed. The questionnaire (SDU) was made up of 20 items. The answers were tailored to the single question and scaled according to the increasing degree of disability (form A) or in random order (form B). Administration modality (self-report or interview) and form (A or B) were randomized in a group of 123 adult subjects with different degrees of hearing impairment. Only one factor, attributable to hearing disability, was extracted by factor analysis. This factor explains a major variance ratio of items related to speech perception in difficult listening context. A good correlation (r = .74) was found between SDU total score and hearing threshold in the better ear. No difference in mean score, variance and necessary scoring time of the SDU was found between form A and B. The Authors thus propose the use of form A because of a more easy computation of the total score. Self-report was more time consuming with respect to interview (11.7' vs. 8.4'). Furthermore, self-report was non possible in 13.8% of subjects for severe sign impairment and illiteracy and in 6.1% some form of support was necessary. No difference in mean score and variance between self-report and interview was found. SDU represent a tool for hearing disability evaluation useful in aural rehabilitation protocols. The principal advantage is high applicability thanks to the short time required, simplicity of task and flexibility of administration modality.


[Cisplatin ototoxicity: the experience of the Institute of Oncology in Bari].

The Authors report their experience, developed in the E.N.T. Unit of the Oncologic Institute of Bari, concerning the ototoxic effect of Diamminedichloroplatinum (CDDP). The Study was carried out on 74 patients with advanced cancer of the head and neck, treated according to the polychemotherapeutic scheme called "MBD" in 34 cases and in 40 cases according to the scheme called "Al Sarraf". The otologic evaluation was composed, in all the cases, of a complete series of audio-vestibular investigation, carried out prior to and immediately after every administration chemotherapy and periodically, during a 4 months period after interruption of therapy. Three patients (4%) showed significative acoustical damage, none showed vestibular deficit. Symptoms did not appear beyond the second administration of CDDP, which always followed subjective acouphenic symptomatology. The ototoxic effect of CDDP, resulting in the experience of the Oncologic Institute of Bari, is percentually very low: and seems to be influenced by the single dose, rather than by the total doses and in any case is not preventable by any profilatic measure.


[Modification of vestibular function after radiation therapy for head and neck tumors].

The effect of radiation on the vestibular apparatus of animals and man have not been widely investigate. Referred symptoms are disequilibrium and spontaneous nystagmus in animals while histological features are intralabyrinthic haemorrhage, edema of the endolymphatic spaces and alterations of sensory hair cells. A group of 20 patients with head and neck cancer located in different sites (nasal cavity, oropharynx, oral cavity, parotid gland) underwent to vestibular investigations before and 3-6 months after radiation therapy. Ten patients (50%) showed an alteration of the vestibular function of peripheral origin after radiation treatment. Complications appeared from a few weeks up to several months following termination of radiotherapy. The slow development of the lesion permitted central compensation. Few patients had symptoms and vestibular symptomatology was always of secondary importance with respect to the initial pathology.


Ecoepidemiology of leishmaniases in Syria. 3. Leishmania major infection in Psammomys obesus provides clues to life history of the rodent and possible control measures.

Collections of Psammomys obesus from near Damascus, Syria in May 1990 and November 1991 contained animals of all ages. Both series had a high prevalence of Leishmania major infection. Lesions were small in November and large in May. Assuming the two collections were representative of typical years, it is inferred that the breeding season is between October and May: there is high winter mortality of animals born early in the breeding season, but high survival of their parents, and there is high mortality in summer of animals aged between 17 and around 20 months. Transmission in summer is, therefore, between old adults shortly before their death and young adults born in late winter or spring. Juvenile animals are not exposed to the infection. If these findings are confirmed it should be relatively easy to break this tenuous cycle.


Ivermectin in human onchocerciasis: a clinical-pathological study of skin lesions before and three days after treatment.

Findings are presented from an histological study of 360 skin-snips (from iliac crests, calves, ankles) taken from 30 Ivory Coast onchocerciasis patients before and three days after an oral dose of ivermectin (200 micrograms/kg). This dose causes a nearly complete disappearance of the intralymphatic microfilariae and, surprisingly, of the "extra-vascular" ones. That shows the difficulty to localize the microfilariae on histological sections; these microfilariae are in fact inside the lymphatic pre-capillaries. There was no intensification of acute skin lesions after the treatment, thus showing that, contrary to diethylcarbamazine (DEC), ivermectin does not induce an exit of microfilariae into the extralymphatic connective tissue. Under the influence of ivermectin, paralyzed microfilariae may be carried passively towards the deep sub-cutaneous lymphatics, and then destroyed inside the regional lymph nodes, without producing major changes in the skin.


[Human simuliidosis in France: antiquity, anthropophilic species].

The problem of the human Simuliidosis (caused by black flies) is reviewed for the France: important and, perhaps, relatively recent increase from the known human attacks by black flies. Countries and anthropophilic species are cited.


Engineering antibodies for therapy.

For most MAb-based therapies single doses of MAbs or MAb conjugates will not be curative. Rodent MAbs are highly immonogenic in almost all patients. The HAMA response abrogates efficacy and can cause toxicity in organs of clearance, especially for MAb-cytotoxic agent conjugates. Humanization is the most promising generally applicable approach to overcoming the immunogenicity of rodent MAbs. Chimerization reduces immunogenicity in patients significantly, but not completely. Full humanization of rodent antibodies with retention of most of their antigen binding activity is now a routine procedure. The studies with 4D5 (Kelley et al., 1992), however, illustrate that even when antigen binding activity is retained, humanization may affect the overall conformation of the antibody in ways which influence its interaction with cells (for example when the antigen is internalized or involved in signal transduction) and hence its in vivo properties. As yet there are not sufficient data to judge whether full humanization will (in practical terms) completely overcome the immunogenicity problem in patients, but these data will be available within a year. Antibody fragments are the most promising general approach to manipulating the pharmacokinetics and biodistribution of therapeutic MAbs. Such fragments are clearly superior to whole IgGs for tumour detection and will very likely prove superior for tumour therapy also. MAb targeting of highly potent cytotoxic agents to tumours represents a much-needed approach to improving therapeutic ratios in cancer treatment. Radioisotopes and highly potent low molecular weight drugs are the most promising cell-killing agents for MAb targeting, and conjugation technology suitable for clinical use of some of the best of these agents has now been developed. Very encouraging data have already been obtained in clinical studies of haematopoietic malignancies with MAb-isotope conjugates. Tumour loading data from clinical studies suggest that killing of solid tumours in patients will be achievable in the near future with repeated administration of humanized antibody fragments carrying the superior isotopes or highly potent drugs which are now available.


A study of RBC aggregation-sedimentation phenomenon with conductivity method.

In this paper, we present a conductivity method for measuring the RBC (red blood cell) aggregation-sedimentation phenomenon and the theoretical analysis of this phenomenon. A theory describing the RBC aggregation-sedimentation phenomenon with the conductivity method is proposed and the formula of the l-t function which depicts the RBC aggregation-sedimentation process is given. We put forward the aggregation index and sedimentation factor describing the RBC aggregation-sedimentation phenomenon for the first time.


Studies on transplantation of the laminin receptor and its roles in experimental metastasis of murine Lewis lung carcinoma cells.

The isolated laminin receptor (LN-R) labeled by 125I was reconstituted into liposomes. 125I-LN-R-liposomes and free 125I-LN-R were separated by Sepharose 4B column chromatography. The LN-R-liposomes showed affinity for laminin (LN) and were capable of binding to immobilized LN substrate. In order to make transplantation of LN-R, LN-R-liposomes were fused with cultured murine Lewis lung carcinoma cells with the help of polyethylene glycol (PEG) induction. The radiation with the fused cells was not removed by salt solution. The binding of the fused cells enriched in foreign LN-R to LN substrate increased by 87.5%. Furthermore, the murine Lewis lung carcinoma cells with and without transplanted LN-R were injected into C57BL/6J mice through tail veins (5 x 10(5) cells/each mouse) respectively. The mice in the test group died earlier than those in the control group. The total weight of lung tumor in the test group remarkably increased in comparison with those in the control group. The results taken together directly demonstrated that LN-R on carcinoma cell surface were involved in the recognition and binding of the cancer cells to LN in basement membranes, and also LN-R was of a crucial biological molecule in cancer metastasis.


[Re-discovery of yinzhou chaihu].

This paper deals with the distribution, original plant, course of rise and fall in drug market and quality of Yinzhou Chaihu, which was once regarded as a fine sort of Chinese drug Chaihu (Radix Bupleuri) in ancient times. Further research on this medicinal plant is suggested to facilitate its re-exploitation and utilization.


[Integrated control of pests injuring Chinese hawthorn Crataegus pinatifida Bge. var. major N.E.Br. by nonpollution techniques].

Field experiments on integrated control of pests injuring Chinese hawthorn by some nonpollution techniques including agricultural biological and physical methods, were carried out in Xinglong County, Hebei Province during 1989-1991. Satisfactory results were obtained. Compared with synthetic pesticides, the new techniques improve the control effect by 30%-60% generally, increase the number of natural enemies by 51.26%-68.51%, and enhance the yield by 47.58%. The test shows that the hawthorns from the field treated by the new techniques are either free of pesticide residual or with a residual 500-1000 times less than the residual standard fixed by FAO/WHO or the state.


[Preparation method and quality control of compound Daphne injection].

Compound Daphne Injection (CDI) is a sterilized solution extracted and refined from Cortex Daphnes, Radix Gentianae Macrophyllae, Radix Angelicae Pubescentis and Radix Notopterygii. The preparation method and quality control of CDI are discussed in this paper.


[Studies on dissolution of icariin from wuxian huichun capsules].

The accumulated dissolution of icariin from the traditional Chinese Wuxian Huichun capsules has been determined by roll-basket and three-wavelength UV spectrophotometry within 100 minutes. The values of T50 and Td for samples c, d are significantly greater than those for a, b. It is thus essential to determine the dissolution as a means to control the quality of capsules.


[Chemical constituents of Parthenocissus thomsonii (Laws.) Planch].

Five compounds (1-5) were isolated from the leaves of Parthenocissus thomsonii collected in Henan. On the basis of chemical reaction and spectroscopic studies, 1, 2 and 3 were identified as friedelin, epifriedelanol and quercetin respectively.


[Analysis of the volatile organic acids in 5 kinds of pericarpium Trichosanthis].

The volatile organic acids in the pericarps of Trichosanthes kirilowii, T. rosthornii, T. truncata, T. hupehensis and T. cucumeroides (Cucurbitaceae) were analyzed by methylation, GC and GC-MS-DS. The results showed that they were composed of fifteen long-chain fatty acids, such as palmitic, linolenic, linoleic, lauric, myristic acid, etc.


[Effects of tetramethylpyrazine and ferulic acid alone or combined on vascular smooth muscle, blood viscosity and toxicity].

The experiments showed that both tetramethylpyrazine and ferulic acid relaxed the norepinephrine-induced spasmodic contraction of rabbit and rat aorta strips, increased the coronary flow of isolated guinea pig hearts and reduced the whole blood viscosity in rats. Evaluated with Burgi's equation, the combined effect of these 2 drugs was obviously potentiated, but the combined acute toxicity in mice was greatly reduced.


[Effects of 3 Chinese medical prescriptions on alkaline reflux gastritis in rats].

The experimental alkaline reflux gastritis in rats was established after 9 weeks of anastomosis between stomach and jejunum. The experiment shows that xiangsha liujunzi decoction, xiaochaihu decoction and dahuang gancao decoction all help to inhibit edema, hyperamia and extravasted blood, as well as depress inflammatory infiltration and hyperplasia. The number of intestinal metaplasia in the group treated with xiangsha liujunzi decoction is decreased. All the three prescriptions are not able to lower the contents of bile acid in the stomach.


[Antiarrhythmic effects of crebanine].

Crebanine (Cre) iv 5 mg/kg could convert BaCl2-induced arrhythmia into sinus rhythm in rats, and could significantly increase the tolerant dose of aconitine to produce ventricular fibrillation (VF) and cardiac arrest (CA) in rats. The drug could also decrease the incidence of VF and CA by CaCl2 in rats and by chloroform in mice, but had no protective effects on ouabain-induced arrhythmias in guinea pigs.


[Effect of compound and minor prescription of heat-nature products radix Aconiti lateralis preparata, rhizoma Zingiberis and cortex Cinnamomi on the sympathetic nervous system, adrenal gland, TSH and LH].

The effect of compound and minor prescriptions of Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis and Cortex Cinnamomi on sympathetic nervous system, adrenal gland, TSH and LH of rats was studied. Results showed that both prescriptions made the heart rate quicken, estrous cycle shorten, improved the adrenal cortex hormone and promote TSH and LH synthesis and secretion. The two Heat-nature products (Radix Aconiti Praeparata and Rhizoma Zingiberis) may be used instead of all the three products to make a Heat Syndrome animal model.


[Experimental study of extracochlear electric stimulation].

The efficiency and feasibility of chronic extracochlear implantation and electric stimulation were studied in two adult cats and four 2-month kittens. The first electrode was placed on the round window by fixing the lead wire on the bridge of aditus between the middle ear and bulla cavity; the second electrode was placed on the surface of the tympanic promontory; the third was inserted into the temporal muscle out of the bulla and the forth fixed in transverse sinus with dental cement. ABRs and EABRs were recorded pre- and postoperatively and during electric stimulation. The results indicated that: (1) The chronic electric stimulation could be carried on with round window electrode; the fixation of round window electrode is satisfactory without the influence of postnatal skull growth. (2) EABRs evoked by electrically stimulating round window electrode were mainly generated by the auditory system, but its short response was partly generated by the vestibular system. (3) EABRs evoked by electric stimulation of round window electrode were contaminated by facial nerve response which could be inhibited by 2% xylocaine injection of foramen stylomastoid. (4) The EABRs evoked by stimulating tympanic promontory electrode is uncertain.


[Inner ear damage due to hyperlipidemia in the young and old guinea pigs].

Nineteen guinea pigs of one month and 11 of 30 months were given high fat diet for 3 months to produce hyperlipidemia; 16 of them followed by 3 months' normal diet to resume blood lipid level; 27 for control. The results showed that: The serum cholesterol level of the experimental groups was markedly elevated (P < 0.01) with fatty degeneration of liver. Damages in OHC, IHC, cells of stria vascularis and few myelin sheaths of cochlear nerve were seen in all experimental animals, and the reduction of cochlear damages was not seen in those animals with blood lipid level resumed to normal. Auditory dysfunction was very marked as shown by ABR in the old animals with hyperlipidemia as compared with controls (P < 0.01).


[Auditory middle latency response: a study of optimal measuring conditions and determination of normal values].

The purposes of the present study were to select the optimal conditions for middle latency response (MLR) measuring with a statistical model of orthogonal test, and to determine the normal values of MLR. It showed that stimuli click and logon of different frequencies could be used to evoke MLR. The filter-setting was a significant factor in effecting the measurement of MLR. 30-50Hz or 30-100Hz was the most optimal filter-band. The effects of stimulus polarities on MLR bore no significant difference statistically. In clinical practice, stimulus repetition rate of 11/s was most desirable. We determined that mean thresholds of MLR were approximately 10dBnHL and latencies of wave Po, Na and Pa were approximately 10, 20 and 30ms respectively. The amplitudes of MLR varied greatly.


[Electron microscopic observation on benign tumors of the facial nerve].

Two cases of benign tumors of the facial nerve were examined. One was neurilemmoma and the other neurofibroma. The histopathological diagnoses of the tumors are difficult to make with light microscope. However, electron microscopy may be helpful. Under transmission electron microscope, the difference of two kinds of tumors is obvious. The main pathological features had been discussed.


[Surgical treatment of cancer of the base of the tongue and epiglottis].

This paper reports the surgical treatment of 10 cases of cancer of the base of the tongue and the epiglottis resected by a translaryngeal approach. In addition, a brief description of the technique is introduced. All patients had squamous cell cancer which was obviously advanced to stage IV and the tumor mass had extended to the whole root of the tongue, the vallecula and the epiglottis. After operation, all patients learned to swallow effectively and no persistent aspiration occurred. The speech articulation was satisfactory. Postoperative follow-up of all the patients, the shortest being 13 months, revealed no local or cervical lymphatic recurrence, but two patients died of lung metastasis, one after 18 months and the other after 48 months. The translaryngeal approach maintains the integrity of the mandibular and occlusal joints, avoids deformity to the face and the anterior oral cavity and prevents scarring in those tissues affording maximal mobility of the tongue.


[Laryngeal carcinoma with laryngeal abscess].

We had encountered 5 cases of laryngeal carcinoma associated with abscess. Four of them were advanced laryngeal cancer with abscess induced by mechanical injury, and one with post-radiation laryngeal perichondritis & abscess formation. Management included total laryngectomy in 3 patients, partial laryngectomy in 1 patient, and resection of post-radiation abscess in one. Laryngeal abscesses are seen rarely today. Endeavour should be made to decrease such complication. The authors had presented their experience in the management of laryngeal carcinoma associated with laryngeal abscess, together with a review of the history and some of the current ideas about this problem.


[Langerhans cells in laryngeal carcinoma in relation to prognosis].

Infiltration of Langerhans cells (LCs) was investigated by immunohistochemical methods with the use of anti-S100 protein in 25 cases of stage II and 50 cases of stage III laryngeal carcinoma. Varying population densities of S100 positive LCs were noted. LCs were mainly interspersed among the tumor cells. The prognosis of patients with stage II and stage III laryngeal carcinoma correlated well to the density of LCs in tumor tissue in patients with a marked infiltration of LCs, survival time was longer than in those cases with only a slight infiltration (P < 0.05). This indicates that LCs may play an important role in the immunologic defense mechanisms of the host against the tumor in laryngeal carcinoma.


A brief history of ocular toxicology.

The background leading to the need for ocular toxicity testing is reviewed. Awareness of side effects of various categories of drugs (e.g., steroids and cataracts) has provided impetus for examination of many categories of compounds including ocular drugs, cosmetics and household chemicals. The standard test (Draize) used for many years in the evaluation of ocular toxicity of many chemicals is being modified or replaced by other procedures. Modifications include volume and/or concentration reductions. Replacements include the use of in vitro systems of either freshly isolated tissues, tissue cultured cells, or non-living systems. The relative predictability of each approach is evaluated with the conclusion that only in vivo testing (albeit using low doses and low volumes) can reflect the full spectrum of potential responses. Each in vitro methodology has at least one drawback relative to in vivo test procedures.


Status of in vitro ocular irritation testing.

This paper reviews advances in the validation of alternative methods for eye irritation testing since the 1987 publication, A Critical Evaluation of Alternatives to Acute Ocular Irritation Testing (1). We have highlighted details of methods that appear promising and identified the minimum needs and endpoints necessary to develop a battery or batteries of in vitro tests to evaluate eye irritancy. We have recommended a series of workshops to provide identified batteries for specific classes of chemicals or for specific uses of eye irritancy testing. We have also identified the need for consensus meetings and peer-reviewed publication to ensure that the most predictive batteries become parts of validation studies. Finally, we note that academic scientists, industry, government and the animal protection community must work together in order to replace in vivo eye irritancy testing with appropriately validated in vitro methods.


Action potential response of the corneal nerves to irritants.

The cornea, in addition to its refractive function for the eye, and by way of its very dense sensory innervation, serves a very important protective function for the visual organ. The cornea receives mainly sensory innervation from the first division of the trigeminal ganglion and a sparse amount of sympathetic fibers. The sensory nerves carry out their protective function by responding to various types of stimuli in a way so that they are all perceived psychologically as painful. Neurophysiological data indicates that, despite the morphological similarity of free-nerve endings in the cornea, they are differentiated functionally. A concentration series, (0.005 to 10% solution in saline), of various potential irritants (phosphate detergent, baby shampoo, liquid chlorine bleach, herbal shampoo, onion juice, SDS, and sodium chloride) was applied directly to the cornea of the anesthetized rabbit. Neural activity was assessed from extra-cellular records of long ciliary nerve over a ten second application period, and for ten seconds following stimulus removal. Baby shampoo was non-stimulatory over the applied concentration range. Sodium chloride, on the other hand, exhibited linear response dynamics over the range of 0.01 to 5% (p < 0.001). SDS was highly stimulatory, but showed no predictable concentration or response relationship. All of the other irritants tested responded in a logarithmic fashion. This suggests that the application of neurophysiological techniques to assess the pain and potential inflammatory aspects of a substance for human use can be monitored in this fashion. Moreover, response profiles for various classes of compounds and homologous series, as well as pH and osmolality, can be established.


Utilization of biomacromolecular in vitro assay systems in the prediction of in vivo toxic responses.

Target biomacromolecular assay systems utilize as endpoints quantifiable alterations in key macromolecules elicited by various chemicals and formulations. The EYTEX Assay System, an example of a target biomacromolecular test method, has been used to predict the in vivo ocular irritancy potential of chemicals and formulations. The biomacromolecular reagent is a standardized matrix which can be produced routinely. One hundred test chemicals, representing diverse chemical classes with a wide range of toxic responses in vivo, were evaluated in the EYTEX system. In vitro results were compared to maximum 24-hour Draize scores and Draize classifications. The concordance of the in vitro and in vivo results demonstrated the relevance of the alteration of the EYTEX macromolecular matrix to the prediction of in vivo ocular irritation. The relevance of the in vitro endpoint of turbidity of the EYTEX matrix to in vivo ocular irritation has thus been demonstrated for a large number of test agents in other evaluation studies (1, 2, 3, 4, 5, 6, 7, 8). Integration of macromolecular-based test methods with in vitro cytotoxicity or cellular response methods may provide complementary information about mechanisms of target-induced toxicity. The target biomacromolecular assay systems which provide standardized, reproducible reagents are valuable components of test batteries.


In vitro methods: their relevance and complementarity in ocular safety assessment.

Ocular irritation includes a wide variety of mechanisms some of which can be explored by in vitro methods. For example, the effects on epithelial cells that constitute the outer layers of both the conjunctiva and the cornea may result in direct cytotoxicity or impairment of cellular functions -such as impermeability-, phenomena that can be explored in vitro. Irritancy may also involve inflammation of the conjunctival connective tissue and of the corneal stroma with its vascular and cellular features; effects on the stroma can lead to the opacification of the cornea; this last phenomenon may be the consequence of mechanisms such as modification of the structure of proteins or changes in stroma hydration which in particular is closely related to corneal endothelium metabolic activity. Recovery after eye injury depends partly on the extent of ocular damage and on the residual mitotic activity of the remaining cells. We have studied 41 surfactants, lotions and shampoos in 6 to 8 in vitro methods each one exploring one or two endpoints that could be linked to the ocular irritancy phenomena described above. In vivo ocular irritancy data for these materials from previous studies were compared to in vitro results. The results obtained show that -among the techniques that were investigated and for the categories of substances that were studied- the Het-CAM test and more particularly the endpoint that is related to vascular effects gives the best assessment of acute ocular irritancy (Spearman's rho coefficients between in vivo and in vitro data greater than 0.90); however, cell culture methods, especially one based on short contact time between cells and products and on evaluation of early toxic effects, also proved interesting (Spearman's rho coefficients between in vivo and in vitro data greater than 0.85). Moreover, the isolated cornea opacity and permeability test gave complementary information more related to recovery from surfactant-induced damage. These encouraging results lead us to consider in vitro ocular safety assessment with optimism for the categories of products investigated.


Alternatives to ocular irritation testing in animals.

The preliminary conclusions of a survey of possible non-animal alternatives to the Draize rabbit eye irritancy test, recently conducted for the Commission of the European Communities, are presented. The various types of alternatives to animal tests are reviewed in terms of their current state of development and validation, and also their potential in relation to the type of exposure, level of testing, type of testing, type of effect, location of effect, and type of test material. Various problems concerning the availability and quality of in vivo eye irritation data, and the use of this data in in vitro/in vivo comparisons, are highlighted. Finally, the use of step-wise and integrated animal/non-animal and non-animal/non-animal test systems and strategies are discussed.


The status of eye irritancy testing: a regulatory perspective.

Eye irritation testing is a salient public issue and continues to escalate on the public agenda. Issues relevant to this milieu include legislative proposals to ban animal use for cosmetic testing, adequacy of the current standard (viz., the Draize Eye Irritancy Test), availability of non-animal methodologies, validation paradigm for new testing models, international harmonization of testing standards and methods, and the regulatory role in product testing and enforcement. The Food and Drug Administration (FDA) feels that enactment of legislation proposed to ban animal use from testing products for safety would pose serious problems from a public health perspective. FDA encourages the development of alternative test methods and is aware that many such tests are in various stages of evolution. At this time, however, none of these tests has been accepted by the scientific community as total replacement to the Draize test. FDA's basic positions on the use of non-animal alternatives are as follows: 1) The use of animal tests by industry to establish the safety of regulated products is necessary to minimize the risks from such products to humans, 2) The Draize eye irritancy test is currently the most valuable and reliable method for evaluating the hazard or safety of a substance introduced into or around the human eye, and 3) No non-animal tests are presently available to completely replace the Draize. FDA is actively involved with U.S. and international groups to harmonize protocols for product development, evaluate the current status of non-whole animal methodologies, and standardize testing requirements. The Agency has recently participated in several scientific symposia evaluating the status of non-whole animal methods in toxicity testing. Moreover, FDA representatives are currently scheduled to participate in international meetings and workshops planned for the immediate future addressing several issues in product safety determination.


In vivo assessment of corneal stromal toxicity by tandem scanning confocal microscopy.

Epithelial wound closure following superficial corneal abrasions precipitates a complex series of cellular changes in the stroma. Transmission electron microscopy and light microscopy have demonstrated that keratocytes in the anterior stroma show prominent cytoplasmic process and granularity within an hour after this injury. Cell degeneration follows rapidly, with almost complete depletion of these keratocytes by 6-12 hours. Regeneration then occurs by 24-48 hours. These findings were confirmed in-vivo by tandem-scanning confocal light microscopy in rabbits. The optical sectioning capability of this instrument allowed us to demonstrate the three-dimensional array of fibroblast process, their subsequent condensation, and loss by sequential examinations on the same animals. Cell shrinkage and other fixation artifacts common in corneal histological sections were avoided by this technique. Using this method, we investigated the corneal cytotoxicity of an antimitotic agent, mitomycin-C and a muscarinic antagonist, atropine sulphate. Mitomycin-C, an antimetabolite used in pterygium treatment, led to irreversible keratocyte depletion even after four days of observation. However, cellular reaction to the wound were attenuated by atropine sulphate suggesting that it may be useful as a novel inhibitor of fibroblast proliferation.


In vivo MRI and fluorescence studies on the ocular lens.

During the past two decades progress in biophysical technology has made it possible to monitor aging and pre-cataractous as well as cataractous changes in the ocular lens in vivo as well as in vitro. Because they are non-invasive these techniques can be performed in vivo and utilized as screening methods to detect and predict eventual lens opacification, and they should also provide increasingly important information to help clarify the cataractogenic process. Three such biophysical approaches can now be employed in vivo; these include lens fluorescence, light scattering measurements and magnetic resonance imaging (MRI) T2 analyses (1-27). We have utilized two of these methods (fluorescence spectroscopy and MRI measurements of lens water [T2] phases) to delineate normal age-related and pre-cataractous changes in a series of human subjects and in patients with early lens opacities. The parameters employed for these studies were based on data accumulated from in vitro experiments on human lenses and in vivo and in vitro data from animal experiments (2, 6-8, 18, 19, 22, 25-27).


Quantification of blood-aqueous barrier function using laser flare measurement and fluorophotometry--a comparative study.

Fluorophotometry allows calculation of the permeability coefficient k(a) of the blood-aqueous barrier to fluoresceine after i.v. dye application; aqueous flare can be graded objectively by laser flare measurement and permits in vivo estimation of over-all protein concentration in the aqueous humor. To evaluate a formal relationship between both procedures we performed laser flare measurements on 40 eyes (clinically ranged from healthy to mild uveitis) before and during fluorophotometry. Laser flare count [mec-1] raises exponentially (r = 0.8; p = 0.05) with an increasing permeability coefficient to fluoresceine k(a) [10(-4)min-1]. Laser flare count during the fluorophotometry procedure is not increased (p = 0.05) compared to the prescan. Reproducability was 14% +/- 7.5% for laser flare measurements and 13% +/- 5% for fluorophotometry. Malfunction of the blood aqueous barrier possibly increases the permeability to molecules of high molecular weight not proportional to that of hydrophilic particles of low molecular weight. The exponential regression between the data achieved with both procedures suggests that fluorophotometry is more sensitive in detecting early changes in blood aqueous barrier function whereas laser flare detection could be appropriate in more severe cases of barrier dysfunction.


Comparative investigations on the cataractogenic effect of a triazin-derivative in albino and pigmented rats: II. Effects documented by Scheimpflug photography.

A Triazin-derivative from a group of industrial chemicals was found to cause cataracts in albino rats during a subchronic toxicity study. To get more insight into this effect, a study was designed with 20 albino (Wistar) and 40 pigmented (black-hooded FB 30) rats using different dosages of the test compound. In a 3 months study period, all rats were photographed with a Scheimpflug camera TOPCON SL-45 3 times, at a baseline examination, prior to any treatment, in the middle and at the end of the study period, prior to sacrifice. The black-and-white film (Kodak T-Max 400R) was standardly developed and evaluated with a Joyce-Loebl microdensitometer in 3 regions of the lens, the capsule, the cortex and the nucleus. The density data from the second and third examination clearly demonstrate that cataract development in the albino rats takes place in the cortical region, whereas in the pigmented rats it takes place in the cortical and partly in the nuclear region. In addition, one albino and two pigmented animals of the groups investigated developed bilateral mature cataracts. Differences in cataract morphology between albino and pigmented rats are presented by Eiben and Wegener (1). The results underline the importance of toxicity testings in pigmented rats, they evidence that the data derived solely from albino animals can be misleading.


Overview of the corneal toxicity of surgical solutions and drugs: and clinical concepts in corneal edema.

Surgical solutions and drugs are important in ocular surgery. These include irrigating solutions, viscoelastic substances, mydriatics and miotics, and a growing number of other agents designed to enhance intraocular surgery and its outcome. Potential for damage to the corneal endothelium and other tissues is related to the chemical composition, pH, and osmolality of the irrigating solutions that bathe tissues. Quality balanced salt solutions (BSS) are usually safe for use as an intraocular solution in patients with normal corneal endothelium. If prolonged irrigation times are expected, or the patient already has decompensated endothelium, i.e., primary or secondary endotheliopathy, the use of a "complete" BSS solution is indicated to minimize damage. Intraocular sulfite-containing epinephrine may cause severe corneal edema and should be avoided, or if used, be well diluted. Sulfite-free epinephrine solution is now available and does not cause the endothelial toxicity that one may see with sulfite-containing epinephrine solutions. Current formulations of acetylcholine and carbachol used as miotics in surgery have been evaluated in humans and caution is recommended in using acetylcholine solutions intracamerally in patients with already decompensated endothelium. Chondroitin sulfate, hydroxypropyl methylcellulose, and sodium hyaluronate are non-toxic to animal endothelial cells under conditions analogous to cataract extraction in humans but can be toxic to endothelium if there is continued contact with endothelium for hours. Chondroitin sulfate has been shown to have more of a protective effect in mechanical pseudophakos trauma probably because of its cohesiveness and tendency to coat the endothelium. Viscoelastics cause a significant rise in intraocular pressure of > 30 mm Hg in 3-10% of patients. Very high intraocular pressures are often seen postoperatively after viscoelastic use surgically in patients who preoperatively have a history of ocular hypertension or glaucoma.


The role of viscoelastics, cannulas, and irrigating solution additives in post-cataract surgery corneal edema: a brief review.

Corneal clarity is dependent upon maintenance of the corneal endothelial barrier and pump. Mechanical trauma is usually considered to be the most significant factor in corneal endothelial damage during cataract surgery resulting in postoperative corneal edema. However, corneal decompensation out of proportion to the degree of trauma seen during surgery does occur. These cases of unexpected corneal edema can often be traced to unrecognized preoperative endothelial dysfunction or to toxicity of intraocular medications used during surgery. This paper reviews the role of viscoelastics in reducing surgical trauma, their toxicity, and the risks of toxicity inherent in the use of re-usable cannulas and irrigating solution additives. Disposable cannulas should be used whenever possible. The use of re-usable cannulas with viscoelastics is highly likely to result in toxic residues being introduced onto the eye, and must be avoided. Irrigating solution additives should be tested with in-vitro human donor cornea perfusions prior to clinical use.


Cytotoxicity of ophthalmic preservatives on human corneal epithelium.

Because the corneal epithelium invariably encounters the full concentration of the preservative that is contained in multi-dose topical ophthalmic preparations, we investigated the cytotoxicity of several of these agents by using a sensitive model of human corneal epithelial cells in vitro. Primary cultures of epithelial cells were prepared from freshly enucleated globes. At confluence, all experimental cultures received a single dose of preservative at the concentration present in marketed formulations. The serum in the culture medium simulated the possible neutralizing effect of proteins present in the tear film in vivo. The cells were observed continuously by phase-contrast microscopy and time-lapse videomicrography for 24 hrs. Benzalkonium chloride at a concentration of 0.01% and chlorobutanol at 0.5% caused immediate cell retraction, as well as cessation of normal cytokinesis, cell movement, and mitotic activity; the epithelial cells degenerated within 2 hrs and 8 hrs, respectively. Cultures treated with chlorobutanol developed conspicuous blebs on the cell surface after 3 to 5 hrs of exposure. Thimerosal (0.001%) caused cell retraction, cessation of mitotic activity, and total cell destruction within 9 hrs. Sorbic acid (0.1% and 0.2%) greatly reduced cell movement and suppressed mitotic activity, but no cell death occurred. At concentrations of 50 ppm and 30 ppm, H2O2 instantaneously caused a marked retraction of the cells, followed by cessation of cytokinesis, cell movement, and mitosis. Retraction and death of the epithelial cells occurred within 12-24 hrs after exposure to 1 ppm H2O2 in serum-free medium. Polyquaternium ammonium chloride (0.001%) and polyaminopropyl biguanide (0.00005%) had no discernible effects on cytokinetic movement or on the mitotic activity of the epithelial cells. We relate our findings in vitro to those reported in vivo and discuss the mechanism of cytotoxicity of the various preservatives.


Assessing the biostability of intraocular lenses.

This manuscript represents an attempt to evaluate the methods used to assess the biostability of IOLs, in particular their leaching characteristics, the effects of laser pitting, their tensile strength and the effects of UV irradiation on long term implantation of IOLs. The literature relating to these topics during the last two decades has been reviewed and experimental study protocols are presented.


Cytogenetic assays for genotoxic agents.

The induction of genetic damage has clear and dramatic implications for human health, with teratogenic, mutagenic, cataractogenic and carcinogenic consequences resulting from cellular chromosomal alterations in appropriate tissues. When analysing the potential of an agent to initiate genetic damage or in evaluating possible incumbent genomic damage a variety of complementary assays may be employed. These apply to cells in vitro, to in vivo assessments involving small mammals and most importantly to derived human cells and tissues including those of ocular origin. Cytogenetic assays have the important advantage that they enumerate damage at the level of the individual cell. Assays involving the examination of chromosomal aberrations at mitosis, of cells prior to mitosis using the technique of premature chromosome condensation, of micronuclei in post-mitotic cells and of sister chromatid exchanges will be described. The development of human chromosome specific probes and fluorescent in situ hybridisation (FISH) techniques combine the resolution of molecular biology with classical cytogenetics in a powerful approach to defining genomic change and its consequences. These techniques and assays can be further augmented by in situ cytometry such that overall a number of parameters can be quantified involving cellular kinetics, clastogen and/or aneugen definition and ultimately the establishment of dose response relationships. A rational basis for avoidance or control, for intervention or for defining probable cause of the role of genotoxicants in the development of human disease can then be established.


Ocular side effects of accutane therapy.

The recent interest in treating acne with one of the retinoid drugs has been accompanied by a wide variety of ocular side effects involving the eyelids, cornea, lens, optic nerve and retina. In one group of patients being evaluated for possible efficacy of a retinoic acid analogue in treating psoriasis, several patients complained of difficulty driving at night due to decreased dark adaptation which we were able to document. Fortunately, most of the above side effects tend to disappear within months after the drug is discontinued. However, we have recently seen two cases of dry eye syndrome associated with Accutane therapy that have persisted for more than two years. In addition, scattered reports have appeared regarding cataracts in young patients (teens to early 40's) which developed during, and/or after Accutane treatment. We have examined lens matter derived from two such patients who had extracapsular cataract extractions. Their lens proteins showed an elevation in UV absorptivity (between 330-390 nm) compared with matched control material (derived from Eye Bank specimens) and HPLC analyses demonstrated an abnormal peak in their profiles which was similar to one present in control samples incubated with retinoic acid and was not present in lens protein samples derived from cataracts not associated with Accutance therapy. These observations demonstrate that some of the Accutane induced ocular side affects are not reversible when the drug is stopped, and patients on such therapy should be carefully monitored.


Ocular toxicity of subconjunctival gentamicin.

The subconjunctival injection of commercial gentamicin, given either as a single dose or as repeated injections, caused a hyperemic conjunctival response. Simultaneously there was a toxic myopathy induced in the extraocular muscles. The overall response, followed with light microscopy, occurred as a focal infiltrate of polymorphonuclear leukocytes with progression over a few days to a mononuclear cell infiltrate that accompanied fiber degeneration. Injections of each ingredient of commercial gentamicin individually showed that only gentamicin caused the muscle response; methylparaben, EDTA, and sodium bisulfite were without effect. The pH of the solution was eliminated as a contributing factor as was osmolarity of the injection. Increasing recognition is being given to post-operative complications caused by the prophylactic subconjunctival injection of gentamicin following cataract, and other intraocular surgery. The present data offer a mechanistic explanation for many of these toxic findings.


Cataract in renal transplantation recipients with combination ciclosporin treatment.

Post surgical cataracts induced by corticosteroids as immunosuppressive agents were investigated in recipients undergoing triple therapy with ciclosporin and the results were compared with those who had therapy without ciclosporin administration. The subjects of the triple therapy group were 54 cases with a mean age of 31.7 years. The mean observation period was 25 months. The incidence of posterior subcapsular cataract was 77.8%. 7.9% of them developed progressed cataract. Early cataractous changes were noticed within one post-operative year in half of the cases. 3 out of 22 cases that were followed up over three years showed progressed cataractous changes. The total doses of methylprednisolone during the period of the first post-transplant year in recipients with Grades I or II and over Grade III were 7.7 +/- 1.9g and 9.8 +/- 3.6g, respectively. They were significantly higher than those in the conventional therapy group. However, a 2 to 3 g reduction in the total dose of steroids during the first year had no influence on cataract occurrence.


Ocular toxicity of prednisone in pediatric patients with inflammatory bowel disease.

We performed ocular examinations on 58 corticosteroid-treated pediatric patients with inflammatory bowel disease (IBD) and on 58 age-matched controls. Posterior subcapsular cataracts (PSC) were detected in 12 of the 58 treated patients (20.7%) and in none of the controls. The difference in mean intraocular pressure (IOP) between the treated patients (15.89 +/- 4.11 mm Hg) and control subjects (13.63 +/- 2.35 mm Hg) was significant statistically (P < 0.001). Twenty-one patients (36.2%) were characterized as "IOP responders" (IOP > or = 20 mm Hg, change in IOP > or = 6 mm Hg between visits, or a difference in IOP > or = 6 mm Hg between the two eyes). Formation of PSC was not correlated significantly (P > 0.05) with the total dose of prednisone, duration of treatment, average daily dose, or number of days on high doses (> or = 25 mg). Raised IOP was correlated (P = 0.005) only with average daily dose (12.4 +/- 10.9 mg/day; range, 0-47 mg/day) 30 days before examination. When the dose of corticosteroid was reduced to < 10 mg/day, 2 patients manifested regression of PSC, and 12 IOP responders showed a decrease in IOP to within 2 SD of the mean control IOP. Only 3 of the 58 treated patients (5.2%) manifested both PSC and raised IOP. A significant inverse correlation (P = 0.02) was established between IOP at first examination and formation of PSC. We propose that the mechanisms for steroid-induced lens opacities and raised IOP do not share the same genetic basis. Because 52% of these children developed either PSC or raised IOP with prednisone therapy, we advocate careful ophthalmologic monitoring of pediatric patients receiving corticosteroids for IBD or any other condition.


Effect of intravitreal injection of norfloxacin on the retina in pigmented rabbits.

The effect of an intravitreal injection of norfloxacin on the retina was evaluated by in-vivo electroretinogram (ERG) and histological examination in pigmented rabbits. The intraocular pharmacokinetics after an intravitreal injection of norfloxacin were also investigated. An intravitreal injection of 50 micrograms norfloxacin produced no significant change in the ERG. An injection of 500 micrograms norfloxacin decreased the amplitude of the oscillatory potentials, and delayed their peak latencies 3 hours after the injection, but these changes recovered within 7 days. A marked suppression of the c-wave was noted in one pigmented rabbit. Neither 50 micrograms nor 500 micrograms norfloxacin caused any apparent changes in the visual evoked potential and in the retinal histology 7 days after the injection. The intraocular pharmacokinetic study showed that the concentration of norfloxacin in the choroid-retina was almost the same level as that in the vitreous body 3 hours after the injection. However, the former was higher than the latter 7 days after the injection, suggesting the persistency of norfloxacin in the choroid-retina. An intravitreal injection of 50 micrograms norfloxacin could be used without retinal toxicity. A high dose-intravitreal use of norfloxacin needs careful attention with respects to its persistency in the pigmented ocular tissues.


Effect of Gingko biloba extract (EGb 761) on chloroquine induced retinal alterations.

Electroretinography was used to investigate the preventive action of Ginkgo biloba extract (EGb 761) in experimental chloroquine-induced retinopathy in rats. EGb 761 contains flavones and anthocyanosides known for their oxygenated radical scavenging properties. Chronic administration of chloroquine (20 days) caused an overall lengthening of the duration of the ERG b-wave, together with delayed peaking. These anomalies became more marked with increased duration of treatment. In rats treated simultaneously with chloroquine and EGb 761 no such modification of the electroretinogram (ERG) was observed. These results suggest that retinal toxicity may be related to a localized inflammation releasing oxygenated free radicals and/or PAF. EGb 761 may thus afford a useful preventive treatment for chloroquine-induced retinopathy, and generally for xenobiotic retinotoxicities.


Inhibition of vincristine-induced retinal impairments by a specific PAF antagonist.

The alkaloid vincristine is widely used for its anti-leukemic and anti-tumor activity. However, the drug also displays considerable toxicity, particularly for the retina. Indeed, vincristine has been shown to induce alteration of photoreceptor outer segments in animals and impairment of scotopic vision in man. This type of retinopathy is an inflammatory disease in which PAF may be implicated and for which specific PAF antagonist may have a therapeutic role. Thus, we measured the effects of a new hetrapezine derived PAF antagonist, BN 50730, on a vincristine-induced retinopathy in the rat. Retinal impairments were established by recording several parameters of the electroretinogram (ERG) obtained from isolated retina. Our results indicate that, first, the increase in PIII duration induced by vincristine is significantly reduced by BN 50730 administration and, second, the decrease in the value of the PIII/b wave ratio caused by vincristine is partially inhibited by treatment with BN 50730. These experiments suggest that PAF is implicated in vincristine retinopathy and demonstrate the therapeutic effect of a specific antagonist of the mediator.


Intraocular penetration and effect on the retina of fluconazole.

The intraocular concentration of fluconazole was measured in nonvitrectomized and vitrectomized eyes after an intravenous administration of 5 or 25 mg/kg fluconazole in albino rabbits. Respective fluconazole concentrations in the aqueous, vitreous and serum 1 hour after administration were 2.87, 1.72 and 4.60 micrograms/ml at 5 mg/kg administration, and 14.93, 7.05 and 20.63 micrograms/ml at 25 mg/kg administration, indicating high and dose-dependent intraocular penetration of fluconazole. Intraocular penetration of intravenously administered fluconazole was moderately, not very much, enhanced by vitrectomy. The in-vitro electroretinogram (ERG) remained unchanged after perfusion with 20 micrograms/ml of fluconazole. The in-vivo ERG and the visual evoked potential was unchanged after the daily administration of 25 mg/kg fluconazole for 8 days. The toxicity of fluconazole on the retina would be low and within safety limits so far as it is used at clinical dosage. Fluconazole may have a place in the treatment of fungal ocular infections.


A new approach to drug penetration study.

To investigate the route of drug penetration into the eye and drug distribution patterns in the lens, the distribution of aldose reductase inhibitor (AL-04114) in the lens was measured in short term bovine lens organ cultures and topical administration to rabbit eyes. A micro lens sectioning technique was applied to determine drug localization within the lens. Freshly enucleated bovine lenses were incubated with different concentrations of an ARI (AL-04114)-containing medium for 3 hours. For the in vivo study, 40 microliters of 0.3% AL-04114 (ophthalmic solution) were administered into the cul de sacs of rabbits 3 times at 3 hour intervals. After the incubation and final instillation, the lenses were divided into an equatorial ring and several layered sections. Drug concentration was measured by a reversed-phase HPLC system. The drug concentration was highest within the layer of the posterior shallow cortex > equator > anterior shallow cortex. No drug penetration was observed in the anterior/posterior deeper cortex or nucleus in vitro. The in vivo experiment revealed drug penetration in the equator and anterior shallow cortex, but not in any other lens layers. Drug penetration was detected within the serum and aqueous humor, but not in the vitreous.


[The biological aspects of botfly invasions in reindeer].

Field and laboratory studies established the development time of all the phases of Oedemagena tarandi and Cephenemyia trompe in different climatic zones of their habitat. The phenological and ecological features of O. tarandi and C. trompe in the aforesaid zones were identified which are the basis for scientifically grounded prophylactic measures. Data on potential and actual fecundity make it possible to calculate their reproduction potential and to forecast the invasion intensity of the reindeer in the next season.


[The action on brain functions in white rats of the immunostimulant Freund's complete adjuvant].

The effect of immunostimulator--Freund's adjuvant complete on the nociception and learning of white rats using food-obtaining and avoidance of electric shock techniques has been studied. It has been shown that the adjuvant in doses for active immunization causes itself the expressed changes in animal behaviour. The adjuvant's injections significantly increases the learning ability of animals both with negative and positive reinforcement as compared with control one. The changes in pain severity is marked only for dose 0.2 ml. The nonspecific action of adjuvant should be taken into account in researches which use the active immunisation method.


[Problematic situations of intercultural misunderstanding in social services].

This article discusses research on the difficulties of practising social work in a multicultural and multiethnic context. The research is based on critical incidents that were experienced by 40 social workers in "the most ethnic" public social service centres of the Montréal region in 1990-1992. The most significant culture shocks that occurred between workers of a developed Western-type society and clients from developing, non-Western societies relate to a different notion of the role of social services, to different methods et educating children, to unequal relationship between men and women, to a different notion of family and to a different notion of physical and mental health. The authors emphasize that a better understanding of these shocks and an effort to identify and analyze these sensitive zones of intercultural encounter can have a definite impact on the practice and training of social workers.


[Ethnicity and insanity: the many faces of abnormality].

This article suggests that the notion of madness varies with the social context, the dominating values of each cultural community and the position given to agents and social workers in the field and in the hierarchy of knowledge. As an interplay of representations and cognitive strategies, madness can be considered as a "symptom" of the "normative" and "reductive" biases of each era, but also as a revealing trait of the sensibility of each culture toward certain dimensions of unusual experiences. Following a review of the magical, prophetic, theological, moral, pathological and analytical versions of madness, the author concludes by emphasizing the necessity of always taking into consideration the cultural standpoint that characterizes the experience of madness as much as it does its study.


[Ethnic relations and identity-based tensions in a multicultural context].

Since the beginning of the 80s, Montréal's population of non French--and non English-speaking inhabitants has increased rapidly, especially in schools (estimates show that by the year 2000, this segment will represent about 50% of students). In addition, this population of diverse origins is composed of only a minority of Europeans; Caribbeans and Orientals make up the vast majority of immigrants that have settled in Montréal over the last decade. How does this unique mix of cultural backgrounds impact on the perception that these youth from multiethnic neighbourhoods have of their own culture and social relations? This is the basic issue that the authors have attempted to solve in the course of their research. The authors focused particularly on the identity-based tensions that stem from interaction between youth and the strategies they develop to overcome these tensions.


[A pathogenic manpower program: the program for foreign domestics].

Every year, a special federal program arranges for the arrival of about 12,000 educated women to Canada to work several years in private homes as housekeepers. However, in order to meet the needs of the employer and the Canadian economy, these women are denied their fundamental freedoms and are deliberately kept in a precarious situation material and psychologically and with respect to their status. Because it exposes these female workers to such factors of instability and to the negative effects of key experiences, this program carries the seed of mental illness.


[Training is not always a quick solution].

This article examines the training strategy developed in 1990 by the Table de concertation des Organismes de Montréal au service des Réfugiés, which was designed for social workers employed by non governmental organizations who were offering new arrivals a variety of support services to help them establish themselves and integrate. The term "new arrivals" includes immigrants and refugees, and takes into account the fact that members of communities that have been established in Québec for a longer period of time may still be using these services. The social workers of these organizations work on a permanent, temporary, internship or volunteer basis. Their work covers a wide variety of areas: assistance in finding lodging and furniture, held in meeting the requirements of immigration services, information on various public services (schools, health and social services, etc.) and referrals to appropriate specialized services. In short, the intervention of community social workers is characterized by versatility and diversity. In his article, the author uses the term "intervenant" to describe these social workers. The training strategy under study aims to facilitate communication and contacts between protagonists that do not necessarily share the same values, nor the same world vision.


[Parental stress in mothers of preschool children: validation and Quebec norms for the Parental Stress Inventory].

The authors examine the metrological qualities of a French version of the Parenting Stress Index (Abidin, 1983; Loyd and Abidin, 1985) based on a sampling of 122 Québec mothers with a preschool child. Results show that the Parental Stress Inventory presents internal consistency indices that are equivalent to those obtained in the U.S. sampling. However, the samplings differ on seven out of 13 subscales, as well as concerning the scores obtained for the child's realm and the overall stress, Québec mothers show higher scores. The factorial analysis of the subscales supports the existence of a hierarchical structure composed of a general factor of parental stress and two specific factors: the realm of the child and the realm of the parent. The score relative to the realm of the parent varies according to the socioeconomic level and the marital status of the mother. The mother's age is negatively correlated with the score of the child's realm. The child's aggressiveness/hyperactivity level, as perceived by the teacher in a class situation, is positively correlated with the score of the subscale Difficulty to accept the child's characteristics and the subscale Distraction and hyperactivity of the child. The authors present benchmarks that were developed in order to take into account the noted differences between the Québec and U.S. samplings.


[Support provided by third parties and the reaction of close female caregivers in the care of elderly persons with loss of autonomy].

This article is about the relation between, on the one hand, support provided by third parties and, on the other, the burden and the depression experienced by the main female supporters who care for the elderly suffering from physical or cognitive problems. The authors examine the hypothesis that social support is not homogeneous across the board and that the different types of support are likely to have different effects on elders with adverse reactions to the caring process. Data originates from a study that was conducted in the Montréal area in 1990 with 159 female supporters living with an elder requiring care who requested support services from formal and informal networks. Hierarchical regression analyses show that the variables in connection with care dispensed by the network play a limited role in attempting to explain the depression and burden levels. Furthermore, these analyses confirm the hypothesis of the variables' narrow range of influence.


[Future perspectives, factors in the mental health of aged persons].

During individual interviews, 708 people between the ages of 65 and 90 expressed a wide variety of personal goals and aspirations through sentences they were asked to complete. The distribution of answers in temporal categories provides an index of the broadening of future perspectives (PF). The values of that index were put in relation with subjective assessments that can be looked upon as clues to mental health. Results confirm the hypothesis of a positive relation between PF and perception of health (0.27), meaning of life (0.29), living satisfaction (0.30) and perception of having personal control (0.18). However, PF does not appear to be connected with the person's attitude toward death. These results seem to indicate that PF represents a factor of mental health and "healthy aging". Consequently, they justify the relevance of developing interventions that aim to strengthen this "personal resource".


[Reactions of social workers in a mental health day center and the avoidance of institutionalization of individual defense mechanisms].

The author attempts to describe the different strengths that emerge from the role of the supervisor (clinic) in a community organization in relation to two aspects: the maintaining of the defining characteristics of the notion of "alternative" and the dynamic understanding of the social worker-user relationship. After a review of how a day centre operates, the author describes the individual and collective "defense mechanisms" that are used by social workers to alleviate the impact of the user's baffling behaviour on their personality. The author follows by showing that failure to use these defense mechanisms can lead to burnout for the social worker, while certain forms of collective defense mechanisms can prompt this alternative care system to institutionalize itself from within.


[Analysis of the medical and psychosocial evaluations required by the new public curator law].

The new Public Curator Act systematically requires medical and psychosocial evaluations. In confronting the letter and the spirit of the law to its regulations and operating procedures (and inversely), this article outlines the various tasks that will fall under the responsibility of health and social service professionals. Following a brief presentation of the law, the authors describe how the role of these professionals is limited to evaluations for the purpose of conducting expert appraisements, a matter which raises a great deal of concern. In addition, the two key notions of "inaptitude" and "need" are discussed in their legal sense, along with their consequences from the medical evaluation and psychosocial standpoints. The latter in particular will be analyzed regarding implementation difficulties. The authors conclude with a general commentary that is likely to give meaning to that simple and sometimes routine gesture consisting of "completing a form".


[Mental health of migrants: analysis of the social and longitudinal context].

The mental health of migrants is affected by many factors that stem from premigratory experiences as well as adaptation conditions of the host nation. The interaction of these two types of factors are however set in time: certain periods are characterized by relative stability, while others are marked by unexpected disruptions which tend to make migration appear as a never-ending process. An individual's age upon arrival in a new country is also an important factor: adolescents must meet many different types of demands, while the elderly no longer have the personal resources to assimilate a new culture. The author points out that adaptation takes place in a family system where the fortune of each member impacts on that of others in the family. In this article, the author discusses prevention by taking into consideration certain issues raised by scientific literature.


[Political migration, economic migration: a systemic lecture on the process of integration by migrant families].

In this paper, the author aims to establish links between the family, the socio-cultural system and migration, a process which represents a significant relocation of the space in which one or several living systems evolve. The concepts of family and migration are meshed in order to present explicative models of the operation and the adaptation guidelines of families undergoing migration. The author bases his study on his role as an observer and human being who is striving to make sense of his environment and create a dialogue around a theme that deeply disturbed him in his individual, family and social phenomenology.


[Theoretical and methodological principles of ethnopsychiatry: the example of migrant children and their families].

The realm of ethnopsychiatry also includes the cultural dimension of chaos (and the ways of overcoming this chaos) and the analysis of psychic foundations. This original method deals with the "complementarity" between psychoanalysis and anthropology. In doing so, it establishes a new link between the clinician and the patient, between traditional therapies and modern treatments, between the outside (culture) and the inside (psyche). This approach can be successfully applied to the context of migration, particularly to the child who is torn between the culture of his parents and the culture of the host nation.


[The clinician's cultural identity and its role in the relation with the patient].

From an interactionist point of view, the cultural life history of the clinician is as important as that of the patient. In present day Europe, migratory upheavals have requested adjustments at all levels. There are foreign patients, yet professionals are themselves also culturally diversified. Affected by the migration stress, they too are submitted to its effects. The author proposes that the patient/clinician relationship be revisited in the light of the interpretative-reflexive interaction model between informant and ethnographer in the anthropological fieldwork.


Quantifying the value of human life for cost accounting of safeguards: clarifying formulas applied to the clozapine controversy.

Using CPMS as an example, this article has developed mathematical formulations to compare the value of lives saved against the cost of medical safeguards. By a logical comparison of benefit and cost converted to the same units of currency, the article explores three important questions relating to the CPMS example. These mathematical formulations serve to quantify the decision-making process in a logical manner, and might serve as a useful example for clinical and public policy decisions.