Social representations of intellectual disability; a comparison between cultures.

OBJECTIVES: People with Intellectual disability consistently appear to be one of the most looked-down upon and repressed subgroups of society in many cultures. The main aim of this study was to compare social representations of intellectual disability in its various aspects between different cultures. MATERIALS AND METHODS: The study was conducted in four different sites: Beirut-Lebanon, Algiers-Algeria, Tours-France and Namur-Belgium. Participants were asked to complete a questionnaire evaluating social representations of intellectual disability. RESULTS: A total of 755 participants consented to take part in the study. Gender only affected social representations in the Lebanese population. Overall, Algerians appeared to have the least positive social representations and Lebanon to have more positive attitudes, while France and Belgium tended to have the most favourable representations. DISCUSSION AND CONCLUSIONS: Findings highlight the imbalance between a European and a non-European country showing the importance of developing tailored interventions to improve general attitudes towards intellectual disability.

Neuroprotective effects of a dendrimer-based glutamate carboxypeptidase inhibitor on superoxide dismutase transgenic mice after neonatal hypoxic-ischemic brain injury.

The result of a deprivation of oxygen and glucose to the brain, hypoxic-ischemic encephalopathy (HIE), remains the most common cause of death and disability in human neonates globally and is mediated by glutamate toxicity and inflammation. We have previously shown that the enzyme glutamate carboxypeptidase (GCPII) is overexpressed in activated microglia in the presence of inflammation in fetal/newborn rabbit brain. We assessed the therapeutic utility of a GCPII enzyme inhibitor called 2-(3-Mercaptopropyl) pentanedioic acid (2MPPA) attached to a dendrimer (D-2MPPA), in order to target activated microglia in an experimental neonatal hypoxia-ischemia (HI) model using superoxide dismutase transgenic (SOD) mice that are often more injured after hypoxia-ischemia than wildtype animals. SOD overexpressing and wild type (WT) mice underwent permanent ligation of the left common carotid artery followed by 50 min of asphyxiation (10% O2) to induce HI injury on postnatal day 9 (P9). Cy5-labeled dendrimers were administered to the mice at 6 h, 24 h or 72 h after HI and brains were evaluated by immunofluorescence analysis 24 h after the injection to visualize microglial localization and uptake over time. Expression of GCPII enzyme was analyzed in microglia 24 h after the HI injury. The expression of pro- and anti-inflammatory cytokines were analyzed 24 h and 72 h post-HI. Brain damage was analyzed histologically 7 days post-HI in the three randomly assigned groups: control (C); hypoxic-ischemic (HI); and HI mice who received a single dose of D-2MPPA 6 h post-HI (HI+D-2MPPA). First, we found that GCPII was overexpressed in activated microglia 24 h after HI in the SOD overexpressing mice. Also, there was an increase in microglial activation 24 h after HI in the ipsilateral hippocampus which was most visible in the SOD+HI group. Dendrimers were mostly taken up by microglia by 24 h post-HI; uptake was more prominent in the SOD+HI mice than in the WT+HI. The inflammatory profile showed significant increase in expression of KC/GRO following injury in SOD mice compared to WT at 24 and 72 h. A greater and significant decrease in KC/GRO was seen in the SOD mice following treatment with D-2MPPA. Seven days after HI, D-2MPPA treatment decreased brain injury in the SOD+HI group, but not in WT+HI. This reduced damage was mainly seen in hippocampus and cortex. Our data indicate that the best time point to administer D-2MPPA is 6 h post-HI in order to suppress the expression of GCPII by 24 h after the damage since dendrimer localization in microglia is seen as early as 6 h with the peak of GCPII upregulation in activated microglia seen at 24 h post-HI. Ultimately, treatment with D-2MPPA at 6 h post-HI leads to a decrease in inflammatory profiles by 24 h and reduction in brain injury in the SOD overexpressing mice.

[Sensorimotor aspects and manual dexterity in autism spectrum disorders: A literature review]. / Aspects sensorimoteurs et motricité manuelle dans les troubles du spectre autistique : une revue de la littérature.

OBJECTIVES: Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by difficulties in communication and social interactions as well as by restricted and repetitive patterns of behavior and interests. They are frequently associated with motor signs. However, literature concerning these motor anomalies remains scarce when it comes to the adult population. Among motor aspects, those concerning manual motor skills warrant a particular attention as their alteration often persists through adulthood with a major impact on functioning and quality of life. The purpose of this article was to systematically review and analyze the literature on sensorimotor aspects and manual motor impairments in ASD. METHODS: We have searched the Medline database using the Pubmed search engine and retaining all articles published since the year 2000 with either their title, abstract or key-words containing the root autis* and any combination of the following terms: hand, manual, finger, dexterity, prehension, grip or grasp. Reference lists where also reviewed. After irrelevant articles were excluded, 33 studies were retained for this work. RESULTS: The basic motor anomaly in autism seems to be a deficit in sensorimotor integration. The central nervous system of individuals with ASD seems unable to efficiently extract sensory information and integrate it correctly into a motor plan and execution. This type of online correction aims to save time on the initial ballistic phase of a movement. Thus, its alteration results in generalized slowness and motor clumsiness that require retroactive feedback corrections. Moreover, difficulties in integrating external sensory information to correctly adapt movement to environmental requirements could explain stereotyped and inflexible behaviors characteristic of autism. The same sensorimotor alterations are found in both gross and fine manual dexterity tasks. They seem to persist significantly though adolescence and into adulthood. To explain these anomalies, the underlying neuroanatomical and neurofunctional substratum might be a hypoconnectivity within cortico-cerebellar tracts. However, several other cerebral structures are also implicated. A delay in the maturational processes of these structures appears to be the common determinant of motor signs found in ASD but also in neurodevelopmental disorders as a whole. CONCLUSIONS: Current works tackling motor aspects in autism comprise several limitations preventing homogenization of their findings. Firstly, characterization of the extremely diverse clinical forms of ASD does not always rely on the same clinical criteria or tools. Furthermore, the motor tasks and the clinical assessments used are not always the same across publications complicating comparison. Moreover, sample sizes are almost always small and only a few studies have addressed motor impairments in adults with ASD. Furthermore, only two studies examine the dynamic longitudinal evolution of motor aspects from childhood to adult age. Finally, despite a recent effort of a consistent number of publications converging towards the hypothesis of a deficit in sensorimotor integration, a common pathophysiological model explaining these deficits in ASD is lacking. A more precise description of these motor signs and further comprehension of the neurological mechanisms underpinning them would allow more tailored managements directed towards subgroups with more homogenous neurodevelopmental profiles.

[Patterns of prescription of opioid analgesics in Hôtel-Dieu de France of Beyrouth]. / Les modalités de prescription d'analgésiques opiacés par les médecins de l'Hôtel-Dieu de France de Beyrouth.

OBJECTIVES: Use of chronic opioid therapy has increased substantially over the past few years, even though opioid therapy is associated with potentially serious harms, including opioid-related adverse effects and outcomes. Prescription of opioids for chronic pain, particularly nonmalignant chronic pain, remains controversial. In the midst of this controversy, patterns of actual prescription and influences on these patterns are not well understood. This study aims to describe the frequency of prescription of opioid analgesics in a university hospital, the attitudes of doctors towards this category of drugs, and the follow-up modalities of patients taking these drugs. The study also explores the association between the practitioners' characteristics and the modalities of prescription. DESIGN AND METHODS: A survey was delivered to 112 doctors and surgeons in the hospital during the four months between August and December 2013 and it was returned by 55 (49.0%). The survey consists of three parts. The first part addresses the frequency and reluctance of doctors' prescription of opioids and other analgesics for acute and chronic pain. The second part studies the doctors' attitudes and concerns towards opioids. It explores the belief of the doctors in the efficacy of this category of drugs, their confidence in prescribing such medications and the eventual side effects they might worry about. The third part of the survey studies the modalities of evaluation prior to the prescription and the modalities of follow-up of the patients receiving a long-term opioid treatment. RESULTS: Overall, 76.4% of doctors reported they sometimes, frequently, or always, prescribe opioids, which, using the Wilcoxon test, proved to be a significantly lower frequency than for prescribing of minor analgesics or nonsteroidal anti-inflammatory drugs (NSAIDS). Similarly, 60.1% reported a reluctance to prescribe opioids for chronic nonmalignant pain, which was a significantly greater reluctance than for cancer pain. The age and sex of the participants were unrelated to prescribing, but those with specialty training and use of practice guidelines were more likely to prescribe opioids and were less reluctant to do so. A majority of practitioners felt that opioids are effective for the treatment of chronic nonmalignant pain and that they have the sufficient training to prescribe them adequately; however, they still worry about the long-term prescription of opioids, particularly fearing the psychological dependence this treatment might cause. Using a series of Spearman correlation tests, we found that practitioners who thought they were adequately trained and who believed in the efficacy of long-term opioid treatment were more likely to prescribe them but that the worries about side effects decreased the frequency of prescription. A significant proportion of practitioners do not evaluate addiction risk factors of patients before prescribing opioids. The results concerning the modalities of follow-up of prescription were very heterogeneous with 87% of practitioners not explaining and 65% not screening for adverse effects. We similarly found that the frequency of follow-up and the management of patients who were exhibiting signs of dependence were very diverse. CONCLUSION: The results of this study were compatible with those of other recent studies about opioid prescription. The doctors practicing in the university hospital Hôtel-Dieu de France de Beyrouth present comparable prescription patterns, independent of their personal or professional characteristics, and they are more confident in their prescription when professionally trained for it. However, they exhibit a notable heterogeneity in their attitudes towards opioids and in their modalities of evaluating patients receiving long-term treatment. These results suggest a need for additional training in the management of this category of drugs.

Online Oncology Careers Events to Attract the Future Oncology Medical Workforce: An Exemplar Event and Review of the Literature.

AIMS: There are too few oncologists to meet the increasing burden imposed by the rising incidence of cancer. This results from issues with the retention of established oncologists and longstanding challenges to the recruitment of adequate numbers of trainees. To counter this, the British Oncology Network for Undergraduate Societies (BONUS) devised an online oncology careers event for medical students and junior doctors who are yet to select a specialty. MATERIALS AND METHODS: An online careers event was devised with a focus on oncology practice and related subspecialties, as well as research. Event attendees were asked to respond to piloted pre- and post-event surveys. Knowledge and attitudes towards a career in oncology were evaluated using Likert scale and multiple-choice questions. A systematic literature search was carried out to contextualise these data. RESULTS: Of the 73 attendees, 44 (60%) participants completed both the pre- and post-event surveys; 79.5% of attendees believed that information on a career in oncology is lacking in medical training. This viewpoint was supported by the systematic review, which highlighted a need for relevant focussed interventions targeted at medical students and fledgling doctors. The education event led to an increase in the median reported understanding of the oncology career pathway from 6.0 to 8.0 (P < 0.05 and P < 0.001), as well as the likelihood of pursuing a career in oncology (8.0-9.0; P < 0.05). It was also associated with a proportional increase in medical and surgical oncology interest, albeit with a fall in interest in clinical and interventional oncology as well as academia. CONCLUSION: A targeted online careers event increases knowledge of and interest in a career in oncology, albeit predominantly for medical and surgical subspecialties. Broader initiatives based on our model should be developed and careers in academia as well as clinical and interventional oncology emphasised.

WALANT in hand surgery: Ischemic complications and their medicolegal implications in France: A systematic review of the literature and of French legal databases.

WALANT (Wide Awake Local Anesthesia No Tourniquet) presents a theoretical risk of digital ischemia due to the presence of epinephrine, associated to the local anesthetic. For this reason, in France, the market authorization prohibits the use of epinephrine in digital extremities. The main objective of the present study was to assess the risk of ischemic complications reported in literature, and then to analyze the medicolegal implications in France. A systematic literature review was performed by three independent readers, using the PubMed and Embase databases. Also, declarations of claims and legal proceedings between 2007 and 2020 in France were examined in the official national Légifrance and Doctrine databases. Eight of the 424 articles retrieved were selected. Only 3 cases of digital necrosis following local anesthesia with adrenalized lidocaine were reported. Adrenalized xylocaine may be considered in case of peripheral microcirculation disorder. From a medicolegal point of view, no complaints or medicolegal implications were associated with WALANT in France. It seems that the market authorization for adrenalized local anesthesia could be extended to use in the digital extremities. However, the lack of medical and legal data calls for caution. We therefore recommend the use of an institutional protocol specifying the cases of overdose and the patient's pathway, and training for practitioners wishing to use this technique.

Medical Student Perspectives on Undergraduate Oncology Education in the UK.

AIMS: The British Oncology Network for Undergraduate Societies (BONUS) surveyed students who attended an oncology revision day to determine their views on the current quantity, quality and type of curriculum-based oncology teaching they have experienced. MATERIALS AND METHODS: Students attending two BONUS revision days received a questionnaire assessing their experience of oncology teaching within the medical curriculum and interest in pursuing a future career in oncology using a 10-point Likert scale. Data were collected with informed consent to be anonymised and used for research. Student demographics and qualitative and quantitative data about experiences of oncology education were analysed. RESULTS: In total, 451 students registered to attend the revision days. After removal of duplicates, non-responders and non-UK participants, responses from 153 students studying across years 1-6 at 22 UK medical schools were analysed. The mean quantity of oncology lectures students reported receiving was 8.9 hours and the mean quantity of clinic/ward-based oncology teaching was 7.5 hours. Ninety (62.1%) of the 145 students who responded to the relevant question reported that they had received dedicated teaching in oncology. Students who had received dedicated oncology teaching reported a statistically significantly higher mean quality 6.1 (95% confidence interval 5.6-6.5) versus 5.0 (95% confidence interval 4.3-5.5; P = 0.003) and quantity 5.2 (95% confidence interval 4.7-5.6) versus 4.3 (95% confidence interval 3.7-4.9; P = 0.03) of oncology teaching compared with those who had not received this. CONCLUSION: Appropriate oncology education is essential for all medical students due to the high prevalence of cancer. All future doctors need the appropriate knowledge and communication skills to care for cancer patients. Our analysis provides quantitative evidence to support the value of specialist oncology teaching within the medical school curriculum in improving student-reported experience. National student-led revision days and events may widen interest in a future career in oncology and aid collaboration between oncology societies. It is important for the general undergraduate medical curriculum to integrate specialty content. An integrated curriculum should facilitate a holistic approach that spans prevention, screening, treatment and palliation rather than being split by subspeciality.

[Cochlear implants in elderly: performance outcomes in the long term]. / L'implant cochléaire chez le sujet âgé: évolution des performances à long terme.

OBJECTIVES: To study and compare the evolving capacities of speech discrimination with cochlear implants in older patients compared to patients implanted at a younger age. METHODOLOGY: A retrospective study comparing a group of 52 patients aged over 65 with a control group of 58 patients aged between 30 and 50 years, followed for 5 years after implantation. We analyzed and compared the evolution of speech discrimination in silence (disyllabic words, sentences) and noise (sentences, S/N ratio: +10 dB) after implantation. RESULTS: In the group of elderly patients, the speech discrimination in silence remains stable over time (for disyllabic words, score at 6 months: 72.8 +/- 20.2%; score at 5 years: 73.7% +/- 19.7). Discrimination in noise tends to improve (mean score at 6 months: 70.5% +/- 21.5; score at 5 years: 76.9% +/- 16.9). The results obtained are in silence are comparable to the results of the group of patients aged between 30 and 50. In noise, their performance remains lower than the control group (mean differences between scores: -10.8; confidence interval at 95%: -17.9, -5.3). CONCLUSION: The cochlear implant is effective over the long term in elderly patients, for speech discrimination in quiet and in noise. In silence, their performance is comparable to younger patients with implants.

The thyroid "microsomal" antibody revisited. Its paradoxical binding in vivo to the apical surface of the follicular epithelium.

We have shown that thyroid monolayers derived from the glands of patients with autoimmune thyroid disease have immunoglobulin (Ig) bound to their surface. This appears to have been deposited in vivo rather than during preparation of the monolayers, a view supported by our finding of such deposits on the apical margin of follicular cells in sections cut from these glands and stained with conjugated anti-immunoglobulin. It is likely that these deposits represent specific binding of so-called "microsomal" autoantibodies to the surface of the thyroid cells in vivo since staining of partially disrupted follicles ("half-melons") with Hashimoto serum containing microsomal autoantibodies in the indirect immunofluorescence (IFL) test, localized the antigen on the apical surface of the cells lining the follicular cavity. Thus, paradoxically, although the antigen is relatively inaccessible, autoantibodies do reach and combine with the thyroid surface in vivo and may therefore play a role in pathogenesis.

Reexpression of blood group ABH antigens on the surface of human thyroid cells in culture.

Using indirect immunofluorescence (IFL) on viable human thyroid cultures, it has been shown that, although adult follicular cells do not express blood group ABH antigens in vivo, they invariably reexpress the corresponding antigens on the cell surface when cultured in monolayers, even for very short periods. The absence of blood group antigens on noncultured thyroid cells was confirmed by negative IFL on cell suspensions obtained after enzymatic digestion of the glands, whereas these antigens were readily demonstrable on cell suspensions obtained by trypsinization of established monolayers. The quantitative expression of ABH antigens on individual thyroid cells was variable and the cell-surface IFL pattern due to binding of blood group isoantibodies was different from that given by organ-specific thyroid autoantibodies on viable cultures. Reexpression of blood group antigens by cultured thyroid cells could not be related to the secretor status of the donors, the presence of a particular source of serum in the culture medium or cell division in vitro. After 2-3 wk in culture, thyroid cells became morphologically dedifferentiated and no longer displayed blood group antigens, though they still expressed cell-surface beta 2-microglobulin. Fibroblasts present in the primary thyroid cultures were invariably negative for ABH antigens. These results demonstrate that the surface antigenic repertoire of cultured human cells is not necessarily identical to that present on the same cells in vivo. Furthermore, the possibility that blood group natural isoantibodies bind to the cell surface must be taken into account in experiments in which cultured thyroid cells are exposed to human sera.

Non-Hodgkin's lymphomas with Burkitt-like cells are associated with c-Myc amplification and poor prognosis.

Out of 344 patients with newly diagnosed non-Hodgkin's lymphoma (NHL), this study identified 16 patients presenting Burkitt-like cells (BLCs) after cytological and/or histological review. Conventional cytogenetic analysis showed at diagnosis complex chromosomal abnormalities in 13 cases and a normal karyotype in three cases. However, neither t(8;14)(q24;q32) nor the variants t(2;8)(p12;q24) or t(8;22)(q24;q11) was detected. FISH studies showed c-MYC amplification in all cases with four to more than seven copies in 10 - 77% metaphase or inter-phase cells. This study did not observe any gene fusion signal for c-MYC/IgH excluding a t(8;14) translocation and partial tri or polysomy of chromosome 8. It also excluded in that cases a break apart for the c-MYC locus. This study also never detected IgL/c-MYC, IgK/c-MYC or X-c-MYC. The BLCs were present whatever the lymphoma sub-type: follicular lymphoma (FL) was diagnosed in six out of 16 patients, mantle cell lymphoma (MCL) in four out of 16 patients, marginal zone lymphoma (MZL) in two out of 16 patients and diffuse large B-cell lymphomas (DLBCL) in three out of 16 patients. One additional patient presented a T-cell lymphoma. The clinical course was aggressive with a poor prognosis, as death occurred in nine patients, within 6 months after diagnosis for eight of them. These data could suggest a sub-group of NHL patients (15 B-NHL, 1 T-NHL) have been identified with a poor prognosis characterized by the association of Burkitt-like cells and c-MYC amplification without t(8;14)(q24;q32) or its variants. The possibility that this profile may represent a distinct morphologic NHL sub-set remains to be determined on a large cohort of patients.

Effects of butyric acid on cell cycle regulation and induction of histone H1(0) in mouse cells and tissue culture. Inducibility of H1 (0)in the late S-G2 phase of the cell cycle.

We have examined the regulation of the synthesis of histone H1(0) in cultured mammalian cells treated with butyric acid. Treatment of cells with the inducer results in the arrest of synthesis of DNA and the other histones, while increasing the synthesis of H1(0) by a factor of 11. The induction of H1(0) by butyric acid occurs in a pulse with a peak at six hours, followed by a decrease to negligible levels. This pulse-like induction appears to be due to the fact that the cells are inducible for H1(0) only in the late S or G2 phases of the cell cycle. This, coupled with the fact that butyric acid blocks cells in G1, results in the burst of H1(0) synthesis after addition of the inducer. The G1 block provoked by butyric acid does not appear to result from the accumulation of H1(0). Removal of butyric acid from G1-blocked cells resulted in the resumption of cellular proliferation without prior loss of H1(0), demonstrating that the presence of this histone is not sufficient to prevent cellular proliferation.

Tumor necrosis factor alpha in human long-term bone marrow cultures: distinct effects on nonadherent and adherent progenitors.

Although tumor necrosis factor alpha (TNF alpha) exerts a variety of activities on hematopoietic cells, suggesting it may have some potential therapeutic applications, its long-term effects on hematopoiesis are not well defined. Therefore, we took the advantage of long-term bone marrow cultures (LTBMCs) to evaluate the long-term role of TNF alpha on both the microenvironment and the hematopoietic progenitors. LTBMCs were inoculated with 100 U/ml of recombinant human TNF alpha (rhTNF alpha) either at the onset of the cultures (d0) or at day 21 (d21) when the adherent layer (AL) was already established. Then TNF alpha was added at each weekly medium change. The cellularity and the content of progenitors in both the nonadherent layer (NAL) and AL, the formation of the AL, and the presence of various cytokines in the supernatants were examined weekly. The data showed 1) a strong and durable inhibitory effect on total nonadherent cells; 2) a rapid and transient inhibition of NA progenitors, whereas adherent progenitors were lately affected; and 3) microenvironmental changes consisting of the disappearance of adipocytes and the secretion of high levels of interleukin 6. The results suggest that the inhibitory effects of TNF alpha on the NAL are in part counterbalanced by stromal modifications that in turn lead to a faster exhaustion of hematopoiesis.

Reversible inhibitory effects and absence of toxicity of the tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) in human long-term bone marrow culture.

The effects of acetyl-N-Ser-Asp-Lys-Pro (Ac-SDKP) in human long-term bone marrow cultures (LTBMCs) were assessed by measuring the number of progenitors and the development of stromal cells over a 6-week course. In a first set of experiments, AcSDKP was added weekly at each medium change. Under these conditions, no significant effect of the peptide was observed. In contrast, by adding AcSDKP daily at 10(-10) M, the growth of the progenitors of the non-adherent (NA) compartment was inhibited by about 35%. This inhibition was entirely reversible; after stopping the addition of the peptide at the fourth week, the number of progenitors returned to control level within 2 weeks. Conversely, AcSDKP did not significantly change the number of the progenitors present in the adherent layer. In addition, AcSDKP did not affect the formation of the stromal layer nor induce the secretion of cytokines, such as tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), granulocyte colony-stimulating factor (G-CSF), interleukin 3 (IL-3), or interleukin 6 (IL-6). Our results indicate that AcSDKP has inhibitory but reversible effects on NA progenitors and does not induce long-term modifications of the microenvironment, both of particular interest for its clinical application.

HLA-DR expression by hair follicle keratinocytes in alopecia areata: evidence that it is secondary to the lymphoid infiltration.

There is evidence suggesting that alopecia areata (AA) may have an autoimmune pathogenesis, and it was recently reported that keratinocytes in the bulb of some hair follicles affected by this condition express class II HLA (HLA-DR) antigens, which are not present on the same cells in normal tissue. Since it has been proposed that an analogous ectopic HLA-DR expression by epithelial cells in other organs might be an early event leading to organ-specific autoimmunity, we have investigated the sequence in which perifollicular mononuclear cell (MNC) infiltration and ectopic HLA-DR expression on keratinocytes appear in recent-onset and long-standing cases of AA by immunostainings of affected and unaffected areas with monoclonal antibodies against leukocyte and HLA-DR antigens. In recent-onset AA lesions, ectopic HLA-DR expression on hair follicle keratinocytes was found only occasionally (in 3 out of 247 follicles examined) and was restricted to biopsies from the affected areas. This prevalence was significantly lower than the prevalence of hair follicles showing perifollicular MNC infiltrates in the same biopsies, and was also significantly lower than the prevalence of hair follicles showing ectopic HLA-DR expression on keratinocytes in the affected areas of longstanding cases. These findings suggest that in AA lesions the perifollicular MNC infiltration precedes the ectopic HLA-DR expression on hair follicle keratinocytes, and therefore argue against the notion of a primary role for that ectopic HLA-DR expression on epithelial cells in triggering the putative autoimmune response in AA.

Topical minoxidil in alopecia areata: no effect on the perifollicular lymphoid infiltration.

The therapeutic value of topical minoxidil in alopecia areata (AA) has been investigated in recent years, with variable results. Although the mechanism whereby minoxidil may stimulate hair regrowth in some cases of AA has not yet been elucidated, there have been reports of a decrease in the perifollicular infiltrates of mononuclear leukocytes (MNC)--particularly T lymphocytes--that characterize this condition, in patients "responding" to topical minoxidil. In a randomized and double-blind study, we have investigated the effect of 5% topical minoxidil versus placebo (vehicle alone) on the extent and composition of the perifollicular MNC infiltration in 20 patients having extensive AA (26-99% scalp hair loss). The proportions of hair follicles showing perifollicular infiltration by MNC and their main subsets were determined with histologic and immunohistochemical stainings of scalp biopsies obtained before treatment, after 12 weeks of randomized double-blind minoxidil versus placebo treatment, and after 12 additional weeks during which all patients received minoxidil. Six of the patients showed cosmetically acceptable hair regrowth (CAHR) at the end of the 24 weeks and this was associated with a significant decrease in the proportions of follicles infiltrated by total T and B lymphocytes, macrophages, and Langerhans cells at week 12, and by total T lymphocytes at week 24. However, no significant differences in the extent or composition of the perifollicular infiltrates were detected at week 12 between patients receiving minoxidil and placebo, or between the week-12 and week-24 biopsies of those patients who first received placebo and then minoxidil. These findings indicate that in AA the reduction in perifollicular T-cell infiltration associated with CAHR is not attributable to an effect of topical minoxidil.

Ectopic expression of HLA class II antigens on thyroid follicular cells: induction and transfer in vitro by autologous mononuclear leukocytes.

Ectopic expression of HLA class II antigens by thyroid follicular cells (TFC) might trigger the immune recognition of TFC-specific surface constituents by self-reactive T helper/inducer lymphocytes, with the consequent generation of organ-specific autoimmunity. To explore the alternative possibilities underlying this ectopic expression, i.e. that it either reflects a primary abnormality of the TFC or is secondarily induced by the autoimmune attack itself, we employed immunofluorescence staining of monolayers cultured from thyroid tissue of patients with autoimmune thyroid disease as well as neoplastic, nodular, and normal thyroid tissues to assess the role that autologous mononuclear leukocytes (MNC) and serum factors play in HLA class II induction and modulation in vitro. In all Graves' disease (GD) tissues that initially displayed HLA-DR (DR) antigens, this expression was transient. Primary TFC cultures from tissues with tumor-associated chronic thyroiditis (CT) showed more widespread and persistent DR expression than did cultures from GD tissues. However, in contrast with the findings in GD, there was no correlation between ectopic DR expression on TFC from the CT areas and the presence of organ-specific autoimmune markers. DR expression by TFC was detected in only one of the five nontoxic nodules studied, and involved a small proportion (approximately 20%) of the TFC. A similarly low proportion of DR-positive TFC was found in cultures from two papillary carcinomas, while much stronger DR expression was seen on TFC cultured from the contralateral lobes affected with CT. Only one of four follicular adenomas expressed DR on about 35% of the cultured TFC. In contrast with the rapid extinction of DR expression on TFC cultured from GD tissues after depletion of infiltrated MNC, DR antigen loss did not occur or was significantly delayed when parallel TFC monolayers were cocultured in the presence of autologous MNC from the intrathyroidal infiltrates. Coculture of DR-negative TFC from normal tissues with autologous peripheral blood MNC in individuals without detectable thyroid autosensitization also resulted in pronounced induction of DR expression on the TFC. Purified T lymphocytes from the same peripheral blood MNC preparations, however, did not induce DR expression on these normal TFC. Similarly, MNC obtained from two follicular adenomas, mostly macrophages, did not induce DR expression when cultured with autologous TFC from the same lesions. Addition of 15% autologous serum did not prevent progressive extinction of DR expression on TFC cultured from GD or tumor-associated CT tissues after depletion of infiltrated MNC.(ABSTRACT TRUNCATED AT 400 WORDS)