Premature epiphyseal closure in an adolescent treated by retinoids for acne: an unusual cause of anterior knee pain.

Retinoids are effective and widely prescribed in the treatment of severe acne. However their use can be associated with numerous side effects. Some rare cases of premature epiphyseal closure were reported. We present the case of a sixteen-year-old soccer player referred for progressive anterior pain in both knees, evoking a patellar problem. Careful pharmacological questioning revealed use of isotretinoin for several months. MRI findings showed an irregularity of the growth plate and an important metaphyso-epiphyseal oedema, more noticeable in the left knee. Retinoid-induced premature epiphyseal closure was diagnosed. The treatment was stopped, with a resolution of pain within two months. After recovery a persisting small sequelar thumbprint-like growth plate lesion was observed on the control MRI. Retinoids induce an invasion of the growth plate by osteoclasts and a decrease in proteoglycans synthesis. It seems that the knee is the most affected joint. This complication being rare, a radiological follow-up of the young patients treated by retinoids is not proposed.

Psycho-oncological interventions and psychotherapy in the oncology setting.

A person who faces the diagnosis of cancer is subjected to changes within his body, but also with regard to his view of himself and his social relationships. Cancer-related psychological distress occurs frequently and has been reported to have different prevalence according to cancer type and stage of disease. Psychological disorders are known to be underdiagnosed and thus undertreated in the oncology setting, since clinicians might miss the symptoms of psychological distress, misinterpret them, or lack the time and resources to respond adequately. The main psychiatric disturbances observed in patients with cancer are adjustment disorders and affective disorders (anxiety and depression), which in the majority of patients are due to stressors related to the disease and pre-existing psychological vulnerabilities; however, they might also be a direct consequence of biological causes either resulting from treatment side effects or from modifications induced by the cancer. This chapter aims to provide theoretical and practical information concerning psycho-oncological approaches, complemented by some reflexions on their clinical and scientific evidence, focussing essentially on verbal psychological interventions and especially on psychotherapy in patients with cancer.

Traitement non chirurgical des rectites postactiniques ou radiques chroniques [Non-surgical treatment of acute and late radiation proctitis]

Pelvic external radiotherapy with or without brachytherapy plays an important role in the management of pelvic cancers. Despite recent technical innovations including conformal three-dimensional (3D) external beam radiotherapy and more recently intensity modulated radiotherapy (IMRT), local side effects can occur secondary to normal tissue damage caused by ionising radiation. Morbidity depends on the anatomic position of the rectum within the pelvis and the fast turnover rate of the mucosa, as well as the characteristics of the radiation treatment and patient co-morbidities. Medical management is sometimes complex and merits herein a short review.

In vitro activity of Etanidazole against the protozoan parasite Trypanosoma cruzi

We investigated the in vitro action of an hydrosoluble 2-nitroimidazole, Etanidazole (EZL), against Trypanosoma cruzi, the etiologic agent of Chagas disease. EZL displayed lethal activity against isolated trypomastigotes as well as amastigotes of T. cruzi (RA strain) growing in Vero cells or J774 macrophages, without affecting host cell viability. Although not completely equivalent to Benznidazole (BZL), the reference drug for Chagas chemotherapy, EZL takes advantage in exertingits anti-T. cruzi activity for longer periods without serious toxic side effects, as those recorded in BZL-treated patients. Our present results encourage further experiments to study in depth the trypanocidal properties of this drug already licensed for use in human cancers.

Exercise aggravates cardiovascular risks and mortality in rats with disrupted nitric oxide pathway and treated with recombinant human erythropoietin.

Chronic administration of recombinant human erythropoietin (rHuEPO) can generate serious cardiovascular side effects such as arterial hypertension (HTA) in clinical and sport fields. It is hypothesized that nitric oxide (NO) can protect from noxious cardiovascular effects induced by chronic administration of rHuEPO. On this base, we studied the cardiovascular effects of chronic administration of rHuEPO in exercise-trained rats treated with an inhibitor of NO synthesis (L-NAME). Rats were treated or not with rHuEPO and/or L-NAME during 6 weeks. During the same period, rats were subjected to treadmill exercise. The blood pressure was measured weekly. Endothelial function of isolated aorta and small mesenteric arteries were studied and the morphology of the latter was investigated. L-NAME induced hypertension (197 ± 6 mmHg, at the end of the protocol). Exercise prevented the rise in blood pressure induced by L-NAME (170 ± 5 mmHg). However, exercise-trained rats treated with both rHuEPO and L-NAME developed severe hypertension (228 ± 9 mmHg). Furthermore, in these exercise-trained rats treated with rHuEPO/L-NAME, the acetylcholine-induced relaxation was markedly impaired in isolated aorta (60% of maximal relaxation) and small mesenteric arteries (53%). L-NAME hypertension induced an internal remodeling of small mesenteric arteries that was not modified by exercise, rHuEPO or both. Vascular ET-1 production was not increased in rHuEPO/L-NAME/training hypertensive rats. Furthermore, we observed that rHuEPO/L-NAME/training hypertensive rats died during the exercise or the recovery period (mortality 51%). Our findings suggest that the use of rHuEPO in sport, in order to improve physical performance, represents a high and fatal risk factor, especially with pre-existing cardiovascular risk.

Beyond the usual suspects: positive attitudes towards positive symptoms is associated with medication noncompliance in psychosis.

Antipsychotic medication represents the treatment of choice in psychosis according to clinical guidelines. Nevertheless, studies show that half to almost three-quarter of all patients discontinue medication with antipsychotics after some time, a fact which is traditionally ascribed to side-effects, mistrust against the clinician and poor illness insight. The present study investigated whether positive attitudes toward psychotic symptoms (ie, gain from illness) represent a further factor for medication noncompliance. An anonymous online survey was set up in order to prevent conservative response biases that likely emerge in a clinical setting. Following an iterative selection process, data from a total of 113 patients with a likely diagnosis of schizophrenia and a history of antipsychotic treatment were retained for the final analyses (80%). While side-effect profile and mistrust emerged as the most frequent reasons for drug discontinuation, 28% of the sample reported gain from illness (eg, missing voices, feeling of power) as a motive for noncompliance. At least every fourth patient reported the following reasons: stigma (31%), mistrust against the physician/therapist (31%), and rejection of medication in general (28%). Approximately every fifth patient had discontinued antipsychotic treatment because of forgetfulness. On average, patients provided 4 different explanations for noncompliance. Ambivalence toward symptoms and treatment should thoroughly be considered when planning treatment in psychosis. While antipsychotic medication represents the evidence-based cornerstone of the current treatment in schizophrenia, further research is needed on nonpharmacological interventions for noncompliant patients who are willing to undergo intervention but refuse pharmacotherapy.

Cognitive behavioural therapy leaflet.

This leaflet is for anyone who wants to know more about Cognitive Behavioural Therapy (CBT).It discusses how it works, why it is used, its effects, its side-effects, and alternative treatments. If you can't find what you want here, there are sources of further information at the end of this leaflet. What is CBT? It is a way of talking about: ï,§ how you think about yourself, the world and other people ï,§ how what you do affects your thoughts and feelings. CBT can help you to change how you think ('Cognitive') and what you do ('Behaviour'). These changes can help you to feel better. Unlike some of the other talking treatments, it focuses on the 'here and now' problems and difficulties. Instead of focusing on the causes of your distress or symptoms in the past, it looks for ways to improve your state of mind now. When does CBT help? CBT has been shown to help with many different types of problems. These include: anxiety, depression, panic, phobias (including agoraphobia and social phobia), stress, bulimia, obsessive compulsive disorder, post-traumatic stress disorder, bipolar disorder and psychosis. CBT may also help if you have difficulties with anger, a low opinion of yourself or physical health problems, like pain or fatigue. How does it work? CBT can help you to make sense of overwhelming problems by breaking them down into smaller parts. This makes it easier to see how they are connected and how they affect you. These parts are: ï,§ A Situation - a problem, event or difficult situation. From this can follow: ï,§ Thoughts ï,§ Emotions ï,§ Physical feelings ï,§ Actions Each of these areas can affect the others. How you think about a problem can affect how you feel physically and emotionally. All these areas of life can connect like this: {5 Areas - click related link below} What happens in one of these areas can affect all the others. There are helpful and unhelpful ways of reacting to most situations, depending on how you think about it. The way you think can be helpful - or unhelpful. An example: If you go home feeling depressed, you'll probably brood on what has happened and feel worse. If you get in touch with the other person, there's a good chance you'll feel better about yourself. If you avoid the other person, you won't be able to correct any misunderstandings about what they think of you - and you will probably feel worse. This 'vicious circle' can make you feel worse. It can even create new situations that make you feel worse. You can start to believe quite unrealistic (and unpleasant) things about yourself. This happens because, when we are distressed, we are more likely to jump to conclusions and to interpret things in extreme and unhelpful ways. CBT can help you to break this vicious circle of altered thinking, feelings and behaviour. When you see the parts of the sequence clearly, you can change them - and so change the way you feel. CBT aims to get you to a point where you can 'do it yourself', and work out your own ways of tackling these problems. [For full factsheet â?" click on link above]This resource was contributed by the National Documentation Centre on Drug Use.

Mental health and growing up factsheet. Drugs and alcohol - what parents need to know.

Information about drugs and alcohol - what parents need to know: information for parents, carers and anyone who works with young people. About this leaflet This is one in a series of leaflets for parents, teachers and young people entitled Mental Health and Growing Up. These leaflets aim to provide practical, up-to-date information about mental health problems (emotional, behavioural and psychiatric disorders) that can affect children and young people. This leaflet offers practical advice for parents, teachers and carers who are worried that a young person is misusing drugs or alcohol. Why do I need to know about a young person using drugs or alcohol? Many young people smoke, drink alcohol and may try drugs. It is important you are aware of this and do not ignore it as a time when they are just having fun or experimenting. It doesnââ,‰"¢t take much for the young people to soon lose control and to need help to recover from this problem. How common is it? By the age of 16, up to half of young people have tried an illegal drug. Young people are trying drugs earlier and more are drinking alcohol. What are the different types of drugs which cause problems? The most commonly used, readily available and strongly addictive drugs are tobacco and alcohol. There are numerous others that can be addictive. Alcohol and cannabis are sometimes seen as ââ,¬Ëogatewayââ,‰"¢ drugs that lead to the world of other drugs like cocaine and heroin. Drugs are also classed as ââ,¬Ëolegalââ,‰"¢ andââ,¬Ëoillegalââ,‰"¢. The obviously illegal drugs include cannabis (hash), speed (amphetamines), ecstasy (E), cocaine and heroin. Using ââ,¬Ëolegalââ,‰"¢ drugs (like cigarettes, alcohol, petrol, glue) does not mean they are safe or allowed to be misused. It just means they may be bought or sold for specific purposes and are limited to use by specific age groups. There are clear laws regarding alcohol and young people. For more detailed information on various drugs, their side-effects and the law, see ââ,¬ËoFurther Informationââ,‰"¢ at the end of the factsheet. Why do young people use drugs or alcohol? Young people may try or use drugs or alcohol for various reasons. They may do it for fun, because they are curious, or to be like their friends. Some are experimenting with the feeling of intoxication. Sometimes they use it to cope with difficult situations or feelings of worry and low mood. A young person is more likely to try or use drugs or alcohol if they hang out or stay with friends or family who use them. What can be the problems related to using drugs or alcohol? Drugs and alcohol can have different effects on different people. In young people especially the effects can be unpredictable and potentially dangerous. Even medications for sleep or painkillers can be addictive and harmful if not used the way they are prescribed by a doctor. Drugs and alcohol can damage health. Sharing needles or equipment can cause serious infections, such as HIV and hepatitis. Accidents, arguments and fights are more likely after drinking and drug use. Young people are more likely to engage in unprotected sex when using drugs. Using drugs can lead to serious mental illnesses, such as psychosis and depression. When does it become addiction or problem? It is very difficult to know when exactly using drugs or alcohol is more than just ââ,¬Ëocasualââ,‰"¢. Addiction becomes more obvious when the young person spends most of their time thinking about, looking for or using drugs. Drugs or alcohol then become the focus of the young personââ,‰"¢s life. They ignore their usual work, such as not doing their schoolwork, or stop doing their usual hobbies/sports such as dancing or football. How do I know if there is a problem or addiction? Occasional use can be very difficult to detect. If the young person is using on a regular basis, their behaviour often changes. Look for signs such as: ïâ?s§ unexplained moodiness ïâ?s§ behaviour that is ââ,¬Ëoout of character' ïâ?s§ loss of interest in school or friends ïâ?s§ unexplained loss of clothes or money ïâ?s§ unusual smells and items like silver foil, needle covers. Remember, the above changes can also mean other problems, such as depression, rather than using drugs. What do I do if I am worried? If you suspect young person is using drugs, remember some general rules. ïâ?s§ Pay attention to what the child is doing, including schoolwork, friends and leisure time. ïâ?s§ Learn about the effects of alcohol and drugs (see websites listed below). ïâ?s§ Listen to what the child says about alcohol and drugs, and talk about it with them. ïâ?s§ Encourage the young person to be informed and responsible about drugs and alcohol. ïâ?s§ Talk to other parents, friends or teachers about drugs - the facts and your fears and seek help. If someone in the family or close friend is using drugs or alcohol, it is important that they seek help too. It may be hard to expect the young person to give up, especially if a parent or carer is using it too. My child is abusing drugs. What do I do? ïâ?s§ If your child is using drugs or alcohol, seek help. ïâ?s§ Do stay calm and make sure of facts. ïâ?s§ Don't give up on them, get into long debates or arguments when they are drunk, stoned or high. ïâ?s§ Donââ,‰"¢t be angry or blame themââ,‰?othey need your help and trust to make journey of recovery. Where can I get help? You can talk in confidence to a professional like your GP or practice nurse, a local drug project or your local child and adolescent mental health. They can refer your child to relevant services and they will be able to offer you advice and support. You may also be able to seek help through a school nurse, teacher or social worker. You can find this information from your local area telephone book or council website, or ask for the address from your health centre. [For the full factsheet, click on the link above]This resource was contributed by The National Documentation Centre on Drug Use.

Antifungal activity from Ocimum gratissimum L. towards Cryptococcus neoformans

Cryptococcal infection had an increased incidence in last years due to the explosion of acquired immune deficiency syndrome epidemic and by using new and effective immunosuppressive agents. The currently antifungal therapies used such as amphotericin B, fluconazole, and itraconazole have certain limitations due to side effects and emergence of resistant strains. So, a permanent search to find new drugs for cryptococcosis treatment is essential. Ocimum gratissimum, plant known as alfavaca (Labiatae family), has been reported earlier with in vitro activity against some bacteria and dermatophytes. In our work, we study the in vitro activity of the ethanolic crude extract, ethyl acetate, hexane, and chloroformic fractions, essential oil, and eugenol of O. gratissimum using an agar dilution susceptibility method towards 25 isolates of Cryptococcus neoformans. All the extracts of O. gratissimum studied showed activity in vitro towards C. neoformans. Based on the minimal inhibitory concentration values the most significant results were obtained with chloroformic fraction and eugenol. It was observed that chloroformic fraction inhibited 23 isolates (92%) of C. neoformans at a concentration of 62.5 µg/ml and eugenol inhibited 4 isolates (16%) at a concentration of 0.9 µg/ml. This screening may be the basis for the study of O. gratissimum as a possible antifungal agent.

Asthme a début tardif [Late-onset asthma].

Late-onset asthma is a common disease, with characteristics that differentiate it from childhood asthma persisting in adults, including a heterogeneity of underlying mechanism, a correlation with occupational exposure and the tendency to chronicize. Inadequate perception of the disease importance and difficulties in diagnosis, due to the association to COPD, the broad differential diagnosis spectrum and an atypical clinical manifestation, make this disease entity underdiagnosed and under-treated, with consequences for morbidity and mortality. The treatment of adults with asthma follows the usual guidelines, but must take into account an occasional poor therapeutic response and the risk of side effects in polymorbid patients.

Benznidazole vs benznidazole in multilamellar liposomes: how different they interact with blood components?

In spite of its widespread use, benznidazole's (BNZ) toxicity and low efficacy remains as major drawbacks that impair successful treatments against Chagas disease. Previously, attempting to increase the selectivity and reduce its toxicity on infected tissues, multilamellar liposomes (MLV) composed of hydrogenated soybean phosphatidylcholine (HSPC): distearoyl-phosphatidylglycerol (DSPG): cholesterol (CHOL) 2:1:2 mol:mol loaded with BNZ (MLV-BNZ) were designed. In this work we compared different properties of MLV-BNZ with those of BNZ. Opposite to other hydrophobic drugs, the results indicated that slight changes of BNZ×s association degree to proteins and lipoproteins should not modify the percentage of unbound drug available to exert pharmacological action. On the other hand, when loaded in MLV, BNZ reduced its association to plasma proteins in 45% and became refractory to the sinking effect of blood, dropping 4.5 folds. Additionally, when loaded in MLV, BNZ had higher volume distribution (160 ± 20 vs 102 ± 15 ml/kg) and total clearance (35.23 ± 2.3 vs 21.9 ± 1.4 ml/h.kg), and lower concentration-time curve (7.23 ± 0.2 vs 9.16 ± 0.5 µg.h/ml) than BNZ. Hence, these studies showed that for MLV-BNZ, the amount of BNZ can be substantially increased, from 25 to 70%, being this formulation more rapidly cleared from circulation than free drug; also due to the lower interaction with blood components, lower side effects can be expected.

Therapeutic failure of praziquantel in the treatment of Schistosoma haematobium infection in Brazilians returning from Africa

Several cases of therapeutic failure of praziquantel used for the treatment of urinary schistosomiasis have been reported. Alternative drugs, like niridazol and metrifonate, have shown a lower therapeutic effect and more side effects than praziquantel. Twenty-six Brazilian military men (median age of 29 years) with a positive urine parasitological exam who were part of a United Nation peace mission in Mozambique in 1994 were treated with 40 mg/kg body weight praziquantel, single dose. They swimmed in Licungo river (Mocuba city, Mozambique) during the weekends. After this, they presented haematuria, dysuria, polakiuria, and lumbar pain. Control cystoscopy examinations carried out between 6 and 24 months after each treatment (including two additional treatments at a minimum interval of 6 months) revealed the presence of viable eggs. Granulomas in the vesical submucosa were observed in 46.2% (12/26) of the individuals. A vesical biopsy confirmed the presence of granulomas in all of these patients and the presence of viable eggs in 34.3% (9/26) of individuals who no longer excreted eggs in urine. The eggs filled with miracidia showed characteristics of viability. Histopathological examination using different strains demonstrated therapeutic failure and the need for repeated treatment. In this study, we demonstrated a low efficacy of praziquantel in the treatment of schistosomiasis haematobia, and the necessity of the urinary bladder biopsy as criterion of cure.

Melan-A-specific cytotoxic T cells are associated with tumor regression and autoimmunity following treatment with anti-CTLA-4.

PURPOSE: Ipilimumab is a monoclonal antibody that blocks the immune-inhibitory interaction between CTL antigen 4 (CTLA-4) and its ligands on T cells. Clinical trials in cancer patients with ipilimumab have shown promising antitumor activity, particularly in patients with advanced melanoma. Often, tumor regressions in these patients are correlated with immune-related side effects such as dermatitis, enterocolitis, and hypophysitis. Although these reactions are believed to be immune-mediated, the antigenic targets for the cellular or humoral immune response are not known. EXPERIMENTAL DESIGN: We enrolled patients with advanced melanoma in a phase II study with ipilimumab. One of these patients experienced a complete remission of his tumor. The specificity and functional properties of CD8-positive T cells in his peripheral blood, in regressing tumor tissue, and at the site of an immune-mediated skin rash were investigated. RESULTS: Regressing tumor tissue was infiltrated with CD8-positive T cells, a high proportion of which were specific for Melan-A. The skin rash was similarly infiltrated with Melan-A-specific CD8-positive T cells, and a dramatic (>30-fold) increase in Melan-A-specific CD8-positive T cells was apparent in peripheral blood. These cells had an effector phenotype and lysed Melan-A-expressing tumor cells. CONCLUSIONS: Our results show that Melan-A may be a major target for both the autoimmune and antitumor reactions in patients treated with anti-CTLA-4, and describe for the first time the antigen specificity of CD8-positive T cells that mediate tumor rejection in a patient undergoing treatment with an anti-CTLA-4 antibody. These findings may allow a better integration of ipilimumab into other forms of immunotherapy.

BCG Moreau Rio de Janeiro: an oral vaccine against tuberculosis - review

The vaccine Bacillus of Calmette Guérin (BCG) was originally developed in France as an oral vaccine against tuberculosis. The oral use of this vaccine was replaced by the parenteral route in almost all countries after the Lubeck disaster. In contrast, Brazil retained the oral delivery of the vaccine until the mid-seventies when it was replaced by the intradermal route. This change in route of delivery was mainly secondary to pressure by medical practitioners based on the poor responses of oral immunized subjects to purified protein derivative (PPD) skin tests. Even after the change of route of delivery, Ataulpho de Paiva Foundation continued making the oral vaccine. Currently, BCG Moreau has been described as one of the most immunogenic and with fewer side effects than other BCGs. The genomics, proteomics and vaccine trials for oral BCG Moreau Rio de Janeiro are currently under investigation. In this review, we intend to describe the history of BCG Moreau Rio de Janeiro in Brazil.

Radiosensibilité individuelle : les tests vont changer nos pratiques [Intrinsic radiosensitivity: predictive assays that will change the daily practice].

The impact of curative radiotherapy depends mainly on the total dose delivered homogenously in the targeted volume. Nevertheless, the dose delivered to the surrounding healthy tissues may reduce the therapeutic ratio of many radiation treatments. In a same population treated in one center with the same technique, it appears that individual radiosensitivity clearly exists, namely in terms of late side effects that are in principle non-reversible. This review details the different radiobiological approaches that have been developed to better understand the mechanisms of radiation-induced late effects. We also present the possibilities of clinical use of predictive assays in the close future.