Interactions of "Limax amoebae" and gram-negative bacteria: experimental studies and review of current problems

Free-living amoebae can harbour bacteria inside their cysts giving them a microhabitat and protecting them from disinfectants. The aim of this study was to evaluate the potential importance of "Limax amoebae" as vectors for environmental and nosocomial bacteria in a hospital. It was shown that free-living amoebae are ubiquitous in the investigated hospital, occur syntopically with facultative human pathogens (Comamonas acidovorans and Pseudomonas aeruginosa) and may serve as hosts not only for these but also for bacteria isolated from clinical specimens (Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa); temperature is apparently of crucial importance for the interactions between these microorganisms. Recent studies have shown that "Limax amoebae" apart from acting as protective hosts, may also play a role for the thermotolerance, invasiveness and antibiotic-resistance of bacteria. Considering also the reduced immune-status of many patients, this "symbiosis" of free-living amoebae and bacteria might still be of underestimated hospital-hygienic importance.     

The modern age of acne therapy: a review of current treatment options

This review of current acne treatments begins with the crucial discovery in 1979 of isotretinoin treatment for nodulocystic acne. This drug s approval in 1982 revolutionized therapy, since it was the first oral acne-specific drug, and it provided prolonged remissions. In addition, it may prevent the emergence of resistant bacteria, a problem linked to the traditional use of antibiotics for acne. Patients who are not candidates for isotretinoin therapy may benefit from one of the other drugs or drug combinations reviewed, including the third-generation topical retinoids adapalene and tazarotene, retinoic acid reformulated in new vehicles, azelaic acid, and topical antibiotics. Proper selection and education of patients are essential, since serious consequences may result from poorly monitored use of antibiotics and retinoid.     

Multiple sclerosis: current and future treatment options

Multiple Sclerosis is an inflammatory and degenerative disorder involving the central nervous system. It primarily affects young adults and may result in significant long-term disability. The most common initial presentation is relapsing remitting, followed by a chronic progressive course. In a small number of patients the disease tends to be progressive from onset. Multiple sclerosis has traditionally been described as a demylinating disorder. There is now overwhelming evidence pointing to a very significant degenerative component. Current treatment options include immunomodulating and immunosuppressive agents as well as monoclonal antibodies and target the inflammatory component of the disease resulting in significant reduction in relapses, decrease in MRI lesion load and a modest effect on disability. There are several other biological agents being developed which target different aspects of the immunopathology of multiple sclerosis. This article will review the agents currently used in the treatment of MS and also discuss agents currently under development.     

Central precocious puberty: current treatment options

Central precocious puberty (CPP) is characterized by early pubertal changes, acceleration of growth velocity, and rapid bone maturation that often result in reduced adult height. An onset of pubertal signs before the age of 8 years in girls and 9 years in boys should always be evaluated. A combination of clinical signs, bone age, pelvic echography in girls, and hormonal data are required to diagnose CPP and make a judgment concerning progression and prognosis. Not all children with apparently true CPP require medical intervention. The main reasons for treatment are to prevent compromised adult height and to avoid psychosocial or behavioral problems. The need for treatment for auxologic reasons is based on estimation of predicted adult height, with the finding of a reduced height potential, which may require a follow-up. Indication for treatment on the basis of psychologic and behavioral anomalies has to be determined on an individual basis. The main short-term aims of therapy are to stop the progression of secondary sex characteristics and menses (in girls) and to treat the underlying cause, when known. Long-term goals are to increase final adult height and to promote psychosocial well-being. Once it has been decided that treatment is appropriate, it should be initiated immediately with depot gonadotropin-releasing hormone (GnRH) agonists. The effective suppression of pituitary gonadal function is achieved with these compounds in practically all CPP patients. Long-term data are now available from 2 decades of GnRH agonist treatment for patients with CPP. Treatment preserves height potential in the majority of patients (especially in younger patients) and improves the final adult height of children with rapidly progressing CPP, with a complete recovery of the hypothalamic-pituitary-gonadal axis after treatment. GnRH agonist treatment using depot preparations is useful and has a good safety profile, with minimal adverse effects and no severe long-term consequences. Although further data are need, there may be a role in the future for combining somatropin (growth hormone) and GnRH agonist treatment for some patients with significantly impaired growth velocity. The introduction of GnRH antagonists is likely to improve the treatment options for CPP.     

The management of dermatomyositis: current treatment options

Dermatomyositis is traditionally classified as one of the idiopathic inflammatory myopathies. The traditional approach to the management of patients with dermatomyositis focuses predominantly on end points related to the systemic manifestations of this disorder, especially proximal muscle weakness resulting from myositis. However, the primary and secondary skin changes that are characteristic of dermatomyositis can, in themselves, produce significant morbidity and disability. This article presents a dermatological perspective on the management of dermatomyositis. As dermatological management approaches can vary between countries, an effort has been made to present a consensus dermatological view concerning this subject. A US dermatologist is most likely to see patients having dermatomyositis skin lesions in the following four clinical settings: soon after the onset of dermatomyositis skin disease activity before the appearance of clinically-evident muscle disease (i.e., 'pre-myopathic' dermatomyositis); during the course of clinically-amyopathic dermatomyositis; during co-management of classical dermatomyositis with other physicians; and for recrudescent skin disease activity in classical dermatomyositis patients after their symptomatic muscle inflammation has been fully suppressed by systematic immunosuppressive/immunomodulatory treatment (i.e., 'postmyopathic' dermatomyositis). Both topical and systemic therapies for dermatomyositis skin lesions encountered in these various settings will be discussed. In addition to specific approaches to the treatment of dermatomyositis skin lesions, broader management issues that dermatologists must be aware of when caring for dermatomyositis patients are included in this discussion (e.g., patient education, risk of associated systemic disease, such as myositis and interstitial lung disease, risk for occult malignancy, and prognosis counselling).     

The management of dermatomyositis: current treatment options

Dermatomyositis is traditionally classified as one of the idiopathic inflammatory myopathies. The traditional approach to the management of patients with dermatomyositis focuses predominantly on end points related to the systemic manifestations of this disorder, especially proximal muscle weakness resulting from myositis. However, the primary and secondary skin changes that are characteristic of dermatomyositis can, in themselves, produce significant morbidity and disability. This article presents a dermatological perspective on the management of dermatomyositis. As dermatological management approaches can vary between countries, an effort has been made to present a consensus dermatological view concerning this subject. A US dermatologist is most likely to see patients having dermatomyositis skin lesions in the following four clinical settings: soon after the onset of dermatomyositis skin disease activity before the appearance of clinically-evident muscle disease (i.e., ‘pre-myopathic’ dermatomyositis); during the course of clinically-amyopathic dermatomyositis; during co-management of classical dermatomyositis with other physicians; and for recrudescent skin disease activity in classical dermatomyositis patients after their symptomatic muscle inflammation has been fully suppressed by systematic immunosuppressive/immunomodulatory treatment (i.e., ‘postmyopathic’ dermatomyositis). Both topical and systemic therapies for dermatomyositis skin lesions encountered in these various settings will be discussed. In addition to specific approaches to the treatment of dermatomyositis skin lesions, broader management issues that dermatologists must be aware of when caring for dermatomyositis patients are included in this discussion (e.g., patient education, risk of associated systemic disease, such as myositis and interstitial lung disease, risk for occult malignancy, and prognosis counselling).     

Chronic hepatitis B: current and future treatment options

Hepatitis B, a major viral infection that can lead to cirrhosis and hepatocellular carcinoma, is the ninth most common cause of death worldwide. Prevention of hepatitis B virus transmission is key to reducing the spread of this serious condition. Management of chronic hepatitis B requires significant knowledge of approved pharmacotherapeutic agents and their limitations. Today, agents approved by the Food and Drug Administration for this infection are interferon-alpha-2b and lamivudine. Newer agents are being developed and hold promise: adefovir, famciclovir, ganciclovir, lobucavir, entecavir, emtricitabine, L-deoxythymidine, clevudine, a therapeutic vaccine, and thymosin alpha-1. Therapeutic options for managing hepatitis infection after liver transplantation are also evolving. These include hepatitis B immunoglobulin and nucleoside analogues.     

Diabetic painful neuropathy: current and future treatment options

Diabetic painful neuropathy (DPN) is one of the most common causes of neuropathic pain. The management of DPN consists of excluding other causes of painful peripheral neuropathy, maximising diabetic control and using medications to alleviate pain. The precise relationship between glycaemic control and the development and severity of DPN remains controversial. In this context, drugs such as aldose reductase inhibitors, ACE inhibitors, lipid-lowering agents and alpha-lipoic acid (thioctic acid) may have a useful role to play. There is also evidence that a successful pancreatic transplant may improve symptoms over time, but the mainstay of management continues to be symptomatic control of pain with drugs. Evidence from placebo-controlled studies has shown that opioids, antiepileptic and antidepressant drugs together with capsaicin are effective for alleviating DPN. Tramadol and oxycodone have been shown to be effective in studies of limited duration but their adverse effects, such as constipation and physical dependency, may limit their usefulness as a first-line treatment for DPN. Of the antidepressant drugs, the tricyclic antidepressants have been shown to be effective for alleviating DPN. These medications are widely used but their anticholinergic and sedative properties may not be well tolerated by patients. There is also good evidence that the serotonin-noradrenaline reuptake inhibitor antidepressant drugs venlafaxine and duloxetine are effective for treating DPN. However, venlafaxine may cause cardiac dysrhythmias, and patients using this medication require careful cardiac monitoring. Duloxetine appears to be less cardiotoxic and is licensed in the US and EU for alleviating DPN. The gabapentinoid group of drugs, gabapentin and pregabalin, appear to be the most evidence-based of the antiepileptic drugs for treating DPN. Large placebo-controlled studies have been performed with both of these agents. For many patients, it is still unclear what advantages pregabalin has over gabapentin for DPN. Until better evidence emerges, the potential availability of less expensive generic formulations of gabapentin, together with greater experience with its use, favour gabapentin as the main antiepileptic drug for alleviating DPN. Topiramate, lamotrigine, sodium valproate and oxcarbazepine have been shown to be effective in smaller studies but do not have the same evidence base as the gabapentinoid group of drugs. Of the newer antiepileptic drugs, lacosamide appears to be the most promising for alleviating DPN. Capsaicin has the best evidence base of all the topical agents, but local anaesthetic patches may also have a useful therapeutic role. It is not possible to nominate a single drug as the first-line treatment for DPN and there is evidence that a low-dose combination of two or more drugs rather than a single agent may provide better symptomatic relief with fewer adverse effects. Further studies are necessary to clarify the best combination(s) of treatment for DPN.     

Invasive oesophageal candidiasis: current and developing treatment options

Oesophageal candidiasis is frequently one of the first signs of HIV infection, and a marker of HIV disease. Approximately 10% of patients with AIDS or other immunodeficiency, whether due to an underlying disease, chemotherapy or radiation therapy, will experience oesophageal candidiasis during their lifetime. In addition, unless the underlying immunodeficiency is corrected, approximately 60% of patients will experience a relapse within 6 months of the initial infection. The systemic azoles have gradually replaced the use of amphotericin B for oesophageal candidiasis, and are generally safely used and effective agents for this infection. A concern in some of these patients is the appearance of antifungal-refractory oesophageal candidiasis, which frequently leads to a vicious cycle of poor oral intake, weight loss, malnutrition and wasting syndrome, with occasional mortality due to malnutrition. Newer antifungals such as voriconazole and caspofungin, which are more potent in vitro and have a broader spectrum of activity, including activity against fluconazole-resistant Candida species are a welcome addition to the antifungal armamentarium that may be used in the management of refractory mucosal candidiasis.     

Juvenile idiopathic arthritis: current and future treatment options

Juvenile idiopathic arthritis is the most common rheumatic disease in children. The management of juvenile idiopathic arthritis has improved in recent decades, and morbidity due to the disease is significantly decreased. In particular, the use of more effective drugs and their combination has changed the course of the disease in many patients. The increasing knowledge of inflammation mechanisms has lead to the development of new agents that target specific cytokines interfering with the inflammatory cascade. In particular, anti-TNF agents seem effective: etanercept is the only one licensed for juvenile idiopathic arthritis, and Phase III trials on two other anti-TNF agents, infliximab and adalimumab, are ongoing. This review discusses the current practice in the medical management of juvenile idiopathic arthritis, and potential new agents are discussed.     

Juvenile idiopathic arthritis: current and future treatment options

Juvenile idiopathic arthritis is the most common rheumatic disease in children. The management of juvenile idiopathic arthritis has improved in recent decades, and morbidity due to the disease is significantly decreased. In particular, the use of more effective drugs and their combination has changed the course of the disease in many patients. The increasing knowledge of inflammation mechanisms has lead to the development of new agents that target specific cytokines interfering with the inflammatory cascade. In particular, anti-TNF agents seem effective: etanercept is the only one licensed for juvenile idiopathic arthritis, and Phase III trials on two other anti-TNF agents, infliximab and adalimumab, are ongoing. This review discusses the current practice in the medical management of juvenile idiopathic arthritis, and potential new agents are discussed.     

Metastatic colorectal cancer: current systemic treatment options

The treatment of colorectal cancer has become increasingly complex over recent years. With the emergence of new chemotherapy drugs and targeted agents, there has been great improvement in the prognosis of patients with metastatic colorectal cancer. This review summarises the evidence supporting the use of combination chemotherapy with oxaliplatin and/or irinotecan with fluorouracil (5-FU) for the treatment of colorectal cancer and outlines the pivotal trials. Phase III trials have demonstrated the superiority of combination chemotherapy over single-agent 5-FU, but the optimal sequencing and combination of treatment is yet to be determined. Oral fluoropyrimidine derivatives have been shown to be equivalent to bolus 5-FU treatment and these offer another option for the treatment of colorectal cancer, but further studies are required to evaluate their use with irinotecan and oxaliplatin. The use of newer targeted therapies, such as bevacizumab and cetuximab, alone and in combination with chemotherapy are discussed, and the most recent data supporting their use is outlined. Bevacizumab-containing regimens have been shown to be superior to those without for the first-line treatment of colorectal cancer, and cetuximab has demonstrated activity in combination with chemotherapy in both the first- and second-line setting. Other targeted agents, such as vatalanib and panitumumab, are discussed and early clinical studies with these agents show promising results.     

Acne and its treatment options: a review

Acne vulgaris is an extremely common condition affecting more than 80-90% of adolescents and young adults. It typically starts in late childhood or early teens, but onset may be delayed in some people well into their 20s and 30s. The incidence rate of acne is roughly the same in males and females but, males tend to have more serious conditions. Common therapies that are used for the treatment of acne include topical, systemic, herbal and combination therapies. This review is an attempt to trace out the causes of acne, to know its treatment options and precautions to be taken to prevent it.     

Safety of treatment options for spondyloarthritis: a narrative review

Introduction: Spondyloarthritis (SpA) are chronic inflammatory diseases with overlapping pathogenic mechanisms and clinical features. Treatment armamentarium against SpA includes non-steroidal anti-inflammatory drugs, glucocorticoids, conventional disease-modifying antirheumatic drugs (DMARDs, including sulfasalazine, methotrexate, leflunomide, cyclosporine), targeted synthetic DMARDs (apremilast) and biological DMARDs (TNF inhibitors, anti-IL 12/23 and anti-IL-17 agents).

Areas covered: A narrative review of published literature on safety profile of available SpA treatment options was performed. Readers will be provided with a comprehensive overview on frequent and rare adverse events associated with each drug listed in current SpA treatment recommendations.

Expert opinion: The overall safety profile of such molecules is good and serious adverse events are rare but need to be promptly recognized and treated. However, the monitoring of adverse events is a major challenge for clinicians because it is not adequately addressed by current treatment recommendations. A tailored treatment is crucial and rheumatologists must accurately select patients in order to identify those more susceptible to develop adverse events.     

Lipopolysaccharide as a target for the development of novel therapeutics in gram-negative bacteria

Lipopolysaccharide (LPS) constitutes the lipid portion of the outer leaflet of Gram-negative bacteria, and is essential for growth. LPS is also known to be responsible for the variety of biological effects associated with Gram-negative sepsis. In recent years, tremendous progress has been made in determining the exact chemical structure of this highly complex macromolecule, and recent advances have elucidated much of the enzymology involved in its biosynthesis. Using this knowledge, a number of inhibitors to LPS biosynthesis have been developed: some of these compounds have antibacterial properties, while others show excellent in vitro activity and are undergoing further investigation. This review summarizes the main features of LPS structure, function, and biosynthesis, highlighting the potential target reactions that have been or might be exploited for therapeutic intervention.     

Polycystic ovary syndrome in adolescents: current and future treatment options

Polycystic ovary syndrome (PCOS) is a very common disorder affecting 5-10% of women of reproductive age. The pivotal endocrine abnormalities of this syndrome are insulin resistance and ovarian and, to a lesser degree, adrenal hypersensitivity to hormonal stimulation. PCOS may manifest itself as early as the first decade of life by premature pubarche or menarche. Oligoamenorrhea in the first postpubarchal years, although very common, may be an early symptom of PCOS, especially in overweight girls with hirsutism or acne. Girls with low birth weight as well as a family history of diabetes mellitus or premature cardiovascular disease are at high risk for developing PCOS. Circulating bioavailable testosterone levels are usually elevated, while total testosterone may be normal due to low levels of sex hormone-binding globulin. The typical sonographic appearance of PCOS ovaries consists of high ovarian volume (>10 mL) and the presence of 12 or more follicles in each ovary measuring 2-9 mm in diameter. However, this finding is not specific, since it may occur in >20% of healthy girls. The therapeutic goals in adolescents with PCOS is first to restore bodyweight and menses and to reduce the signs of hyperandrogenism. The reduction of bodyweight in this young age group may require the collaboration of the pediatrician, dietitian, and psychotherapist. The adolescent should be urged to adopt a healthy lifestyle with the aim to maintain a normal body mass index throughout adolescence and adult life. The choice of medical therapy depends on the clinical presentation. Oral contraceptives are a good option when acne and hirsutism are the principal complaints. Adolescents with isolated cycle irregularity may be placed on a cyclical progestin regimen to induce withdrawal bleeding. Metformin, by decreasing insulin resistance, alleviates many of the hormonal disturbances and restores menses in a considerable proportion of patients. It may be used alone or in combination with oral contraceptives. Independently of medical treatment, restoration and maintenance of bodyweight within normal range is of paramount importance.     

Antimuscarinics for the treatment of overactive bladder: current options and emerging therapies

Antimuscarinic drugs have been the mainstay in the treatment of overactive bladder (OAB) for over two decades. An ideal antimuscarinic medicine is one that can normalize bladder function without interfering with parasympathetic regulation of other organs. Currently, extended-release formulations of tolterodine (tolterodine-ER) and oxybutynin (oxybutynin-ER and oxybutynin-TDS) serve as the cornerstone in the pharmacotherapy of OAB. Although these products represent a significant improvement over older agents, especially with respect to convenience of dosing schedule, their tolerability concerns and modest efficacy make them less than ideal therapies. Advances in our understanding of muscarinic receptor pharmacology have raised optimism in our ability to widen the therapeutic index and increase the efficacy of antimuscarinics by selectively targeting one or more of the five muscarinic subtypes. A structurally diverse group of molecules, having varying receptor-selectivity profiles (non-selective, M3 selective, M2 selective, M2 sparing and M5 sparing), are in development for OAB. Results of clinical trials with these drugs must be awaited before their therapeutic value can be accurately judged.     

Hypopigmentary skin disorders: current treatment options and future directions

Alterations of skin and hair pigmentation are important features that have warranted treatment from ancient history on up to modern time. In some cultures, even today patients with vitiligo are regarded as social outcasts and are affected considerably both emotionally and physically. This article presents current options and future directions for the treatment of hypopigmentary disorders. Whereas with congenital disorders, such as albinism and phenylketonuria, no causal therapy has been established up to now, several treatment options for acquired hypopigmentary disorders have been investigated. In particular, in vitiligo, one of the most prevalent hypopigmentary disorders, a number of treatment modalities have been employed in the past 30 years. However, most of them are only able to palliate, not cure, the disease. Depending on the distribution of the hypopigmented lesions (localised or generalised) and the state of the disease (active or stable), several therapeutic options, for example phototherapy, surgical skin grafts, autologous melanocyte transplantation and immunomodulators, can be applied alone or in combination. For phototherapy, because of unfavourable results and adverse effects, ultraviolet (UV) A has been largely replaced by narrow-band UVB for repigmentation of generalised vitiligo. Although immunomodulators, such as corticosteroids, have been used both topically and systemically over the past 3 decades for the treatment of disseminated vitiligo, they are only suitable for the treatment of acrofacial and localised forms because of adverse effects. Hence, new immunomodulatory agents, such as calcineurin antagonists, have recently been introduced as new promising tools to treat acquired hypopigmentary disorders. However, all therapeutic approaches are hampered by the fact that the pathophysiology of hypopigmentary disorders is still poorly understood.