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1.  Advances in lens implant technology 
Cataract surgery is one of the oldest and the most frequent outpatient clinic operations in medicine performed worldwide. The clouded human crystalline lens is replaced by an artificial intraocular lens implanted into the capsular bag. During the last six decades, cataract surgery has undergone rapid development from a traumatic, manual surgical procedure with implantation of a simple lens to a minimally invasive intervention increasingly assisted by high technology and a broad variety of implants customized for each patient’s individual requirements. This review discusses the major advances in this field and focuses on the main challenge remaining – the treatment of presbyopia. The demand for correction of presbyopia is increasing, reflecting the global growth of the ageing population. Pearls and pitfalls of currently applied methods to correct presbyopia and different approaches under investigation, both in lens implant technology and in surgical technology, are discussed.
PMCID: PMC3564471  PMID: 23413369
2.  Polyclonal free light chains: a biomarker of inflammatory disease or treatment target? 
Free light chains are proteins produced by B lymphocytes during the process of antibody synthesis. Their production, as a reflection of B cell activation, can give insight into the activity of the adaptive immune system. In recent years, an automated immunoassay that provides quantitative measurement of free light chains in the serum has been developed. This assay has not only revolutionised the investigation of monoclonal light chain overproduction in plasma cell diseases, but has also allowed for the quantification of polyclonal free light chains in serum. The discovery of high levels of polyclonal free light chains in a number of inflammatory and auto-immune conditions has led to the examination of their value as a biomarker of disease activity. Research into their bio-activity has also highlighted their potential role in the pathogenesis of inflammatory disease, making them an attractive target for novel therapies.
PMCID: PMC3564472  PMID: 23413370
3.  Stronger evidence is needed before accepting that cannabis plays an important role in the aetiology of schizophrenia in the population 
Schizophrenia is a debilitating but poorly understood condition with very few known modifiable risk factors. Cannabis use can acutely induce psychotic experiences, but its causal relationship to schizophrenia is less well understood. Longitudinal cohort studies suggest that the association between cannabis and psychotic outcomes is not due to chance or reverse causation. However, the association could be due to bias or residual confounding. Methods that can test alternative explanations in greater depth are required. This is especially important as ecological studies have found little association between the increase in cannabis use over recent decades and incidence of psychotic disorders; public health models suggest that cannabis use may need to be treated and prevented in many thousands of users in order to prevent one case of schizophrenia. We believe that, while such uncertainty exists, there is a scientific duty to continue to investigate the role of cannabis in the aetiology of schizophrenia and that the policy case for considering cannabis exposure as a critical target for preventing schizophrenia is yet to be made. However, due to other evidence of the harms of cannabis use, this should not affect the public health message that cannabis can be harmful and that cannabis dependence should be prevented.
PMCID: PMC3544397  PMID: 23361397
4.  Cannabis and psychosis: what causes what? 
Converging lines of evidence suggest that cannabinoids can produce a full range of transient schizophrenia-like positive, negative and cognitive symptoms. Cannabinoids also produce some psychophysiological deficits also known to be present in schizophrenia. It is also clear that, in individuals with an established psychotic disorder, cannabinoids can exacerbate symptoms, trigger relapse, and have negative consequences on the course of the illness. Increasing evidence suggests that early and heavy cannabis exposure may increase the risk of developing a psychotic disorder such as schizophrenia. The relationship between cannabis exposure and schizophrenia fulfills some, but not all, of the usual criteria for causality. However, most people who use cannabis do not develop schizophrenia, and many people diagnosed with schizophrenia have never used cannabis. Therefore, it is likely that cannabis exposure is a “component cause” that interacts with other factors to “cause” schizophrenia or other psychotic disorders, but is neither necessary nor sufficient to do so alone. Further work is necessary to identify the factors that underlie individual vulnerability to cannabinoid-related psychosis and to elucidate the biological mechanisms underlying this risk.
PMCID: PMC3544398  PMID: 23361396
5.  Prevention of atopic dermatitis 
Atopic dermatitis now affects one in five children, and may progress to asthma and hay fever. In the absence of effective treatments that influence disease progression, prevention is a highly desirable goal. The evidence for most existing disease prevention strategies, such as avoidance of allergens and dietary interventions, has been unconvincing and inconsistent. Fresh approaches to prevention include trying to induce tolerance to allergens in early life, and enhancing the defective skin barrier to reduce skin inflammation, sensitisation and subsequent allergic disease. Early and aggressive treatment of atopic dermatitis represents another possible secondary prevention strategy that could interrupt the development of autoimmunity, which may account for atopic dermatitis persistence. Large scale and long term randomized controlled trials are needed to demonstrate that these ideas result in clinical benefit.
PMCID: PMC3515944  PMID: 23236339
6.  Lung inflammation in COPD: why does it matter? 
COPD is characterized by lung inflammation, which intensifies with disease progression. Recent studies suggest that COPD has multiple phenotypes, each with a distinct molecular pathway. Proteolytic enzymes may have a prominent role in the emphysematous phenotype, while nitric oxide pathways may be more relevant for pulmonary vessel remodelling in COPD. This article provides a synopsis of the possible role that lung inflammation plays in the pathogenesis of COPD.
PMCID: PMC3516832  PMID: 23236338
7.  Vaginal mesh – the controversy 
Pelvic organ prolapse is a condition that can cause significant symptoms that affect a woman's quality of life. It is the result of defects in the supporting structures of the vagina and, depending on the location and size, can alter the functions of the organs contained within the female pelvis. Approximately 11% of women will undergo surgical intervention for their prolapse or for incontinence in their lifetime. Unfortunately, one third of these will require reoperation for failed procedures. Pelvic floor surgeons have sought to improve these outcomes. Based largely on the success of midurethral slings (MUS), transvaginal mesh has been implanted, and commercial kits developed with the intent of improving these outcomes. In 2008, the Food and Drug Administration (FDA) issued a Public Health Notification in response to possible increased adverse events associated with the use of mesh compared to traditional repairs. The 2011 update required that further study be conducted for the use of transvaginal mesh. In this article, we wish to discuss the background of mesh use and the evolution of the public health warnings, and focus on future prospects.
PMCID: PMC3506218  PMID: 23189090
8.  Neuromodulation for treatment-resistant depression 
Treatment-resistant depression affects at least 1-3% of the US population. This article reviews the current state of focal neuromodulation therapies for treatment-resistant depression, focusing on those treatments published clinical data. These include transcranial magnetic stimulation, transcranial direct current stimulation, magnetic seizure therapy, vagus nerve stimulation, direct cortical stimulation, and deep brain stimulation among others. Of these, only two (transcranial magnetic stimulation and vagus nerve stimulation) currently have US Food and Drug Administration approval for the treatment of depression.
PMCID: PMC3506219  PMID: 23189091
10.  Quick fix or long-term cure? Pros and cons of bariatric surgery 
The past decade has seen an enormous increase in the number of bariatric, or weight loss, operations performed. This trend is likely to continue, mirroring the epidemic of obesity around the world and its rising prevalence among children. Bariatric surgery is considered by many to be the most effective treatment for obesity in terms of maintenance of long-term weight loss and improvement in obesity-related comorbid conditions. Although overly simplified, the primary mechanisms of the surgical interventions currently utilized to treat obesity are the creation of a restrictive or malabsorptive bowel anatomy. Operations based on these mechanisms include the laparoscopic adjustable gastric band and laparoscopic vertical sleeve gastrectomy (considered primarily restrictive operations), the laparoscopic biliopancreatic diversion with or without a duodenal switch (primarily malabsorptive operation), and the laparoscopic Roux-en-Y gastric bypass (considered a combination restrictive and selective malabsorptive procedure). Each operation has pros and cons. Important considerations, for the patient and surgeon alike, in the decision to proceed with bariatric surgery include the technical aspects of the operation, postoperative complications including long-term nutritional problems, magnitude of initial and sustained weight loss desired, and correction of obesity-related comorbidities. Herein, the pros and cons of the contemporary laparoscopic bariatric operations are reviewed and ongoing controversies relating to bariatric surgery are discussed: appropriate patient selection, appropriate operation selection for an individual patient, surgeon selection, and how to measure success after surgery.
PMCID: PMC3470459  PMID: 23091563
11.  The CNS and bladder dysfunction 
The brain's role in the development and maintenance of bladder control is critical, although its precise role in patient-reported complaints such as urgency and urine leakage is unknown. Functional brain imaging studies have advanced our knowledge of brain activity during the micturition cycle, showing multiple neuronal circuits involved as parts of a ‘brain-bladder control network.’ Yet, new advances need to be made in order to incorporate this knowledge into existing models of neuroanatomy and of clinical syndromes of bladder dysfunction and related clinical practice. This short article explains why and how brain imaging methods are poised to achieve that goal and decode the role of the brain in widely prevalent clinical conditions related to bladder dysfunction.
PMCID: PMC3470460  PMID: 23091564
12.  Sight restoration 
Cases of sight onset after extended periods of congenital blindness provide windows into visual development and brain plasticity. Such cases are extremely rare in the developed world. Here, we make the argument that in meeting a public health challenge in the developing world, that of providing treatment to curably blind children, we have the opportunity to have a beneficial impact on science and society simultaneously. A recent initiative, Project Prakash, is motivated by these twin goals. We briefly describe this effort, some of its early results, and also the caveats that need to be kept in mind when interpreting the findings.
PMCID: PMC3438651  PMID: 22991579
13.  New therapeutic approaches for malignant glioma: in search of the Rosetta stone 
Malignant gliomas are heterogeneous, diffuse and highly infiltrating by nature. Despite wide surgical resection and improvements in radio- and chemotherapies, the prognosis of patients with glioblastoma multiforme remains extremely poor, with a median survival time of only 14.5 months from diagnosis to death. Particular challenges for glioblastoma multiforme therapy are posed by limitations in the extent of feasible surgical resections, distinct tumor heterogeneity, difficulties in drug delivery across the blood-brain barrier and low drug distribution within the tumor. Therefore, new paradigms permitting tumor-specific targeting and extensive intratumoral distribution must be developed to allow an efficient therapeutic delivery. This review highlights the latest advances in the treatment of glioblastoma multiforme and the recent developments that have resulted from the interchange between preclinical and clinical efforts. We also summarize and discuss novel therapies for malignant glioma, focusing on advances in the following main topics of glioblastoma multiforme therapy: immunotherapy, gene therapy, stem cell-based therapies and nanotechnology. We discuss strategies and outcomes of emerging therapeutic approaches in these fields, and the main challenges associated with the integration of discoveries that occur in the laboratory into clinical practice.
PMCID: PMC3438652  PMID: 22991580
14.  Surrogate insulin-producing cells 
Diabetes, a large and growing worldwide health concern, affects the functional mass of the pancreatic beta cell, which in turn affects the glucose regulation of the body. Successful transplantation of cadaveric islets and pancreata for patients with uncontrolled type 1 diabetes has provided proof-of-concept for the development of commercial cell therapy approaches to treat diabetes. Three broad issues must be addressed before surrogate insulin-producing cells can become a reality: the development of a surrogate beta-cell source, immunoprotection, and translation. Cell therapy for diabetes is a real possibility, but many questions remain; through the collaborative efforts of multiple stakeholders this may become a reality.
PMCID: PMC3412316  PMID: 22891077
15.  Active surveillance for low-risk prostate cancer 
Active surveillance for localized prostate cancer entails initial expectant management rather than immediate therapy, with “curative-intent” treatment deferred until there is evidence that the patient is at increased risk for disease progression. This is a response to the clearly documented risks of over diagnosis and overtreatment of low-risk prostate cancer, which in most cases poses little or no threat to the patient. It is based upon the prolonged natural history of prostate cancer and is an attempt to balance the risks and side effects of overtreatment against the possibility of disease progression and a lost opportunity for cure. Low-risk prostate cancer is more accurately viewed as one of multiple risk factors for the presence of higher grade prostate cancer. Like atypical small acinar proliferation, (ASAP), it may be managed with close follow up but without radical intervention, unless there is clear evidence of more aggressive disease.
PMCID: PMC3412317  PMID: 22891078
16.  Stressing the heart of the matter: re-thinking the mechanisms underlying therapeutic effects of n-3 polyunsaturated fatty acids 
Despite their clear therapeutic effects in coronary heart disease, use of n-3 polyunsaturated fatty acids (PUFAs) to treat other types of cardiovascular disease remains controversial, and serious obstacles exist in implementing them as a reliable and consistent drug therapy. The foremost of these is that a molecular mechanism and relevant dosages have not been firmly established in other forms of cardiovascular disease. In this brief review, we highlight the current state of knowledge regarding the mechanisms behind n-3 PUFA action in the cardiovascular system. We also propose the novel hypothesis that lipid peroxidation products derived from n-3 PUFAs may be driving much of their beneficial cardiovascular effects, particularly in the myocardium. We conclude by discussing evidence to support this hypothesis, and its possible clinical ramifications.
PMCID: PMC3391752  PMID: 22802872
17.  The future of genomics in pathology 
The recent advances in technology and the promise of cheap and fast whole genomic data offer the possibility to revolutionise the discipline of pathology. This should allow pathologists in the near future to diagnose disease rapidly and early to change its course, and to tailor treatment programs to the individual. This review outlines some of these technical advances and the changes needed to make this revolution a reality.
PMCID: PMC3391753  PMID: 22802873
18.  Advances in dermoscopy for detecting melanocytic lesions 
Over the last 30 years dermatological approaches to diagnosis and management of melanocytic lesions have been revolutionized by the introduction of dermoscopy. Continuous improvements are being made in applying the technique, mostly in melanoma diagnosis, follow-up of melanocytic lesions and nevogenesis. Identification of new dermoscopic criteria, such as the dermoscopic island and the blue-black color for thin and nodular melanoma, respectively, further add two new weapons in the dermoscopical armamentarium for diagnosis of otherwise featureless melanoma. Recent advances show that short-term, 3-month, follow-up is the optimum time interval to identify minimal changes in initially featureless melanomas. Nevertheless, long-term follow-up is still useful for the recognition of changes in melanomas with a very low-rate of growth. Dermoscopy greatly improves diagnosis and early excision of melanomas and reduces the number of unnecessary excisions.
PMCID: PMC3370664  PMID: 22719794
19.  New drugs to treat tuberculosis 
Tuberculosis (TB) has been a leading cause of death for more than a century. While effective therapies exist, treatment is long and cumbersome. Tuberculosis control is complicated by the overlapping problems created by global inadequacy of public health infrastructures, the interaction of the TB and human immunodeficiency virus epidemics, and the emergence of drug-resistant TB. After a long period of neglect, there is now significant progress in development of TB diagnostics and therapeutics. Focusing on treatment for active TB, we review the new pathways to TB regimen development, and the new and repurposed anti-TB agents in clinical development.
PMCID: PMC3370665  PMID: 22719795
20.  Advances in the Diagnosis and Treatment of Acute Pulmonary Embolism 
Over the past two decades, considerable progress in technology and clinical research methods have led to advances in the diagnosis, treatment and prevention of acute venous thromboembolism. Despite this, however, the diagnosis is still often missed and preventive methods are often ignored. Published guidelines are useful, but are limited by the existing evidence base so that controversies remain with regard to topics such as duration of anticoagulation, indications for placement and removal of inferior vena caval filters, and when and how to administer thrombolytic therapy. The morbidity and mortality of this disease remain high, particularly when undiagnosed. While preventive approaches remain crucial, the focus of this review is on the diagnostic and therapeutic approach to acute venous thromboembolism, with an emphasis on acute pulmonary embolism.
PMCID: PMC3357009  PMID: 22619694
21.  Molecular Beacons in Diagnostics 
Recent technical advances have begun to realize the potential of molecular beacons to test for diverse infections in clinical diagnostic laboratories. These include the ability to test for, and quantify, multiple pathogens in the same clinical sample, and to detect antibiotic resistant strains within hours. The design principles of molecular beacons have also spawned a variety of allied technologies.
PMCID: PMC3357010  PMID: 22619695
22.  Telomeres in disease 
Telomeres and telomere repair are basic molecular features of cells possessing linear DNA chromosomes and defects in them result in various diseases. This review examines recent advances in understanding these diseases, particularly at a molecular level, and in relating telomere dysfunction to clinical diseases. We also discuss the potential role of telomere elongation as a therapy in diseases, and more controversially, the prevention/reversal of aging.
PMCID: PMC3318193  PMID: 22500192
23.  Helicobacter pylori: Eradication or Preservation 
Helicobacter pylori infects about 50% of the world’s population and inevitably results in the development of gastritis. Of those infected, about 10% develop peptic ulcer disease and roughly 1% develop gastric cancer. Conversely, some take the view that H. pylori infection provides some protection against gastro-esophageal reflux disease and possibly asthma. This review aims to explore the case for and against eradication of the bacterium using a “test and treat” approach amongst the general population.
PMCID: PMC3318258  PMID: 22500191
24.  Cognitive behaviour therapy for schizophrenia 
Schizophrenia is one of the major and potentially severe mental illnesses. Even with best practices, there are limitations to the effectiveness of treatments that include medications for this disorder. Relapse rates are high and often those with the illness remain symptomatic and functionally impaired. All the evidence suggests that individuals with schizophrenia do best with a combination of pharmacological and psychosocial intervention. One psychosocial treatment that has received much attention is cognitive behaviour therapy (CBT). This brief review will address what we know about the use and effectiveness of CBT at all phases of schizophrenia and its strengths, weaknesses and its future.
PMCID: PMC3292287  PMID: 22403587
25.  Kinase inhibitors in the treatment of immune-mediated disease 
Protein kinases are fundamental components of diverse signaling pathways, including immune cells. Their essential functions have made them effective therapeutic targets. Initially, the expectation was that a high degree of selectivity would be critical; however, with time, the use of “multikinase” inhibitors has expanded. Moreover, the spectrum of diseases in which kinase inhibitors are used has also expanded to include not only malignancies but also immune-mediated diseases. At present, thirteen kinase inhibitors have been approved in the United States, all for oncologic indications. However, there are a growing number of molecules, including several Janus kinase inhibitors, that are being tested in clinical trials for autoimmune diseases such as rheumatoid arthritis, psoriasis and inflammatory bowel diseases. It appears likely that this new class of immunomodulatory drugs will have a major impact on the treatment of immune-mediated diseases in the near future.
PMCID: PMC3297200  PMID: 22403586

Results 1-25 (249)