Reducing Flightless I expression decreases severity of psoriasis in an imiquimod-induced murine model of psoriasiform dermatitis.

BACKGROUND: Psoriasis is a common chronic skin condition characterized by excessive inflammation and aberrant epidermal proliferation. Flightless I (Flii) is an actin-remodelling protein that regulates these processes, suggesting a possible role in psoriasis. OBJECTIVES: We sought to determine whether a benefit in psoriasiform dermatitis might occur after modulating Flii gene expression or reducing its levels using neutralizing antibodies. METHODS: Biopsies of psoriatic skin lesions from patients were assessed for Flii levels. Psoriasis-like lesions were induced in Flii heterozygous (Flii+/- ), wild-type (Flii+/+ ) and Flii transgenic (FliiTg/Tg ) mice using topical application of imiquimod. Additionally, psoriasis-induced wild-type mice were treated with topical application of Flii neutralizing antibodies and erythema, inflammation and histology were assessed. RESULTS: Flii was elevated in psoriatic lesions from patients with psoriasis compared with normal human skin. Reducing Flii decreased erythema, inflammatory cell infiltrate, proinflammatory cytokines and the thickness of the epidermis. Topical application of Flii neutralizing antibodies to wild-type mice treated with imiquimod resulted in significantly reduced psoriasiform dermatitis. CONCLUSIONS: Flii is a novel target involved in psoriasiform dermatitis and reducing cutaneous Flii could potentially be a new approach for treating patients with psoriasis.

A review of multiple sclerosis with Asian perspective.

Multiple sclerosis, although a rare disease in Asia, often presents significant diagnostic challenges to clinicians. There has been rapid advancement in the understanding of the underlying genetic influence, pathophysiology, investigation and treatment recently. This paper reviewed the latest development of various aspects of the disease and examined the differences between the manifestations of Asian and Western patients. The implications of these differences to investigation and treatment were also touched upon.

Magnetic resonance imaging of Asians with multiple sclerosis was similar to that of the West.

Magnetic resonance imaging (MRI) of the brain is the most important paraclinical diagnostic test in multiple sclerosis (MS). The appearance of MRI in Asians with MS is not well defined. We retrospectively surveyed the first brain and spinal cord MRI in patients diagnosed to have MS, according to Poser's criteria in seven regions throughout Asia to define the MRI changes among Asians with MS. There were 101 patients with first brain, and 86 with first spinal cord MRI, 66 of whom had both. The brain MRI showed a mean of 17 lesions per patient in T2 weighted images, mostly asymptomatic. Almost all the lesions were in the white matter, particularly in the juxtacortical, deep and periventricular white matter. A third of the lesions were greater than 5 mm, 14% enhanced with gadolinium. There were more supratentorial than infratentorial lesions at a ratio of 7.5: 1. Ninety five percent of the spinal cord lesions were in cervical and thoracic regions, 34% enhanced with gadolinium. The lesions extended over a mean of 3.6 +/- 3.3 vertebral bodies in length. Fifty (50%) of the brain and 54 (63%) of the spinal MRI patients had the optic-spinal form of MS. The MRI of the optic-spinal and classical groups of patients were similar in appearance and distribution, except that the optic-spinal MS patients have fewer brain but longer and more severe spinal cord lesions. In conclusion, the brain and spinal cord MRI of Asian patients with MS was similar to that of the West, although, in this study, Asian MS patients had larger spinal cord lesions.

The past, present and future of imaging in multiple sclerosis.

Despite technological advances in imaging, multiple sclerosis (MS) remains a clinical diagnosis that is supported, but not replaced, by laboratory or imaging findings. However, imaging is essential in the current diagnostic criteria of MS, for prediction of the likelihood of MS for patients with clinically isolated syndromes, correlation with lesion pathology and assessment of treatment outcome. This article gives an overview of imaging in MS with particular emphasis on the role of MRI in various diagnostic imaging criteria. Novel imaging for MS using 3 Tesla field strengths, magnetization transfer imaging, diffusion tensor imaging, magnetic resonance spectroscopy and cell-specific contrast will be reviewed.

Rapid detection and serotyping of dengue virus by multiplex RT-PCR and real-time SYBR green RT-PCR.

INTRODUCTION: Dengue fever and dengue haemorrhagic fever currently rank highly among the newly-emerging infectious diseases, and are considered to be the most important arboviral disease worldwide. The definitive diagnosis is culture analysis, but practical considerations limit its use. Also, the period for viral detection is limited. Within a day or two after fever subsides, rising levels of antibodies interfere with viral cultures. An alternative to this quandary is the use of viral RNA detection assays. In our laboratory, a reverse transcriptase polymerase chain reaction (RT-PCR) assay was developed using a set of degenerate primers. METHODS: This multiplex RT-PCR assay was evaluated with 280 samples collected during the year 2003. These groups include prototype dengue virus (serotypes 1-4), acute serum from which the dengue virus was isolated, seronegative acute samples (culture negative) but whose convalescent samples seroconverted, and sera positive for other microbial diseases. This assay was then modified into a real-time SYBR Green RT-PCR assay. Sensitivity and specificity of both assays were compared. RESULTS: The multiplex RT-PCR assay was able to detect 134 samples whereas SYBR Green RT-PCR assay was able to detect 178 out of 306 samples. Both assays were 100 percent specific. Further analysis of 53 samples showed that the virus could be amplified at IgM positive/negative values of up to 4.2, and up to six days after onset of fever. The viral detection rate was inversely proportional to the day of fever onset as well as IgM values. CONCLUSION: The sensitivity and specificity of the conventional multiplex RT-PCR assay are 98.18 percent and 100 percent, respectively, and for the real-time SYBR Green assay, 99.09 percent and 100 percent, respectively. The melting curve analysis allows all four dengue serotypes to be discriminated based on distinct melting temperature value. The accuracy and speed of this multiplex RTPCR assay makes it a suitable test for the diagnosis of dengue and for epidemiological surveillance.

Plasmapheresis in the University of Malaya Medical Centre, Malaysia.

Over the past 3 decades, plasmapheresis has been used more extensively for a variety of neurological and hematological disorders. We undertook a retrospective review to ascertain its safety, efficacy, and factor(s) that predispose to poor outcome. We reviewed 117 plasma exchanges in 24 patients with a mean age of 43 +/- 15 years; half were male. A total of 79% of the patients had neurological diseases, and the most common were chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, and myasthenic crisis. Plasmapheresis was effective in 79% of the patients, especially for neurological indications. Complications occurred in 23% of the exchanges affecting 58% of the patients. Most complications were mild; sepsis was the most common (9.4% of exchanges), especially catheter related sepsis (6%), rash (4.3%), and hypotension (4.3%). Only 2 (8%) patients had severe complications that required mechanical ventilation. There were 5 mortalities (21%), 3 due to sepsis and 2 due to myocardial ischemia and arrhythmia, none of which occurred within 48 h of the last exchange. Patients with poor renal function had higher mortality. Overall, our figures agree with those from other institutions and indicate that plasma exchange is an effective and safe procedure, especially for a variety of neuroimmunological conditions.

Treatment of acute Nipah encephalitis with ribavirin.

Nipah virus, a newly identified paramyxovirus caused a severe outbreak of encephalitis in Malaysia with high fatalities. We report an open-label trial of ribavirin in 140 patients, with 54 patients who were managed prior to the availability of ribavirin or refused treatment as control. There were 45 deaths (32%) in the ribavirin arm; 29 deaths (54%) occurred in the control arm. This represents a 36% reduction in mortality (p = 0.011). There was no associated serious side effect. This study suggests that ribavirin is able to reduce the mortality of acute Nipah encephalitis.