Combining etanercept with traditional agents in the treatment of psoriasis: a review of the clinical evidence

Psoriasis is a chronic, systemic inflammatory disorder manifesting primarily in skin and potentially in joints, frequently necessitating treatment with conventional systemic therapies, phototherapy or biological agents. Patients with moderate to severe disease suffer a diminished quality of life, experience significant comorbidities and have a higher mortality. Although traditional treatments are effective in the short‐term, their use is often limited by concerns over long‐term toxicity, including end‐organ damage and risk of malignancy. Combination therapy is a commonly used approach and is often more effective than any single agent. Lower doses of two treatments in combination can also minimize potential side effects from a single agent at higher doses. Etanercept is a recombinant human tumour necrosis factor (TNF)α receptor (p75) protein fused with the Fc portion of IgG1 that binds to TNFα. This article reviews the evidence on the efficacy and safety of etanercept in combination with methotrexate, acitretin, narrowband UVB and cyclosporin. The largest body of evidence assesses the combination with methotrexate, although evidence is available for the other combinations. Data suggest that although highly effective as monotherapy, etanercept in combination with a conventional systemic agent can enhance efficacy and allow drug sparing. Potentially, the combination may also result in faster treatment responses and permit safe transitioning from one systemic agent to another. Evidence to date suggests that these benefits can be achieved without significant additional toxicity, although long‐term data on the efficacy and safety of the combination in psoriatic populations is limited and further evaluation is warranted.     

Extracranial schwannoma of the maxillary nerve misdiagnosed as trigeminal neuralgia in an elderly patient with schizophrenia – A diagnostic dilemma

The present paper discusses the diagnostic challenges we faced in a 60-year-old woman with a history of schizophrenia, presenting with left unilateral facial pain for the past three months. Based on the elaborate clinical examination and diagnostic nerve blocks, the patient was diagnosed with trigeminal neuralgia (TN) and non-surgical therapy commenced. Further investigations with magnetic resonance imaging (MRI) and ultrasound-guided fine needle aspiration cytology (FNAC) revealed the presence of an extracranial schwannoma involving a branch of the maxillary nerve. The patient was symptomatically relieved after surgical excision of the benign tumor under general anesthesia. Hence, we emphasize the need for special care and attention in psychiatric patients presenting with orofacial pain.     

Human jaw-opening muscle responses elicited by multiple-site electrical stimulation

Electrical stimuli were applied to subjects' upper and/or lower gingivae around the right canines; (i) during maintained relaxation of masticatory muscles; (ii) at an active opening position; (iii) while clenching in an incisal edge-to-edge contact (IEC) position; and (iv) at the wide-open position. Reflex responses of the suprahyoid and jaw-closing muscles were obtained using surface electrodes. The electrical stimulation produced segmented reflex excitation(s) in the suprahyoid muscle and conventional reflex excitation and/or inhibition in the jaw-closing muscles when some background activity was maintained in the muscle(s). The excitatory reflex in the suprahyoid muscle responded to multiple site electrical stimulation which was delivered on both the upper and lower jaw simultaneously rather than to single site stimulation. Also, the responses depended on the intensity of the electrical stimulation. In particular, stronger intensities resulted in longer latencies. The results support the suggestions in our previous studies with mechanical stimuli, i.e. that the human jaw-opening reflex can be obtained only when some background activity is maintained in the jaw openers, perhaps due to low threshold afferent input, and that spatial summation may be effective for the reflex.     

Genetic analysis of thermolabile methylenetetrahydrofolate reductase as a risk factor for myocardial infarction

Hyperhomocyst(e)inemia is associated with an increased risk of coronary artery disease and myocardial infarction. Both genetic and environmental factors influence the plasma level of homocysteine. One of the metabolic pathways for homocysteine involves the enzyme methylenetetrahydrofolate reductase (MTHFR), which regulates the conversion of homocysteine to methionine. A thermolabile variant of MTHFR is associated with reduced enzyme activity and increased plasma homocysteine levels. Recently, the cause of this variant of MTHFR has been identified as a single base change altering an alanine to a valine residue in the protein. Using a PCR-based assay to distinguish the normal and thermolabile variants of MTHFR in this study, we investigated whether the thermolabile variant is a genetic risk factor for myocardial infarction. In a study of 532 subjects (310 myocardial infarction patients and 222 population-based controls), we found no difference in either MTHFR genotype distribution (<it>p</it> = 0.57) or allele frequencies (<it>p</it> = 0.68) between cases and controls. The allele frequencies of the thermolabile variant were 0.34 and 0.35 in cases and controls, respectively. The age- and sex-stratified odds ratio for risk of myocardial infarction associated with homozygosity for the thermolabile variant was 0.85 (95% CI 0.50-1.50, <it>p</it> = 0.57) and that with carriage of the thermolabile allele was 1.06 (95% CI 0.73-1.52, <it>p</it> = 0.76). The odds ratio remained non-significant when restricted to young subjects (&lt;60 years) or males, and were not influenced by several other risk factors for myocardial infarction considered either singly or in combination. Interestingly, in both cases and controls, there was a trend toward a higher prevalence of hypertension in subjects carrying the normal allele, although as this is a <it>post-hoc</it> finding it needs to be interpreted with caution. The thermolabile variant of MTHFR is not a major risk factor for myocardial infarction and is unlikely to explain a significant proportion of the reported association of hyperhomocyst(e)inemia with coronary artery disease.      

Development of parvalbumin immunoreactive neurons in normal and intracranially transplanted retinas in the rat

Summary Retinas from embryonic day 14 Sprague-Dawley rats were transplanted to the midbrain or cerebral cortex of newborn (P0) rats of which the right eye was enucleated at the time of transplantation. Parvalbumin immunoreactive (PV-I) neurons were studied in the developing retinal transplants, and in the remaining retina of the host, as well as in normal retinas. PV-I neurons were identifiable in retinas of normal and host rats from postnatal day 5 (P5) onward, with the PV-I somata primarily in the inner half of the inner nuclear layer and in the ganglion cell layer. An adult-like distribution of PV-I neurons was attained at P35, as judged by cell packing density, intensity of immunostaining, laminar distribution and soma size of subpopulations of PV-I cells. A similar time course of development and distribution of PV-I somata was observed in the retinal transplants, except for some minor differences such as a slight delay in PV-I cells achieving their final distribution. These findings provide evidence that PV-I neurons can survive, differentiate and mature according to pre-determined programmes intrinsic to the retinal tissue following transplantation to a new and foreign environment.Visiting research fellow on leave from the Neurosciences Research Institute, Guangzhou Medical College, People's Republic of China