Ocular toxoplasmosis following anti-tumour necrosis factor-α therapy combined with oral methotrexate therapy: A case report and review of literature.

Purpose: To report a case of ocular toxoplasmosis following long-term treatment with adalimumab and review the literature on ocular toxoplasmosis following anti-Tumour necrosis factor-α therapy. Method: A retrospective chart review of A 21-year-old male who developed retinochoroiditis in his left eye following adalimumab therapy combined with oral methotrexate. Result: A known patient of juvenile idiopathic arthritis (JIA) on adalimumab and oral methotrexate for the last four years presented to us with a blurring of vision for the last 15 days. Fundus examination of the left eye revealed severe vitritis and two patches of retinochoroiditis in the inferior part of the fundus. Subsequent investigations confirmed it to be a case of toxoplasma retinochoroiditis, and he responded to anti-toxoplasma treatment. A review of literature on a similar topic revealed five such cases, and the index case was the first such report in patients with JIA. Conclusion: The index case highlights the importance of early recognition and management of opportunistic infections in patients receiving biologicals.

Review of Biosimilars of Adalimumab.

A first fully humanized monoclonal antibody approved by US Food and Drug Administration (FDA) in 2002 was Adalimumab. Clinical efficacy and safety of adalimumab has been assessed in various trials in rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, Crohn's Disease, and ulcerative colitis. It is one of the major sales success among biological and still one of the greatest blockbuster amongst monoclonal antibodies. With the advent of patent expiry of the parent drug HUMIRA, several potential biosimilars have debuted in various markets worldwide. Present article will discuss current situation of molecules that are front-runners to become adalimumab biosimilars with particular stress on Indian market and ZRC3197 (Adalimumab Biosimilar).

Use of oil bodies and oleosins in recombinant protein production and other biotechnological applications.

Oil bodies obtained from oilseeds have been exploited for a variety of applications in biotechnology in the recent past. These applications are based on their non-coalescing nature, ease of extraction and presence of unique membrane proteins-oleosins. In suspension, oil bodies exist as separate entities and, hence, they can serve as emulsifying agent for a wide variety of products, ranging from vaccines, food, cosmetics and personal care products. Oil bodies have found significant uses in the production and purification of recombinant proteins with specific applications. The desired protein can be targeted to oil bodies in oilseeds by affinity tag or by fusing it directly to the N or C terminal of oleosins. Upon targeting, the hydrophobic domain of oleosin embeds into the TAG matrix of oil body, whereas the protein fused with N and/or C termini is exposed on the oil body surface, where it acquires correct confirmation spontaneously. Oil bodies with the attached foreign protein can be separated easily from other cellular components. They can be used directly or the protein can be cleaved from the fusion. The desired protein can be a pharmaceutically important polypeptide (e.g. hirudin, insulin and epidermal growth factor), a neutraceutical polypeptide (somatotropin), a commercially important enzyme (e.g. xylanase), a protein important for improvement of crops (e.g. chitinase) or a multimeric protein. These applications can further be widened as oil bodies can also be made artificially and oleosin gene can be expressed in bacterial systems. Thus, a protein fused to oleosin can be expressed in Escherichia coli and after cell lysis it can be incorporated into artificial oil bodies, thereby facilitating the extraction and purification of the desired protein. Artificial oil bodies can also be used for encapsulation of probiotics. The manipulation of oleosin gene for the expression of polyoleosins has further expanded the arena of the applications of oil bodies in biotechnology.

Schwannoma of the nasal septum.

Schwannomas of the nasal cavity and paranasal sinuses are very rare. We report the case of a 54-year-old woman with a schwannoma arising from the nasal septum. We discuss the clinical presentation, differential diagnosis, imaging characteristics and treatment of this rarely encountered lesion.

The role of magnetic resonance imaging in the assessment of suspected extrinsic tracheobronchial compression due to vascular anomalies.

AIMS: To evaluate the role of magnetic resonance imaging (MRI) in the assessment of children with suspected extrinsic tracheobronchial compression due to vascular anomalies. METHODS: Retrospective case note review in a tertiary referral centre. Twenty nine children who underwent dynamic laryngotracheobronchoscopy (DLTB) and were found to have a clinical suspicion of extrinsic tracheobronchial compression were evaluated. All subsequently underwent thoracic MRI within 10 days. The findings on endoscopy were compared to those of MRI, and where performed, echocardiography, aortography, and surgery. RESULTS: There were 17 males and 12 females (mean age 5 months, range 28 weeks gestation to 60 months). The most common presenting features were stridor and cyanotic episodes. MRI showed abnormalities in 21 patients. There were five vascular rings (three double aortic arches and two right aortic arches) and 11 cases of innominate artery compression. Other vascular anomalies noted included aberrant right subclavian artery and aneurysmal left pulmonary artery. Echocardiography was generally found to be unhelpful in the diagnosis of extra-cardiac vascular abnormalities. Angiography was subsequently conducted in eight children; findings agreed with those shown on MRI. Surgery was performed on all five vascular rings, one innominate artery compression, and one aneurysmal left pulmonary artery. Surgical findings were also compatible with the preoperative MRI. CONCLUSIONS: This study shows the successful use of MRI as the initial imaging modality in endoscopically suspected extrinsic vascular compression of the upper airway. It enables accurate delineation of vascular anomalies and, unlike aortography, is non-invasive and does not require the use of contrast media.

How we do it: adjunctive intravenous midazolam: diagnosis and treatment of therapy-resistant muscle tension dysphonia.

Dysphonic patients with muscle tension are common at voice clinics. The majority respond to intensive vocal therapy. A small number of cases remain resistant to intensive vocal therapy. We have used intravenous midazolam to enhance therapy-resistant dysphonic patients' self-monitoring, their self-awareness and to change fixed patterns. Six of seven patients were discharged with restoration of normal voice 1 month after treatment.

Conchopexy suture to prevent middle turbinate lateralisation and septal haematoma after endoscopic sinus surgery.

Endoscopic ethmoidectomy is now one of the commonest surgical procedures performed by ear, nose and throat surgeons. Access to the ethmoid air cells is via the middle meatus following medialisation of the middle turbinate and uncinectomy. The most satisfactory postoperative results are achieved by maintaining patency of the middle meatus. This allows delivery of topical medication and sinus aeration. Spontaneous lateralisation of the middle turbinate during the healing period, with or without synechiae, can compromise the surgical benefit. This paper describes a conchopexy suture placed at completion of ethmoidectomy. A carefully placed yet simple suture technique will maintain a widely patent middle meatus during the phase of post-operative healing. A slight modification allows quilting of mucoperichondrial flaps after septal surgery.

CDP-870 (certolizumab) in rheumatoid arthritis.

The development of biological anti-TNF-alpha therapy has revolutionised the treatment of rheumatoid arthritis and other inflammatory diseases, and has identified a worldwide market for expensive yet effective therapies for chronic diseases. Certolizumab (CDP-870) is a new agent that employs a novel strategy to neutralise TNF-alpha--namely the prokaryotic expression of TNF-alpha-specific Fab antibody fragments, coupled to polyethylene glycol--to produce a drug that is potentially less expensive to manufacture than other anti-TNF-alpha agents and which may be administered by subcutaneous injection once a month. The background to the ongoing development of this new agent and its clinical effects are discussed in this article.

A tubeless anaesthetic technique for paediatric laryngeal laser surgery.

Laser surgery on the paediatric larynx requires cooperation between the surgeon and anaesthetist to carry out the procedure in the safest manner possible. Over a period of 3 years, 45 laser procedures have been undertaken on the upper airway of 14 patients at our institution. All procedures were performed with volatile gas anaesthesia supplied via a nasopharyngeal tube in a spontaneously ventilating patient, thus allowing the surgeon an unobstructed view of the larynx. In only one case, was a problem experienced with the technique, that of laryngospasm. The technique provides an unrivalled view of the larynx whilst allowing safe anaesthesia.

Histiocytic necrotising lymphadenitis (Kikuchi's disease): a rare cause of cervical lymphadenopathy.

Both Head and Neck Surgeons and General Surgeons are frequently referred patients with cervical lymphadenopathy. An uncommon but important cause is histiocytic necrotising lymphadenitis. This is a benign self-limiting disease that has been confused with malignant lymphomas. Some patients may also experience distressing and debilitating symptoms which can last for months. We describe four cases to illustrate the varied clinical presentation of this disease and present new signs seen in association with it. A remarkable therapeutic response to a short course of oral corticosteroids was observed in one case.

AMPK as a metabolic switch in rat muscle, liver and adipose tissue after exercise.

UNLABELLED: An increasing body of evidence has revealed that activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK)-activated protein kinase increases fatty acid oxidation by lowering the concentration of malonyl coenzyme A (CoA), an inhibitor of carnitine palmitoyl transferase 1. Studies carried out primarily in skeletal muscle suggest that AMPK modulates the concentration of malonyl CoA by concurrently phosphorylating and inhibiting acetyl CoA carboxylase (ACC), the rate limiting enzyme in malonyl CoA synthesis, and phosphorylating and activating malonyl CoA decarboxylase (MCD), an enzyme involved in its degradation. We have recently observed that AMPK and MCD activities are increased and ACC activity diminished in skeletal muscle, liver and, surprisingly, in adipose tissue 30 min following exercise (treadmill run) in normal rats. In liver and adipose tissue these changes were associated with a decrease in the activity of glycerol-3-phosphate acyltransferase (GPAT), which catalyses the first committed reaction in glycerolipid synthesis and, which like ACC, is phosphorylated and inhibited by AMPK. Similar changes in ACC, MCD and GPAT were observed following the administration of 5-aminoimidazole 4-carboxamide-riboside (AICAR), further indicating that the exercise-induced alterations in these enzymes were AMPK-mediated. CONCLUSIONS: (1) AMPK plays a major role in regulating lipid metabolism in multiple tissues following exercise. (2) The net effect of its activation is to increase fatty acid oxidation and diminish glycerolipid synthesis. (3) The relevance of these findings to the regulation of muscle glycogen repletion in the post-exercise state and to the demonstrated ability of AMPK activation to decrease adiposity and increase insulin sensitivity in rodents remains to be determined.

Mechanism of suppression of cardiac L-type Ca(2+) currents by the phospholipase A(2) inhibitor mepacrine.

Phospholipase A(2) plays a crucial role in the release of arachidonic acid (AA) from membrane phospholipids and in myocardial injury during ischemia and reperfusion. Mepacrine, a phospholipase A(2) inhibitor, has been shown to protect the heart from ischemic injury. In order to examine the mechanism of this protection, we investigated the effects of mepacrine on the L-type Ca(2+) current (I(Ca,L)) in rat single ventricular myocytes. Extracellular application of mepacrine significantly inhibited I(Ca,L) in a tonic- and use-dependent manner. The inhibition was also concentration-dependent with an IC(50) of 5.2 microM. Neither the activation nor the steady-state inactivation of I(Ca,L) was altered by mepacrine. The mepacrine-induced inhibition of I(Ca,L) was reversible after washout of the inhibitor. Addition of 1 microM AA partially reversed the mepacrine-induced inhibition of I(Ca,L). Intracellular dialysis, with 2 mM cAMP, significantly increased I(Ca, L), but did not prevent the mepacrine-induced inhibition of I(Ca,L). In addition, extracellular application of isoproterenol or membrane permeable db-cAMP did not reverse the mepacrine-induced inhibition of I(Ca,L). Biochemical measurement revealed that incubation of ventricular myocytes with mepacrine significantly reduced intracellular cAMP levels. The mepacrine-induced reduction of cAMP production was abolished by addition of AA. Our results demonstrate that mepacrine strongly inhibits cardiac I(Ca,L). While mepacrine is a phospholipase A(2) inhibitor and reduces cAMP production, its inhibitory effect on I(Ca,L) mainly results from a direct block of the channel. Therefore, we speculate that the protective effect of mepacrine during myocardial ischemia and reperfusion mostly relates to its blockade of Ca(2+) channels.

Elevated cardiac troponin levels do not predict adverse outcomes in hospitalized patients without clinical manifestations of acute coronary syndromes.

The prognostic significance of elevated cardiac troponin levels (CTL) in hospitalized patients with no other evidence of myocardial ischemia or injury is largely unknown. Fifty patients (mean age 61 +/- 15 years, 15 women) out of 580 consecutive hospitalized patients were selected based on normal CK-MB and at least 3-fold increase of CTL. The medical charts of these patients were reviewed and a 1-year follow-up was performed. The most frequent admission diagnoses were exacerbation of congestive heart failure (22%), stroke (20%) followed by respiratory failure (6%), cirrhosis (6%), gastrointestinal bleeding (6%), end-stage renal disease (4%), atrial fibrillation (4%) and metastatic malignancies (4%). Abnormal CTL prompted a cardiology consult in 48% of patients, an echocardiogram in 44%, myocardial perfusion study in 10% and coronary angiography in 1 patient. Of 21 deaths, only 1 was related to an acute coronary event. The measurement of CTL in patients without definite clinical or electrocardiographic evidence of myocardial ischemia and with a wide spectrum of clinical diagnoses does not predict in-hospital and at 1 year cardiovascular complications and/or cardiac death.

Underuse and overuse of diagnostic testing for coronary artery disease in patients presenting with new-onset chest pain.

PURPOSE: To determine the extent of overuse and underuse of diagnostic testing for coronary artery disease and whether the socioeconomic status, health insurance, gender, and race/ethnicity of a patient influences the use of diagnostic tests. SUBJECTS AND METHODS: We identified patients who presented with new-onset chest pain not due to myocardial infarction at one of five Los Angeles-area hospital emergency departments between October 1994 and April 1996. Explicit criteria for diagnostic testing were developed using the RAND/University of California, Los Angeles, expert panel method. They were applied to data collected by medical record review and patient questionnaire. RESULTS: Of the 356 patients, 181 met necessity criteria for diagnostic cardiac testing. Of these, 40 (22%) failed to receive necessary tests. Only 7 (3%) of the 215 patients who received some form of cardiac testing had tests that were judged to be inappropriate. Underuse was significantly more common in patients with only a high school education (30% vs 15% for those with some college, P = 0.02) and those without health insurance (34% vs 15% of insured patients, P = 0.01). In a multivariate logistic regression model, only the lack of a post-high school education was a significant predictor of underuse (odds ratio 2.2, 95% confidence interval 1.0 to 4.4). CONCLUSION: Among patients with new-onset chest pain, underuse of diagnostic testing for coronary artery disease was much more common than overuse. Underuse was primarily associated with lower levels of patient education.

Aortic sinotubular atherosclerotic debris associated with cerebral embolic events can be identified by transthoracic echocardiography.

OBJECTIVE: To evaluate the association between the presence of aortic sinotubular debris (STAD) identified by transthoracic echocardiography (TTE) and embolic strokes. BACKGROUND: The presence of atherosclerotic debris in the ascending aorta or aortic arch detected by transesophageal echocardiography or epiaortic echocardiography has been well established to be correlated with embolic stroke or other thromboembolic events. No data are available on the role of TTE in describing aortic pathology in thromboembolic events. METHODS: We identified 60 transthoracic echocardiographic studies from 11,275 studies, in which STAD was diagnosed. The charts of these patients (group 1; mean age 67 +/- 10 years) were reviewed and compared with those of 57 patients (group 2) without STAD, matched for age, gender and risk factors for advanced atherosclerosis. The results of brain imaging procedures, carotid duplex and coronary angiography were also reviewed. RESULTS: Ischemic stroke was found in 15 of group 1 (25%) and 4 patients of group 2 (7%, odds ratio = 4.4; 95% confidence interval, 1.3-19.4, p = 0.008). The average thickness of STAD was 0.7 +/- 0.2 cm in stroke patients and 0.6 +/- 0.2 cm in patients without stroke (p = n.s.). STAD was associated with

Genotoxic effect of ammonia exposure on workers in a fertilizer factory.

Cytogenetic investigations carried out on 22 workers exposed to ammonia in a fertilizer factory showed increased frequency of chromosome aberrations (2.00) and sister chromatid exchanges (5.21). Effect of smoking and/or drinking habits coupled with exposure to ammonia showed higher values of mitotic index, satellite associations and micronuclei in the exposed workers (6.50, 17.4 and 2.20 respectively) as compared to the controls (4.34, 8.11 and 0.14 respectively). The results indicate the genotoxic potential of ammonia gas in the ambient air of the work place.

International perceptions and approval of gene therapy.

Gene therapy is in clinical trials in a number of countries, raising the question of whether different ethical standards can be justified in different countries. One key issue is how divergent are the perceptions and bioethical reasoning of peoples around the world. An International Bioethics Survey with 150 questions, including 35 open ones, was developed to look at how people think about diseases, life, nature, and selected issues of science and technology, biotechnology, genetic engineering, genetic screening, and gene therapy. The mail response survey was conducted in 1993 among the public in Australia, India, Israel, Japan, New Zealand, Russia, and Thailand, and the same written survey was conducted among university students in Australia, Hong Kong, India, Japan, New Zealand, The Philippines, Russia, Singapore, and Thailand. Similar questions were included in an international high school education bioethics survey among high school teachers in Australia, Japan, and New Zealand. Further international comparisons to the United States and Europe are made. About three-quarters of all samples supported personal use of gene therapy, with higher support for children's use of gene therapy. The diversity of views was generally similar within each country. The major reasons given were to save life and increase the quality of life. About 5-7% rejected gene therapy, considering it to be playing God, or unnatural. There was very little concern about eugenics (0.5-2%), and more respondents gave supportive reasons like "improving genes," especially in Thailand and India. Support for specific applications was significantly less for "improving physical characters," "improving intelligence," or "making people more ethical" than for curing diseases like cancer or diabetes, but there was little difference between inheritable or noninheritable gene therapy.