Modulating co-stimulation

The modulation of co-stimulatory pathways represents a novel therapeutic strategy to regulate autoimmune diseases. Auto-reactive CD4+ T cells play a critical role in initiating the immune response leading to inflammation and autoimmune diseases. Blocking co-stimulatory signals prevents T-cell activation, thus diminishing autoimmune responses and possibly preventing the progression of autoimmune disease. Blockade of several co-stimulatory pathways has been investigated in animal models and has led to clinical trials testing specific blocking agents in humans. In this review we will describe the role of co-stimulatory pathways, primarily the CD28-B7 pathway, in autoimmune diseases, and we will present in vivo and in vitro studies supporting the efficacy of co-stimulation blockade in animal models of autoimmune disease. Finally, we will discuss the clinical therapeutic efficacy of blocking monoclonal antibodies in preventing or reducing auto-antigen driven T-cell activation in humans with particular attention to the CD28/B7 pathway. Inhibiting co-stimulatory molecule interactions by using monoclonal antibodies seems to be an original approach to regulate autoimmune diseases in humans.     

Characteristics of patients with congenital clasped thumb: a prospective study of 40 patients with the results of treatment

Purpose  Congenital clasped thumb is a deformity that is associated with heterogeneous congenital anomalies and it has been addressed in many congenital syndromes. The aim of this study was to diagnose and evaluate cases of clasped thumb as regards the associated congenital anomalies and syndromes, and evaluation of the results of treatment of such cases. Methods  A prospective study on 40 patients with 73 clasped thumbs was done. All the patients’ data regarding their personal, family, pregnancy and developmental histories were recorded. All the patients were exposed to thorough clinical and radiological examination and genetic assessment. The cases were classified using the Tsuyuguchi et al. (J Hand Surg [Am] 10:613–618, 1985) classification into three types. Conservative treatment was adopted in ten hands, and surgical treatment was performed for 28 hands in 17 patients, with an average follow-up of 26 months. Results  Positive consanguinity was recorded in 57.5% of cases. Associated anomalies were recorded in 77.5% of cases. Type I was the most common one, followed by type III and then type II. Conservative treatment is effective in type I cases when presented early, and all patients were satisfied with the results of surgical treatment. Conclusions  We reported associated anomalies which are to our knowledge have not mentioned before in the literature which include; congenital blindness, radial deviation of the index finger and ventricular septal defect. We found that 68% of the patients had associated syndromes, and this has not been mentioned before. In this study, we found that there were no difference between type II and type III clasped thumb as regards the pathological findings, severity, the operative procedures, the treatment protocol and the operative results. Properly planned treatment gives satisfactory results.     

Effects of epinephrine on retinal and choroidal blood flow through different routes of drug administration

Epinephrine (1, 3 and 10 micrograms/kg) was found to increase retinal and choroidal blood flow (22, 49 and 67%) when it was administered intravenously. The increase in retinal and choroidal blood flow coincided well with the increase in systemic blood pressure (44, 65 and 96%, respectively). When epinephrine (2%) was instilled to the eyes topically the retinal and choroidal blood flow decreased (15%) while systemic blood pressure remained unchanged. It is suggested that the decrease in retinal and choroidal blood flow by topical epinephrine could be the cause of epinephrine maculopathy reported previously. L-Timolol (0.25%, topically) did not affect retinal and choroidal blood flow significantly.     

Aztreonam for treating meningitis caused by gram-negative rods

10 patients with meningitis due to unusual gram-negative organisms (Pseudomonas, Proteus, Salmonella and Klebsiella) were effectively treated with aztreonam. A detailed history and a thorough physical examination combined with careful laboratory testing resulted in accurate diagnosis and cure of all patients.     

Dexamethasone adjunctive treatment for tuberculous meningitis

During a 5-year period, 280 of 2010 patients admitted to the meningitis ward of a referral hospital in Cairo, Egypt, were clinically diagnosed as having tuberculous meningitis and were treated with either antituberculous chemotherapy and dexamethasone or antituberculous chemotherapy alone. Fatality rates and neurologic sequelae were compared for the 2 treatment groups in the 160 patients who had cerebrospinal fluid cultures positive for Mycobacterium tuberculosis. The overall mortality rate of 51% reflects the delay in receiving appropriate therapy (79% with symptoms for more than 2 weeks) and the severity of illness on admission (56% in coma, 39% drowsy). The fatality rate was significantly lower in the group receiving dexamethasone (43% vs. 59%, P less than 0.05), particularly in the drowsy patients (15% vs. 40% P less than 0.04), and in patients surviving long enough to receive at least 10 days of treatment (14% vs. 33%, P less than 0.02). Development of neurologic complications after initiation of therapy (4 vs. 10) and permanent sequelae (6 vs. 13) were significantly lower in the dexamethasone-treated group (P less than 0.02).     

Status,challenges and facilitators of consumer involvement in Australian health and medical research

Background  

The emergent international practice of involving consumers in health research is driven, in part, by the growing share of health research that can only be applied in and emerge from knowledge that is shaped by human values and societal contexts. This is the first investigation of its kind to identify the current prevalence, challenges, enabling factors and range of approaches to consumer involvement in health and medical research in Australia.     

Denervation of taste buds in the rabbit

Twenty-five rabbits were used to study the effect of glossopharyngeal nerve transection upon the number, size and cellular constitution of the taste buds. The glossopharyngeal nerve was cut on one side, the other being left undisturbed as a control. The animals were sacrificed in groups of three after 7, 10, 14, 21, and 30 days, and 2 and 4 months after the operation. Seven days after the operation the size and number of intragemmal cells were decreased in the taste buds. The taste pores with hairlets passing through them disappeared. The number of taste buds on circumvallate papillae decreased. After ten days taste buds in both types of papillae showed signs of degeneration. Fourteen days after the operation there was a marked decrease in size and number of taste buds. The circumvallate papillae now possessed no taste buds. After 21 days few taste buds were present in foliate gutters. These consisted of one or two sustentacular cells each. After 30 days there were no taste buds on foliate papillae, and thickness of the epithelium lining the gutters was decreased. Two or four months after denervation, the foliate gutters were shallow and some had become flattened. The importance of the gustatory nerve for development and maintenance of the normal status of the taste buds is discussed.