Accessibility to biologics and its impact on disease activity and quality of life in patients with rheumatoid arthritis in Kuwait

Clinical Rheumatology - Biologics are indicated in rheumatoid arthritis (RA) in case of persistent high disease activity despite conventional disease-modifying anti-rheumatic drugs (cDMARDs) or...     

Spontaneous and provoked growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) concentration in patients with beta thalassaemia and delayed growth

Growth retardation in children with thalassaemia major is multifactorial. We studied the growth hormone (GH) response to provocation by clonidine and glucagon, measured the circulating concentrations of insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP3), and ferritin, and evaluated the spontaneous nocturnal (12 h) GH secretion in prepubertal patients with thalassaemia and age-matched children with constitutional short stature (CSS) (height SDS < -2, but normal GH response to provocation). The anatomy of the hypothalamic pituitary area was studied in patients with abnormal GH secretion using MRI scanning. Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon (8.8 +/- 2.3 micrograms/l and 8.2 +/- 3.1 micrograms/l respectively) than did controls (17.6 +/- 2.7 micrograms/l and 15.7 +/- 3.7 micrograms/l respectively). They had significantly decreased circulating concentrations of IGF-I and IGFBP3 (68.5 +/- 19 ng/ml and 1.22 +/- 0.27 mg/l respectively) compared to controls (153 +/- 42 ng/ml and 2.16 +/- 0.37 mg/l respectively). Seven of the thalassaemic children had a GH peak response of < 7 micrograms/l after provocation. Those with a normal GH response after provocation also had significantly lower IGF-I and IGFBP3 concentrations than controls. Analysis of their spontaneous nocturnal GH secretion revealed lower mean (2.9 +/- 1.77 micrograms/l) and integrated (2.53 +/- 1.6 micrograms/l) concentrations compared to controls (4.9 +/- 0.29 micrograms/l and 5.6 +/- 0.52 micrograms/l respectively). Five of them had mean nocturnal GH concentration < 2 micrograms/l and four had maximum nocturnal peak below 10 micrograms/l. These data denoted defective spontaneous GH secretion in some of these patients. MRI studies revealed complete empty sella (n = 2), marked diminution of the pituitary size (n = 4), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 7) in those patients with defective GH secretion (n = 9). Serum ferritin concentration was correlated significantly with the circulating IGF-I (r = -0.47, p < 0.01) and IGFBP3 (r = -0.43, p < 0.01) concentrations. These data prove a high prevalence of defective GH secretion in thalassaemic children associated with structural abnormality of their pituitary gland.     

Clinical features of epilepsy at 2 referral hospitals in Northern Iran

Objective:

To investigate the demographic and clinical characteristics of epilepsy in 2 referral hospitals in northern Iran.

Methods:

In this cross-sectional study, we evaluated 300 patients with the confirmed diagnosis of epilepsy referred to the Neurology clinics of 22-Bahman, and 17-Shahrivar Hospitals, Mashad, Iran, from April 2011 to December 2012. We collected and analyzed demographic and disease information.

Results:

The mean age of patients was 31.5 ± 15.3 years. The diagnosis of disease had been made approximately 10 months after the onset of symptoms, and the treatment gap was 28%. The most widely used anticonvulsants were sodium valproate, carbamazepine, and phenobarbital. Generalized seizure was seen in 78%, partial seizure in 22%, and a combination of them in 11% of patients. Tonic-colonic seizure (72%) was the most common type of generalized epilepsy, and secondarily generalized seizure was the most frequent type of partial epilepsy.

Conclusion:

The epidemiological features of epilepsy in our region with regard to age and gender are the same as other parts of the world. The generalized type is the most common form of epilepsy, with tonic-colonic seizures being the most frequent type in our area.Epilepsy is a common and chronic neurological disorder that affects individuals of all ages and is characterized by recurrent (2 or more) unprovoked epileptic seizures.1 Seizure is an episode of involuntary movement, which may involve a part of the body or the entire body (generalized) and may be accompanied by loss of consciousness and control of bowel or bladder function. Seizure episodes are caused by abnormal electrical discharge in a group of brain cells. The age-adjusted prevalence and incidence of epilepsy in the general population are approximately 5 per 1000 person-years, and 50 per 100,000 person-years.2 The lifetime prevalence rate of epilepsy in developed countries is 3.5 to 10.7 per 1,000 person-years.3,4 Epilepsy affects 50 million people worldwide.5 The prevalence and incidence of epilepsy and consequently its burden is higher in developing countries than in developed countries.6 Approximately 80% of patients with epilepsy live in developing countries and so 80% of the disease burden is attributed to developing countries.6 Detailed classification of seizures and epilepsy is essential to understanding its nature, with a rational plan of investigation and decision making regarding the timing and duration of treatment and choice of antiepileptic drug. As our country is a developing country, better understanding of epilepsy features could provide better management and control of disease, and so decrease the burden of it. As the epidemiological and clinical characteristics of epilepsy are not yet completely understood in Iran, this study aimed to investigate the demographic and clinical features of epilepsy in 2 referral hospitals in our region.     

Electrochemical properties of a tetrabromo-p-benzoquinone modified carbon paste electrode. Application to the simultaneous determination of ascorbic acid,dopamine and uric acid

The electrochemical study of a tetrabromo-p-benzoquinone modified carbon paste electrode (TBQ-MCPE), as well as its efficiency for electrocatalytic oxidation of ascorbic acid, dopamine and uric acid, is described. Cyclic voltammetry was used to investigate the redox properties of this modified electrode at various solution pH values and at various scan rates. Three linear segments were found with slope values of ?58.4 mV/pH, ?28.1 mV/pH and 0.0 mV/pH in the pH range 2.0–7.1, pH 7.1–9.0 and pH 9.0–11.0, respectively. The apparent charge transfer rate constant, k_s, and transfer coefficient, α, for electron transfer between TBQ and CPE were calculated as 3.79 ± 0.10 s^?1 and 0.55, respectively. The electrode was also employed to study the electrocatalytic oxidation of AA, using cyclic voltammetry, chronoamperometry and differential pulse voltammetry as diagnostic techniques. It has been found that the oxidation of AA at the surface of TBQ-MCPE occurs at a potential of about 430 mV less positive than that of an unmodified CPE. The diffusion coefficient of AA was also estimated using chronoamperometry. The kinetic parameters such as the electron transfer coefficient, α, and heterogeneous rate constant, $k_{\mathrm{h}}^{\prime }$, for oxidation of AA at the TBQ-MCPE surface was determined using cyclic voltammetry. Differential pulse voltammetry (DPV) exhibits two linear dynamic ranges and a detection limit of 0.62 μM for AA. In DPV, the TBQ-MCPE could separate the oxidation peak potentials of AA, DA and UA present in the same solution, though at the unmodified CPE the peak potentials were indistinguishable. This modified electrode was quite effective not only to detect AA, DA and UA, but also in simultaneous determination of each component concentration in the mixture.     

Retroperitoneal Fibrosis after Chemotherapy

We report the case of a patient with a non-Hodgkin lymphoma, who after a standard chemotherapy protocol, developed retroperitoneal fibrosis (RPF) in the absence of radiotherapy or other known causes. The final diagnosis was reached with the microscopic examination of tissue obtained by fine-needle aspiration and true-cut biopsy of the retroperitoneal mass. RPF can be related to chemotherapy alone.     

Interaction of the retinoblastoma protein (pRb) with the catalytic subunit of DNA polymerase delta (p125)

The retinoblastoma gene product (pRb) interacts with many cellular proteins to function in the control of cell division, differentiation, and apoptosis. Several pRb binding proteins complex with pRb through an amino acid sequence called the LXCXE motif. The catalytic subunit of DNA polymerase delta (p125) contains a LXCXE motif. To further study the biochemical function of this polymerase, we sought to determine if p125 interacts with pRb. Experiments using GST-pRb fusion proteins showed that p125 from breast epithelial (MCF10A) cell extracts associates with pRb. In addition, GST-p125 fusion proteins bound pRb from the same cell extracts. The pRb that associated with GST-p125 was largely unphosphorylated. Coimmunoprecipitation experiments using cell cycle synchronized cells revealed that p125 and pRb form a complex predominantly during G1 phase, the phase during which pRb is mostly unphosphorylated. In vitro phosphorylation of GST-pRb by the cyclin dependent kinases reduced the ability of p125 to associate with GST-pRh. Addition of the LXCXE containing protein SV40 large T antigen to GST-pRb blocks the ability of p125 to associate with pRb, suggesting that it may be through a LXCXE sequence by which p125 interacts with pRb. Finally, in vitro polymerase assays demonstrate that GST-pRb fusion protein stimulates DNA polymerase delta activity.