Giant cell arteritis: diagnosing and treating inflammatory disease in older adults

Giant cell arteritis (GCA), also known as temporal arteritis, cranial arteritis, or granulomatous arteritis, is a systemic necrotizing vasculitis seen in patients typically over age 50. If untreated, GCA can cause permanent visual loss in one or both eyes in 13% to 50% of patients. Primary care physicians routinely see elderly patients with headaches and fatigue; these may be potential symptoms of GCA. C-reactive protein (CRP) in conjunction with erythrocyte sedimentation rate (ESR) has 97% specificity in diagnosing GCA. Temporal artery biopsy confirms the diagnosis in many cases. Early recognition and treatment of this potentially blinding condition is thus essential. Systemic steroids are the standard therapy for patients with a positive diagnosis of GCA, and in a high percentage of patients the treatment may extend for more than one year.     

Short- and intermediate-term follow-up results of percutaneous transluminal balloon valvuloplasty in adolescents and young adults with congenital pulmonary valve stenosis

Percutaneous pulmonary balloon valvuloplasty (PBV) is a well-established treatment alternative to surgery in many cardiology centers. We described our experience with PBV in 25 adolescent and young adult patients with isolated pulmonary valve stenosis (PVS). Among 20 successful PBVs, there was a significant immediate decrease in right ventricular systolic pressure from 116.9 32.4 mmHg to 60.5 18.7 mmHg (p < 0.0001) and a decrease in transpulmonary valve pressure gradient from 93.5 32.8 mmHg to 33.5 9.7 mmHg (p < 0.0001) was noted. The follow-up period was 1-5 years (mean = 3.2 1.2 years), during which patients were periodically assessed by Doppler echocardiogram. During follow-up, the transpulmonary valve pressure gradient further decreased from 33.5 9.7 mmHg to 18.6 3.4 mmHg (p < 0.0001) mainly due to regression of infundibular hypertrophy. Thus, the study showed excellent short-term and intermediate-term results of PBV.     

Characteristics of Unscheduled and Scheduled Outpatient Palliative Care Clinic Patients at a Comprehensive Cancer Center

Context

There is limited literature regarding outpatient palliative care and factors associated with unscheduled clinic visits.

Prevalence of hypertension,control of blood pressure and treatment in hypertensive with type 2 diabetes in Hospital University Sains Malaysia

AimsTo determine the prevalence of hypertension, control of hypertension and patterns of antihypertensive medications in Malaysian type 2 diabetic patients who attended diabetes clinics in Hospital University Sains Malaysia (Tertiary Hospital).Materials and methodsThe study design was observational prospective longitudinal follow-up study; the study was conducted with sample of 1077 type 2 diabetes mellitus outpatient recruited whom attended the diabetes clinics at Hospital Universiti Sains Malaysia (HUSM) in Kelantan. The study period was from January till December 2008. Blood pressure was defined as >130/80 or use of antihypertension medications. Demographic characteristics of patients, level of blood pressure control, use of antihypertensive medications and patterns of antihypertensive therapy.ResultsThe prevalence of hypertension in Malaysian type 2 diabetic patients was 998 (92.7%),antihypertensive drugs were prescribed in 940 (94.2%) of hypertensive patients with type 2 diabetic mellitus. The achievement of blood pressure control (≤130/80 mmHg) was 471 (47.2%) %. The percentage of patients receiving one, two, three, and four drugs were 253 (25.3%), 311 (31.3%), 179 (17.9%), and 197 (19.7%) respectively. Calcium channel blockers were the most commonly prescribed antihypertensive agents 757 (75.7%) followed by Angiotensin-converting enzyme inhibitors 446 (44.6%), and Angiotensin receptor blockers 42.4 (42.4%).ConclusionThe prevalence of hypertension is high in Malaysian type 2 diabetic patients, hypertension was not controlled to the recommended levels of blood pressure in about one-half (52.8%) of diabetes patients. Calcium channel blockers were the most commonly prescribed antihypertensive agents. There is an urgent need to educate both patients and health care providers of importance of achieving target of treatment in order to reduce morbidity and mortality due to diabetes with hypertension.     

An extended treatment protocol with pegylated interferon and ribavirin for hepatitis C recurrence after liver transplantation

AIM: To evaluate the efflicacy and tolerability of an extended treatment protocol and to determine the predictors of sustained virological response (SVR) after liver transplantation (LT).METHODS: Between August 2005 and November 2008, patients with recurrent hepatitis C virus (HCV) after LT were selected for treatment if liver biopsy showed at least grade 2 inflammation and/or stage 2 flibrosis. All patients were to receive pegylated interferon (PEG)/regimens combining ribavirin (RBV) for an additional 48 wk after HCV undetectability.RESULTS: Extended protocol treatment was initiated in thirty patients. Overall, 73% had end of treatmentresponse and 60% had SVR. Nineteen patients completed treatment per protocol, of them, sixteen (84%) had end of treatment response, and fourteen (74%) achieved SVR. Both early virological response and 24-week virological response were individually associated with SVR but this association was not signif icant on multivariate analysis. Eleven patients (37%) discontinued therapy due to adverse effects. Cytopenias were the most common and most severe adverse effect, and required frquent growth factor use, dose adjustments and treatment cessations. The risk of rejection was not increased.CONCLUSION: Recurrent HCV after LT can be safely treated with extended virological responseguided therpy using PEG/RBV, but requires close monitoring for treatment-related adverse effects, particularly cytopenias.     

Overexpression of FoxM1 offers a promising therapeutic target in diffuse large B-cell lymphoma

Background

FoxM1 has been shown to play a critical role in the pathogenesis of various epithelial malignancies. However, its role in lymphoid malignancies has not been fully clarified. We, therefore, investigated the role of FoxM1 expression in a large cohort of diffuse large B-cell lymphoma samples and panel of cell lines.

Design and Methods

FoxM1 expression was investigated in a large series of diffuse large B-cell lymphoma tissues in a tissue microarray format by immunohistochemistry. Apoptosis was measured by flow cytometry and protein expression was detected by immunoblotting using diffuse large B-cell lymphoma cell lines following treatment with either pharmacological inhibitor of FoxM1 or small interference RNA knockdown strategy. Invasion/migration and soft agar colony assays were also performed following treatment with FoxM1 inhibitor.

Results

FoxM1 expression was detected in 84.6% of diffuse large B-cell lymphoma tumors and found to be significantly associated with proliferative tumor marker Ki67 (P<0.0001), matrix metalloproteinases-2 (P=0.0008), matrix metalloproteinases-9 (P=0.0002), S-phase kinase associated protein-2 (P<0.0001) and inversely associated with p27 expression (P=0.0215). Expression of small interference RNA targeted against FoxM1 or treatment of diffuse large B-cell lymphoma cells with thiostrepton caused its downregulation accompanied by decreased expression of matrix metalloproteinases-2 and matrix metalloproteinases-9. Inhibition of FoxM1 in diffuse large B-cell lymphoma cells also decreased invasive and migratory capability, and induced caspase dependent apoptosis via activation of the mitochondrial apoptotic pathway. Finally, combined thiostrepton and bortezomib at sub-toxic doses led to efficient apoptosis in diffuse large B-cell lymphoma cells.

Conclusions

Altogether, these results suggest that FoxM1 is over-expressed in the majority of diffuse large B-cell lymphoma samples. These data also indicate that targeting FoxM1 signaling can serve as a potential therapeutic modality in the management of diffuse large B-cell lymphoma.     

Determinants of successful medical education of caregivers of children with congenital heart diseases

Objective

To assess the implementation and efficiency of medical education among the caregivers of children with congenital heart disease (CHD) and to investigate its success factors.

Spectrum of beta-thalassemia mutations in various regions of Punjab and Islamabad, Pakistan: establishment of prenatal diagnosis

We present here an analysis of 888 unrelated beta-thal chromosomes consisting of 444 transfusion dependent children from various regions of Punjab and Islamabad Pakistan. By using Multiplex ARMS- PCR, restriction endonuclease analysis, allele specific oligonucleotide (ASO) hybridization and sequencing, 17 beta-thal mutations and 3 Hb variants were detected in 99.5 % (884/888) of the chromosomes analyzed. First trimester prenatal diagnosis by chorionic villus sampling (CVS) was also carried out in seven pregnancies at risk of beta-thalassemia. Our results indicate that three most common mutations accounted for 86.8% of the beta-thal alleles in this region. These findings have important implications for prevention of beta-thalassemia through genetic counseling and prenatal diagnosis in this part of Pakistan.     

Lupus nephritis. Clinicopathological correlation

OBJECTIVE: To classify all renal biopsies of lupus nephritis patients presenting in the last 10 years, according to the modified World Health Organization (WHO) classification using the facilities of light, fluorescent, and electron microscopy. To assess the activity and chronicity indices of renal biopsies according to the National Institute of Health protocol, and to correlate the histological findings with the clinical features of the patients presented up to the time of biopsy. METHODS: Seventy-eight patients with lupus nephritis, biopsied over 10 years between January 1995 to December 2005 in King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia were reviewed by 2 histopathologists with the assistance of a nephrologist. RESULTS: The predominant histological type was WHO class IV. Patients of this class were more commonly associated with microhematuria, elevated proteinuria, and renal insufficiency. Active and chronic lesions were more likely to occur in patients of class III/IV. These patients were also more likely to have evidence of clinical renal disease than patients in class II. There was a significant association between nephrotic syndrome and class V lupus nephritis. CONCLUSION: Although the clinical and pathological correlation demonstrated a significant relationship between underlying histopathology and the clinical course of the patient, however, the biopsy findings did not uniformly correlate with the clinical features. Moreover, the status prediction of lupus nephritis patients based on clinical information alone was significantly enhanced by information obtained from renal biopsy.