Nuclear DNA replication and repair in parasites of the genus Leishmania: Exploiting differences to develop innovative therapeutic approaches

Leishmaniasis is a common tropical disease that affects mainly poor people in underdeveloped and developing countries. This largely neglected infection is caused by Leishmania spp, a parasite from the Trypanosomatidae family. This parasitic disease has different clinical manifestations, ranging from localized cutaneous to more harmful visceral forms. The main limitations of the current treatments are their high cost, toxicity, lack of specificity, and long duration. Efforts to improve treatments are necessary to deal with this infectious disease. Many approved drugs to combat diseases as diverse as cancer, bacterial, or viral infections take advantage of specific features of the causing agent or of the disease. Recent evidence indicates that the specific characteristics of the Trypanosomatidae replication and repair machineries could be used as possible targets for the development of new treatments. Here, we review in detail the molecular mechanisms of DNA replication and repair regulation in trypanosomatids of the genus Leishmania and the drugs that could be useful against this disease.     

All is Not Lost: Utilizing Continuous Remote ILR Monitoring to Diagnose Syncope

A 63‐year‐old man with frequent unexplained syncope was implanted with a second generation remotely monitored implantable loop recorder for continuous electrocardiogram (ECG) monitoring. He had a subsequent syncopal episode and despite accidental destruction of his patient activator, vital ECG data from the event were transmitted wirelessly, enabling a cardiac arrhythmia to be excluded. This case highlights the benefit of remote monitoring in syncope assessment, as well as a transmission system that ensures prompt analysis of the ECG data and therefore rapid optimal patient management. (PACE 2010; 33:763–765)     

Are People with Intellectual Disabilities Represented in European Public Health Surveys?

Background Evidence suggests that people with intellectual disabilities experience secondary health conditions and report inequities in health status and access to health systems. Reliable information is essential to identify health disparities. A review of health interview and health examination surveys conducted in 17 European countries was undertaken to determine whether people with intellectual disabilities were represented. Method Using the online HIS HES database, 123 health surveys were scrutinized to determine whether they contained questions relevant to the Pomona 18 indicator set, and whether data could be extracted specifically on behalf of respondents with intellectual disabilities. Results Findings reveal that while items relating to 16 of the Pomona 18 health indicators were found in 123 of the surveys scrutinized, only nine surveys were identified as having potential to extract data on respondents with intellectual disabilities. Conclusion These findings have implications for those charged with the collection of comparable information about population health.     

Serum insulin patterns and the relationship between insulin sensitivity and glycaemic profile in women with polycystic ovary syndrome

Objective  To evaluate serum insulin levels and insulin sensitivity in women with polycystic ovary syndrome (PCOS) in relation to their glycaemic status.
Design  An observational study.
Setting  A tertiary-level reproductive health centre in Sri Lanka.
Sample  Infertile women diagnosed as having PCOS ( n  = 168) on the basis of the Rotterdam criteria were included in the study.
Methods  Glycaemic status and serum insulin values were assessed at fasting and at 2 hours after a 75-g oral glucose load and stratified as diabetes mellitus (DM) (10.12%), impaired glucose tolerance (IGT) (23.21%) and normoglycaemia (66.67%). The normoglycaemic group was restratified as groups A (10.7%), B (79.5%) and C (9.8%) on the basis of serum insulin levels, with group A having the lowest and group C the highest values. The Quantitative Insulin Sensitivity Check Index (QUICKI) scores of women with DM and IGT and those in groups A, B and C in the normoglycaemic category were compared.
Main outcome measures  Insulin sensitivity in these groups of women.
Results  Body mass index (BMI) exceeded 23 kg/m² in 77.38% of the women. In normoglycaemic women with PCOS, insulin sensitivity was highest in group A. In groups B and C, insulin sensitivities corresponded to those found for women with IGT and DM respectively. This pattern was also reflected in the BMI.
Conclusions  Normoglycaemic women with PCOS are heterogeneous regarding insulin sensitivity. The treatment offered to those with DM and IGT could be extended to subgroups B and C of normoglycaemic subjects. Normoglycaemic women with PCOS with high insulin sensitivity (group A) would not qualify for this treatment.     

Treatment of early rheumatoid arthritis

Recent advances in the understanding of the pathophysiology, aggressive treatment, and early detection of rheumatoid arthritis (RA) have changed the clinical, pathologic, and functional outcomes in patients with RA. Early aggressive treatment of RA has now become the norm in clinical practice rather than the use of the traditional pyramid approach of the last half of the twentieth century. Early treatment with monotherapy of traditional disease-modifying antirheumatic drugs (DMARDs) or biologics, combination traditional DMARD therapy and, especially, combination of biologic therapy and methotrexate, have revolutionized the treatment of RA, producing significant improvement in clinical, radiographic, and functional outcomes not seen previously. For the individual patient, we still cannot determine which medication or combination of medications will give the most complete response. There have been a number of recent, well-designed clinical trials that have tried to answer this question. Herein we review the evidence-based medicine that addresses these issues.     

Use of the Implantable Loop Recorder in Evaluation of Patients with Unexplained Syncope

Syncope is a complex symptom with multiple potential etiologies that can be difficult to establish. The major obstacles to diagnosis are the periodic and unpredictable nature of events and the high spontaneous remission rate. Short-term ECG monitoring often is unproductive when initial noninvasive testing is negative due to the low probability of recurrence during the brief monitoring period. Implantable loop recorders extend the ability to monitor cardiac patients, enhancing the diagnostic yield to as high as 85% in difficult to diagnose syncope. Several recent studies suggest that prolonged monitoring with an implantable loop recorder has a role in patients with syncope and conduction disturbances, negative tilt testing, and unexplained seizures, and may be superior to conventional testing with tilt and electrophysiologic studies. (J Cardiovasc Electrophysiol, Vol. 14, pp. S70-S73, September 2003, Suppl.)     

Inclusion of supine period in short-duration pH monitoring is essential in diagnosis of gastroesophageal reflux disease

Prolonged esophageal pH monitoring is the most accurate method for detecting abnormal gastroesophageal reflux (GER) in patients with gastroesophageal reflux disease (GERD). However, some investigators have found that short-duration postprandial pH monitoring in the upright position is also useful, while others have failed to find such results. Therefore, we have compared a 6-hr period of pH monitoring (3-hr postprandial period after daytime meal and 3-hr supine period) with a total 24-hr period in detecting abnormal gastroesophageal reflux. Sixty-five patients (44 men, mean age 41.3 years) with GERD and 16 healthy volunteers (11 men, mean age 34.3 years) underwent 24-hr pH monitoring according to a standard protocol. Various reflux parameters during 24-hr pH monitoring were compared with reflux parameters during the 6-hr period. Abnormal GER was detected in 56 patients presenting with typical symptoms of GERD (sensitivity 86.2%). These patients could be further divided into upright (N=18), supine (N=15), and combined (N=23) refluxers, depending on the posture in which abnormal reflux occurred. Esophageal pH monitoring during the 3-hr postprandial upright period showed abnormal reflux in only 35 patients (sensitivity 53.8%;P<0.00005, compared with the 24-hr pH monitoring period). Abnormal GER was identified in 13 of 18 upright, 19 of 23 combined, and only one of 15 supine refluxers, as well as in two of nine patients with normal 24-hr pH-metry. However, inclusion of the 3-hr supine monitoring period in the 3-hr postprandial upright period improved detection of abnormal GER to 78.5% (51 patients;P=NS compared with 24-hr pH monitoring period). This was related mainly to improved detection of abnormal GER in supine refluxers (11 of 15; 73.3%). Esophageal acid exposure time correlated significantly with severity of esophagitis only during the total and supine periods of both the 24- and 6-hr periods and not during the upright period. Esophageal acid clearance correlated significantly with increasing grades of esophagitis for the supine and total periods only. We conclude that 3-hr postprandial pH monitoring, as has been conventionally practiced, is not appropriate in the detection of abnormal GER; inclusion of a supine period in the short-duration pH monitoring schedule increases the detection of pathological reflux. We therefore recommend that a supine period should be included in short-duration pH monitoring schedules. We also found that supine reflux was the most important factor in the development of esophagitis.     

Evidence‐based recommendations for the monitoring and treatment of ankylosing spondylitis: results from the Australian 3E initiative in rheumatology

Aim: To develop a set of Australian recommendations for the monitoring and treatment of ankylosing spondylitis (AS) through systematic literature review combined with the opinion of practicing rheumatologists. Methods: A set of eight questions, four in each domain of monitoring and treatment, were formulated by voting and the Delphi method. The results of a systematic literature review addressing each question were presented to the 23 participants of the Australian 3E meeting. All participants were clinical rheumatologists experienced in the daily management of AS. Results: After three rounds of breakout sessions to discuss the findings of the literature review, a set of recommendations was finalized after discussion and voting. The category of evidence and strength of recommendation were determined for each proposal. The level of agreement among participants was excellent (mean 84%, range 64–100%). Conclusions: The 12 recommendations developed from evidence and expert opinion provide guidance for the daily management of AS patients. For most recommendations, we found a paucity of supportive evidence in the literature highlighting the need for additional clinical studies.     

A prospective study of oesophageal 24-h ambulatory pH monitoring in patients with functional dyspepsia

BACKGROUND: The diagnostic utility of 24-h oesophageal ambulatory pH monitoring in patients with functional dyspepsia has not been well established. AIMS: We performed a prospective study of oesophageal pH monitoring in patients with functional dyspepsia in order to assess whether a positive pH test might predict response to proton pump inhibitor therapy in a subset of functional dyspepsia patients. PATIENTS: Forty Helicobacter pylori-negative functional dyspepsia patients (35 males and 5 females, mean age (+/-S.E.M.) of 54+/-2.4 years) with predominantly unspecified dyspepsia subtype and normal distal oesophageal biopsies. METHODS: All subjects were randomised in a double-blind fashion to either omeprazole 20 mg/day or placebo daily for four weeks after 24-h pH monitoring. RESULTS: Twenty-four-hour pH monitoring was abnormal in 9 of the 21 patients (43%) in the omeprazole group and 5/19 (26%) of the placebo group (p=NS). Patients who reported symptomatic improvement on the Gastrointestinal Symptom Rating Scale were no more likely to have abnormal scores on pH monitoring than patients who did not have symptomatic response. CONCLUSIONS: Although approximately one-third of functional dyspepsia patients will have abnormal profiles on 24-h ambulatory oesophageal pH monitoring, an abnormal score does not appear to predict response to proton pump inhibitor therapy in patients with unspecified functional dyspepsia.