Presenting features of newly diagnosed rheumatic heart disease patients in Mulago Hospital: a pilot study

Introduction

Rheumatic heart disease (RHD) continues to cause gross distortions of the heart and the associated complications of heart failure and thromboembolic phenomena in this age of numerous high-efficacy drugs and therapeutic interventions. Due to the lack of contemporary local data, there is no national strategy for the control and eradication of the disease in Uganda. This study aimed to describe the presenting clinical features of newly diagnosed patients with RHD, with particular reference to the frequency of serious complications (atrial fibrillation, systemic embolism, heart failure and pulmonary hypertension) in the study group.

Methods

One hundred and thirty consecutive patients who satisfied the inclusion criteria were recruited over a period of eight months from June 2011 to January 2012 at the Mulago Hospital, Uganda. Data on demographic characteristics, disease severity and presence of complications were collected by means of a standardised questionnaire.

Results

Seventy-one per cent of the patients were female with a median age of 33 years. The peak age of the study group was 20 to 39 years, with the commonest presenting symptoms being palpitations, fatigue, chest pain and dyspnoea. The majority of the patients presented with moderate-to-severe valvular disease. Pure mitral regurgitation was the commonest valvular disease (40.2%), followed by mitral regurgitation plus aortic regurgitation (29%). Mitral regurgitation plus aortic regurgitation plus mitral stenosis was found in 11% of patients. There was only one case involving the tricuspid valve. The pulmonary valves were not affected in all patients; 45.9% of patients presented in severe heart failure in NYHA class III/IV, 53.3% had pulmonary hypertension, 13.9% had atrial fibrillation and 8.2% had infective endocarditis. All patients presented with dilated atria (> 49 mm).

Conclusion

A significant proportion of RHD patients present to hospital with severe disease associated with severe complications of advanced heart failure, pulmonary hypertension, infective endocarditis and atrial fibrillation. There is a need to improve awareness of the disease among the population, and clinical suspicion in primary health workers, so that early referral to specialist management can be done before severe damage to the heart ensues.     

Patient expectations of fair complaint handling in hospitals: empirical data

Background  

A common finding in several studies is patients' dissatisfaction with complaint handling in health care. The reasons why are for the greater part unknown. The key to an answer may be found in a better understanding of patients' expectations. We investigated patients' expectations of complaint handling in hospitals.     

Phonological development of toddlers with unilateral cleft lip and palate who were treated with and without infant orthopedics: a randomized clinical trial.

OBJECTIVE: To investigate the phonological development of toddlers from 2 to 3 years of age with complete unilateral cleft lip and palate (UCLP) treated during the first year of life with and without infant orthopedics (IO). DESIGN: In a randomized clinical trial (Dutchcleft), two groups of children were followed up: one treated with IO (IO group) and another that did not receive IO (non-IO group). Phonological skills were analyzed at 2, 2.5, and 3 years of age using a system for assessing phonological development of Dutch children (Fonologische Analyse van het Nederlands: FAN). The analysis included number of acquired consonants, order of phonological development, use of phonological processes, and occurrence of nasal escape. PATIENTS: Criteria for inclusion were complete UCLP, no soft tissue bands, no other malformations, parents fluent in Dutch, birth weight of a minimum of 2500 g, and gestation time of a minimum of 38 weeks. INTERVENTIONS: IO treatment based on a modified Zurich approach was started within 2 weeks after birth and used until soft palate closure at 12 months of age. Children in the non-IO group visited the clinic for an extra check-up at 6 weeks as well as before and after lip repair and soft palate closure. All other interventions were the same across groups. RESULTS: Phonological development of most 2.5-year-old IO children was normal or delayed. Most children in the non-IO group followed an abnormal developmental pattern. At age 3, the children in the IO group had acquired more initial consonants. There were no group differences in the use of phonological processes or the occurrence of nasal escape. CONCLUSIONS: Children treated with IO during their first year of life followed a more normal path of phonological development between 2 and 3 years of age.     

Cognitive dysfunction is associated with poor diabetes control in older adults

OBJECTIVE: To evaluate the association between cognitive dysfunction and other barriers and glycemic control in older adults with diabetes. RESEARCH DESIGN AND METHODS: Patients over the age of 70 years presenting to a geriatric diabetes clinic were evaluated for barriers to successful diabetes management. Patients were screened for cognitive dysfunction with the Mini Mental State Examination (MMSE) and a clock-drawing test (CDT) scored by 1) a method validated by Mendez et al. and 2) a modified CDT (clock in a box [CIB]). Depression was evaluated with the Geriatric Depression Scale. Interview questionnaires surveyed activities of daily living (ADLs) and instrumental ADLs (IADLs), as well as other functional disabilities. RESULTS: Sixty patients (age 79 +/- 5 years, diabetes duration 14 +/- 13 years) were evaluated. Thirty-four percent of patients had low CIB (< or =5), and 38% of patients had low CDT (< or =13). Both CIB as well as CDT were inversely correlated with HbA(1c), suggesting that cognitive dysfunction is associated with poor glycemic control (r = -0.37, P < 0.004 and r = -0.38, P < 0.004, respectively). Thirty-three percent of patients had depressive symptoms with greater difficulty completing the tasks of the IADL survey (5.7 +/- 1.7 vs. 4.6 +/- 2.0; P < 0.03). These older adults with diabetes had a high incidence of functional disabilities, including hearing impairment (48%), vision impairment (53%), history of recent falls (33%), fear of falls (44%), and difficulty performing IADLs (39%). CONCLUSIONS: Older adults with diabetes have a high risk of undiagnosed cognitive dysfunction, depression, and functional disabilities. Cognitive dysfunction in this population is associated with poor diabetes control.     

Differential 2-D protein gel electrophoresis analysis of Legionella pneumophila wild type and Tat secretion mutants

The twin-arginine translocation (Tat) pathway is a secretory pathway for translocation of folded proteins with two arginines in their signal peptide across the cytoplasmic membrane. Recently, we showed the presence of the Tat secretion pathway in Legionella pneumophila Philadelphia-1 and its role in intracellular replication and biofilm formation. To analyse the importance of the Tat pathway in protein export and its role in L. pneumophila virulence, a comparative 2-D protein gel electrophoresis analysis was performed on supernatants of the wild type and two Tat secretion mutants in order to identify possible Tat substrates. Twenty proteins were identified as differential proteins, eight of which were present in a lower quantity in the supernatant of the tat mutants. Among these, one protein with a typical twin-arginine motif in its signal peptide was identified as the 3′,5′-cyclic nucleotide phosphodiesterase. Two other proteins that resulted as differential proteins from this study were flagellin and LvrE, which were studied in more detail and their Tat-dependence was further confirmed with specific antibodies. LvrE was shown to play a role in intracellular growth in differentiated U937 cells.     

Wachstum und Zellersatz in der Vitaminforschung

Ohne ZusammenfassungMit 19 Textabbildungen.     

Directing the use of DDR kinase inhibitors in cancer treatment

Introduction: Defects in the DNA damage response (DDR) drive the development of cancer by fostering DNA mutation but also provide cancer-specific vulnerabilities that can be exploited therapeutically. The recent approval of three different PARP inhibitors for the treatment of ovarian cancer provides the impetus for further developing targeted inhibitors of many of the kinases involved in the DDR, including inhibitors of ATR, ATM, CHEK1, CHEK2, DNAPK and WEE1.

Areas covered: We summarise the current stage of development of these novel DDR kinase inhibitors, and describe which predictive biomarkers might be exploited to direct their clinical use.

Expert opinion: Novel DDR inhibitors present promising candidates in cancer treatment and have the potential to elicit synthetic lethal effects. In order to fully exploit their potential and maximize their utility, identifying highly penetrant predictive biomarkers of single agent and combinatorial DDR inhibitor sensitivity are critical. Identifying the optimal drug combination regimens that could used with DDR inhibitors is also a key objective.