Cryptococcal meningitis (C. neoformans var. gattii) leading to blindness in previously healthy melanesian adults in Papua New Guinea

Cryptococcal meningitis is a common cause of chronic meningitisin Papua New Guinea, affecting apparently immunocompetent people.The majority of infections are believed to be due to Cryptococcusneoformans var. gattii. We have reviewed the records of49 Melanesian adults who presented with proven cryptococcalmeningitis to the University teaching hospital in Port Moresby,and compare our findings with other published studies of cryptococcalmeningitis in the tropics and sub-tropics. None of the patientshad an obvious cause of immunosuppression. Visual disturbancesand fundoscopic changes of papilloedema or papillitis were particularlycommon. The in-hospital case fatality rate for patients treatedwith amphotericin B and flucytosine was 22.4%. Of the fullytreated patients, 31% became completely blind before being dischargedfrom hospital. Therapy directly aimed at reducing intracranialpressure may improve outcome.     

Serological distinction of integral plasma membrane proteins as a class of mycobacterial antigens and their relevance for human T cell activation

This study pertains to classification and antigenic analysis of mycobacterial plasma membrane proteins in relation to human T cell proliferative responses, using a ‘fast grower’ Mycobacterium fortuitum as model. Membrane vesicles, prepared by sonication and differential centrifugation, were subjected to biphasic Triton X-1 14 extraction for isolation of integral (detergent phase) and peripheral (aqueous phase) proteins. Neither protein pool showed any appreciable overlap serologically. SDS-PAGE showed five prominent bands in peripheral and three in the integral protein pool, whereas immunoblotting with rabbit antisera identified only two major antigens (60 and 67kD) in the former and five (24, 34, 42, 51 and 54kD) in the latter, ELISA with a panel of anti-mycobacterial MoAbs revealed that nine out of 12 previously known antigens were present in the peripheral protein pool. Only two of them (33 and 40 kD) were additionally detected amongst integral proteins. The membrane-associated immunosuppressive moiety lipoarabinomannan was semiquantitatively located in aqueous phase. In bulk T cell proliferation assays, seven out of 10 subjects belonging to a ‘responder’ background (BT-BB leprosy patients and healthy contacts) showed high responses for Myco. fortuitum antigens. Proliferative response with integral proteins was comparable to that with whole membrane, hut it was significantly higher (P < 0.0005) than t he response with peripheral proteins. The distinction and relevance of integral membrane proteins as a class of mycobacterial antigens make them worthy of consideration in a subunit vaccine design.     

The final outcome of indeterminate cytology of thyroid nodules in a District General Hospital

Background

Diagnostic thyroid lobectomy is performed to resolve the dilemma of indeterminate (Thy3) cytology of thyroid nodules. But on final histology most nodules are benign thereby subjecting this group of patients to surgery with its associated risks.

Aim

To determine the proportion of cancers in patients with indeterminate thyroid nodules.

Patients and methods

This is a retrospective observational study of 621 patients who underwent fine needle aspiration cytology (FNAC) of their thyroid nodules over a 60 month period in a district general hospital. Patient demographics, cytology and final histology results were extracted from the hospital database.

Results

On final analysis, 48 patients had an indeterminate cytology (7.7%) and 12 patients had cancer in this group (25%) following diagnostic lobectomy.

Conclusion

Till an alternative robust technology becomes widely available we need to continue to perform diagnostic lobectomy in patients with indeterminate cytology in view of the high incidence of thyroid cancer in this group of patients.     

An audit of consenting practices in a district general hospital. Can we improve?

Introduction

Informed consent, as the declaration of patients’ will, forms the basis of legality of medical procedures. A standard form based on the Department of Health model is widely used in the National Health Service (NHS). The aim of this audit process was to assess the current consent practice in comparison to the UK’s General Medical Council guidance and local policy and make any appropriate improvements.

Patients and methods

254 adult consent forms were reviewed during the patients’ admission. Data collected included legible documentation, grade of health professional completing the consent form, providing additional written information, use of abbreviations, securing the consent form in the medical records and, providing a copy to the patient. After initial assessment, interventions in an attempt to improve adherence to guidelines were introduced. A repeat audit of a further set of 110 notes was completed to assess the effectiveness of our interventions.

Results

Our baseline assessment of 254 consent forms comprised of 198 (78%) elective and 56 (22%) emergency procedures. 87 (34%) consent forms were secure in the medical records. Grade of health professional was recorded in 211 (83%). 191 (75%) forms were legible. 48 (19%) patients were given copy of the consent. Only 24 (9%) patients were given additional written information. Abbreviations were used in 68 (27%) forms. Only 12 (5%) of consent forms met all criteria simultaneously.Re-audit after intervention assessed 110 consent forms; 30 (27%) for elective and 80 (72%) for emergency procedures. 52 (47%) of consent forms were secure in medical records, grade of health professional was recorded in 94 (85%), 101 (75%) forms were legible, 42 (38%) patients received copy of consent and 41 (37%) of patients received additional written information.

Conclusion

Initially only 5% of consent forms completely met GMC guidelines. This demonstrates an alarmingly poor adherence to such guidance that plays a vital role in patient safety, patient ethics autonomy, not to mention potential medico-legal and clinical governance implications for surgical practice.Our intervention has improved the quality of consenting within our hospital according to these guidelines. With these interventions set to continue and further develop, we expect that the quality of the consenting process will continue to provide patients with all that it is designed to.     

Abrus agglutinin suppresses human hepatocellular carcinoma in vitro and in vivo by inducing caspase- mediated cell death

Aim： Abrus agglutinin （AGG） from the seeds of Indian medicinal plant Abrus precatorius belongs to the class II ribosome inactivating protein family. In this study we investigated the anticancer effects of AGG against human hepatocellular carcinoma in vitro and in vivo.
Methods： Cell proliferation, DNA fragmentation, Annexin V binding, immunocytofluorescence, Western blotting, caspase activity assays and luciferase assays were performed to evaluate AGG in human liver cancer cells HepG2. Immunohistochemical staining and TUNEL expression were studied in tumor samples of HepG2-xenografted nude mice.
Results： AGG induced apoptosis in HepG2 cells in a dose- and time-dependent manner. AGG-treated HepG2 cells demonstrated an increase in caspase 3/7, 8 and 9 activities and a sharp decrease in the Bcl-2/Bax ratio, indicating activation of a caspase cascade. Co-treatment of HepG2 cells with AGG and a caspase inhibitor or treatment of AGG in Bax knockout HepG2 cells decreased the caspase 3/7 activity in comparison to HepG2 cells exposed only to AGG. Moreover, AGG decreased the expression of Hsp90 and suppressed Akt phosphorylation and NF-κB expression in HepG2 cells. Finally, AGG treatment significantly reduced tumor growth in nude mice bearing HepG2 xenografts, increased TUNEL expression and decreased CD-31 and Ki-67 expression compared to levels observed in the untreated control mice bearing HepG2 cells.
Conclusion： AGG inhibits the growth and progression of HepG2 cells by inducing caspase-mediated cell death. The agglutinin could be an alternative natural remedy for the treatment of human hepatocellular carcinomas.     

Maternal and neonatal outcomes following diabetes in pregnancy in Far North Queensland, Australia

Background: Diabetes in pregnancy (DIP) is increasing and is associated with a number of adverse consequences for both the mother and the child.
Aims: To compare local maternal and neonatal outcomes with state and national data.
Methods: Chart audit of all DIP delivered during 2004 at a regional teaching hospital and compare outcomes with national benchmark, Queensland and national Indigenous data.
Results: The local DIP frequency was 6.7%. The local compared to benchmark and state data demonstrated a higher frequency of Indigenous mothers (43.6% vs 6.8% vs 5.5%), caesarean sections (50.7% vs 26% vs 32.0%), hypoglycaemia (40.7% vs 19.5% vs 2.7%) and respiratory distress (16.6% vs 4.5% vs 2.3%) in infants, fewer normal birthweights (64.8% vs 82.6% vs 80.4%) and full-term deliveries. More local mothers compared to benchmark had type 2 diabetes mellitus (T2DM) (15.4% vs 8.7%) but fewer used insulin (31.0% vs 46.6%); compared to state data, fewer women had gestational diabetes (79.5% vs 91.2%), however, insulin use was higher (22.8%). Furthermore, Aborigines had fewer pregnancies compared to Torres Strait Islanders (3.0 vs 5.0) and less insulin use (21.9% vs 59.3%) ( P  = 0.008–0.024). In contrast, non-Indigenous versus Indigenous women showed fewer pregnancies, less T2DM (7.8% vs 23.7%), better glycaemic control, longer babies, more full-term deliveries and less severe neonatal hypoglycaemia. Comparing local and national Indigenous data, local showed poorer outcomes, however, only 11.8% had diabetes or hypertension nationally.
Conclusion: The local cohort had poorer outcomes probably reflecting a more disadvantaged. Few differences were found between local Indigenous groups.     

Steady-State Spatial Patterns in a Cell-Chemotaxis Model

We investigate a simple cell-chemotaxis model for the generationof spatial patterns in cell aggregations. For simple boundary-valueproblems, we analyse the local and global bifurcation of spatiallyheterogeneous patterns away from the uniform equilibria as thetotal number of cells is varied. We also discuss the existenceof periodic spatially structured solutions for the cells andchemoattractant in the infinite domain.     

Outcomes in Patients Requiring Cardioversion Following Catheter Ablation of Atrial Fibrillation

Outcomes of Cardioversion Post AF Ablation.   Introduction: Early recurrence of atrial tachyarrhythmias is commonly noted after catheter ablation of atrial fibrillation (AF). The long-term outcomes of patients who require cardioversion for persistent AF after AF ablation is not known. This study reports the outcomes of patients who underwent cardioversion for persistent AF or atrial flutter following an AF ablation procedure.
Methods: The patient population comprised 55 patients (mean age 58 ± 10 years, 35% paroxysmal) who underwent catheter ablation of AF and subsequently required electrical cardioversion for persistent AF (45 patients) or atrial flutter (10 patients). Cardioversion was defined as early (within 90 days of the ablation procedure) or late (between 90 and 180 days following ablation).
Results: The mean follow-up duration was 15 ± 8 months. Forty-six of the 55 patients (84%) patients experienced recurrence during follow-up. The average time to recurrence after cardioversion was 37 days. Of the 55 patients, 8 (15%) patients had a complete success, 11 (20%) patients had a partial success and 36 patients (65%) had a failed outcome. Seven of the 43 patients (16%) who underwent early cardioversion had a complete success as opposed to one of 12 patients (8%) who underwent late cardioversion (P = 0.49).
Conclusions: This study shows that >80% of patients who undergo cardioversion for persistent AF or atrial flutter after AF ablation have recurrence. The timing of cardioversion did not affect the outcome. These findings allow clinicians to provide realistic expectations to patients regarding the long-term outcome and/or requirement for a second ablation procedure. (J Cardiovasc Electrophysiol, Vol. 21, pp. 27–32, January 2010)     

A Prospective Study Evaluating the Role of Obesity and Obstructive Sleep Apnea for Outcomes After Catheter Ablation of Atrial Fibrillation

Effect of Obesity and OSA on Outcomes Post AF Ablation . Background: Obesity and obstructive sleep apnea (OSA) have a strong association with atrial fibrillation (AF). The purpose of this study was to prospectively determine the effects of obesity, assessed by the body mass index (BMI) and OSA on the efficacy of catheter ablation of AF. Methods: The patient population consisted of 109 patients (mean age: 60 ± 10 years, 79% male, 67% paroxysmal, mean BMI 28 ± 5 kg/m²) who underwent catheter ablation of AF. Based on BMI, patients were classified as normal (<25 kg/m²), overweight (≥25 and <30 kg/m²), or obese (≥30 kg/m²). OSA was assessed by the Berlin questionnaire. Clinical success was defined as at least 90% reduction in AF burden after 3‐month blanking period. Mean duration of follow‐up was 11 ± 4 months. Results: Of the 75 patients with clinical success, 25 (33%) had normal BMI, 29 (39%) were overweight, and 21 (28%) were obese. Among the 34 patients with failed outcome, 5 (15%) had normal BMI, 14 (41%) were overweight, and 15 (44%) were obese (P = 0.04). Twenty‐eight of the 48 patients with OSA (58%) had clinical success as opposed to 47 of the 61 patients (77%) without OSA (P = 0.036). On multivariate analysis, only BMI emerged as an independent predictor of procedural failure ((OR 1.11, CI: 1.00–1.21, P = 0.03). Conclusions: The results of this prospective study show that obesity, a modifiable risk factor, is an independent predictor of procedural failure after catheter ablation of AF. Whether treating obesity may improve the results of catheter ablation of AF warrants further investigation. (J Cardiovasc Electrophysiol, Vol. 21, pp. 521‐525, May 2010)