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.     

Ventricular Tachycardia/Ventricular Fibrillation Ablation in the Setting of Ischemic Heart Disease

Recurrent ventricular tachycardia (VT) in the setting of coronary artery disease is frequently a life-threatening electrophysiologic emergency. Even in patients with an implantable defibrillator, recurrent VT is frequently accompanied by repeated and disabling shock therapy. Catheter ablative therapy offers the ability to provide immediate control of recurrent VT. Long-term elimination of VT should be anticipated in most patients. This article reviews the strategies, tools, techniques, and expected outcome for catheter ablation of stable and unstable ventricular arrhythmias in the setting ischemic heart disease.     

Electrophysiologic Spectrum of Atrioventricular Nodal Behavior in Patients with Atrioventricular Nodal Reentrant Tachycardia Undergoing Selective Fast or Slow Pathway Ablation

AV Nodal Behavior After Ablation. Introduction; The objective of this report is to delineate the atrioventricular (AV) nodal electrophysiologic behavior in patients undergoing fast or slow pathway ablation for control of their AV nodal reentrant tachycardia (AVNRT).
Methods and Results: One hundred sixteen consecutive patients with symptomatic AVNRT were included. Twenty-two patients underwent fast pathway ablation with complete abolition of AVNRT in all and development of complete AV block in five patients. Of 17 patients with intact AV conduction postablation, 12 had demonstrated antegrade dual pathway physiology during baseline study, which was maintained in three and lost in nine patients postablation. Two patients with successful fast pathway ablation developed uncommon AVNRT necessitating a slow pathway ablation. Twenty-one patients demonstrated both common and uncommon forms of AV nodal reentry during baseline study. The earliest site of atrial activation was close to the His-bundle recording site (anterior interatrial septum) during common variety and the coronary sinus ostium (posterior interatrial septum) during the uncommon AV nodal reentry in all 21 patients. Ninety-six patients underwent successful slow pathway ablation. Among these, the antegrade dual pathway physiology demonstrable during baseline study (60 patients) was maintained in 25 and lost in 35 patients postablation.
Conclusion: These data suggest that: (1) dual pathway physiology may persist after successful ablation, which might be a reflection of multiple reentrant pathways in patients with AVNRT: and (2) the retrograde pathways during common and uncommon AVNRT have anatomically separate atrial breakthroughs. These findings have important electrophysiologic implications regarding the prevailing concept of the AV nodal physiology in patients with AVNRT.     

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.