Investing in scholarship for health professions education: Learning from the past to move into the future.

There have been recent discourses of what scholarship means for health professions education (HPE) and how it may need a rethink during the pandemic. One key take home message from these discourses is the role of institutions in nurturing and investing in scholarship. Given the current challenges faced by both higher education and healthcare, there is a risk that activities and resources for scholarship in HPE may be neglected. How do institutions make a case for continuous investment in HPE scholarship? Despite being a relatively new and small private university with no public funding, IMU has made fairly significant progress in delivering a unique model of HPE programmes with HPE scholarly output. This commentary discusses the importance of investing in scholarship for HPE with the International Medical University (IMU) in Kuala Lumpur, Malaysia as a case study. Examples of institutional initiatives that support and enhance scholarship are presented based on the recent AMEE guide (142) on redefining scholarship.

Clinical impact of ABCC1 and ABCC2 genotypes and haplotypes in mediating imatinib resistance among chronic myeloid leukaemia patients.

WHAT IS KNOWN AND OBJECTIVE: The introduction and success of imatinib mesylate (IM) has brought about a paradigm shift in chronic myeloid leukaemia (CML) treatment. However, despite the high efficacy of IM, clinical resistance develops due to a heterogeneous array of mechanisms. Pharmacogenetic variability as a result of genetic polymorphisms could be one of the most important factors influencing resistance to IM. The aim of this study was to investigate the association between genetic variations in drug efflux transporter ABCC1 (MRP1) and ABCC2 (MRP2) genes and response to IM in patients with CML. METHODS: We genotyped 215 Malaysian patients with CML (comprising of two groups with 108 IM resistant and 107 IM responsive) for polymorphisms of ABCC1 (2012G>T and 2168G>A) and ABCC2 (-24C>T, 1249G>A and 3972C>T) genes. Genotype, allele and haplotype frequencies were compared between two groups of patients. Patients with CML were further stratified according to their clinical response to IM into those having cytogenetics and molecular responses, and the associations with genotypes were evaluated. RESULTS AND DISCUSSION: We observed no significant differences in the distribution of any of the tested genotypes between the investigated groups. However, on evaluating the risk association, ABCC2 T₋24 G1249 T3972 haplotype was found to be associated with IM resistance (P = 0·046). These results suggest that haplotype variants -24T and 3972T might be associated with lower expression of ABCC2 protein and reduced transport activity and hence might be contributing to development of IM resistance. WHAT IS NEW AND CONCLUSION: Our results suggest the ABCC2 T₋24 G1249 T3972 haplotype was associated with imatinib resistance. However, the evidence is as yet insufficient to establish this haplotype as a predictive biomarker for response to the drug.

Polymorphism of ITPA 94C>A and risk of adverse effects among patients with acute lymphoblastic leukaemia treated with 6-mercaptopurine.

WHAT IS KNOWN AND OBJECTIVE: Genetic polymorphisms of thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphohydrolase (ITPA 94C>A) contribute to variable responses, including fatal adverse effects, among subjects treated with 6-mercaptopurine (6-MP). Our objectives were to investigate the distribution of specific TPMT and ITPA genotypes in healthy subjects and patients with acute lymphoblastic leukaemia (ALL) from the three main ethnic groups (Malays, Chinese and Indians) in Malaysia and the association of the polymorphisms with adverse effects of 6-MP. METHODS: Patients with ALL and healthy controls were recruited and genotyped for genetic variants of TPMT and ITPA 94C>A. The relationship between genotypes and clinical outcomes was investigated. RESULTS AND DISCUSSION: Acute lymphoblastic leukaemia patients with allele ITPA 94A were more likely to develop fever and liver toxicity with 6-MP. The prevalence of TPMT variants was low and this makes it unlikely that testing for them would be useful in our populations. Only patients heterozygous for TPMT*3C were detected. WHAT IS NEW AND CONCLUSION: Our results suggest that ITPA 94C>A testing, but not TPMT testing, may help in minimizing the adverse effects of 6-MP in Malaysian patients. However, whether this is true in clinical practice requires a larger study and formal randomized controlled evaluation.

Management of biliary ascariasis in children living in an endemic area.

BACKGROUND: One quarter of the world's population is known to be infected with ascariasis. It is endemic in various parts of the Indian subcontinent with a high incidence in the Kashmir valley. Although intestinal obstruction is the commonest complication of ascariasis in children, biliary ascariasis remains the second most common complication. We aimed to study the various types of clinical presentations, complications and different diagnostic tools and to assess various options for the management of biliary ascariasis. MATERIALS AND METHODS: Sixty-one cases of ultrasound documented hepatobiliary ascariasis were studied prospectively over a period of 3 years from Jan 2003 to Dec 2005 at the Sheri-Kashmir Institute of Medical Sciences in Srinagar, Kashmir. All patients were children aged between 3 and 14 years. All patients were admitted to hospital and put on intravenous fluids, nothing per os until patients were symptom-free, broadspectrum antibiotics and antispasmodics. All patients received antihelminthics in the form of albendazole 400 mg as soon as patients could accept oral medication. Conservative management was continued until the patients were symptom-free. Endoscopic extraction was deferred until 3 weeks later except in patients with pyogenic cholangitis where urgent endoscopic intervention was carried out. Surgical intervention was carried out if both conservative management and endoscopic extraction failed or ERCP could not be performed for technical reasons or complications developed. RESULTS: The most common presentation was upper abdominal pain in 36 (59%) patients followed by vomiting of worms in 20 (33.3%) cases. Complications included cholangitis in 8 (13.1%), obstructive jaundice in 7 (11.4%), acute pancreatitis in 1 (1.6%) and hepatic abscess in 1 (1.6%) patient. Spontaneous passage of worms from the biliary ducts was observed in 44 (72.1%) patients. ERCP was successful in 8 (13.1%) patients, and 9 (14.7%) patients needed surgical intervention. CONCLUSION: In endemic countries, ascariasis should be suspected in patients with biliary disease. Most patients respond to conservative management although a few may need surgical intervention. Although this disease is prevalent in developing countries, because of increased travel and migration, clinicians elsewhere should be aware of the problems associated with ascariasis.

Role of short chain fatty acids in mesenteric ischemia reperfusion injury in rats.

AIM: The aim of this study was to evaluate the role of short chain fatty acid administration in mesenteric ischemia reperfusion in rats. METHODS: Sixteen 60-day-old male Wistar rats were divided into two groups of eight each. In group I (n=8) normal saline (10 ml/kg) was injected into the ileal lumen. Ischemia reperfusion was achieved by clamping the superior mesenteric artery (SMA) for 30 min and then releasing it for another 30 min. The ileum was harvested for histopathological examination. In group II (n=8) a mixture of short chain fatty acids (10 ml/kg) was injected into the ileal lumen. Ischemia reperfusion was achieved in a similar fashion and the ileum harvested for histopathological examination. Injury was graded according to Chiu's score. RESULTS: The ileum in rats from group II showed a lower injury score (0.013+/-0.354) compared to ileum from rats in group I (4.631+/-0.521), and this difference was significant (p<0.001). CONCLUSION: Short chain fatty acids significantly decreased the degree of reperfusion injury in the gut in a rat model of mesenteric ischemia reperfusion.

Development of a combined pyro- and hydro-metallurgical route to treat spent zinc-carbon batteries.

The potential of solvent extraction using Cynanex272 for the recovery of zinc from spent zinc carbon batteries after a prior leaching in hydrochloric acid has been investigated. The elemental analysis of the spent material was carried out by ICP-MS. The major metallic elements are: ZnO (41.30%), Fe(2)O(3) (4.38%), MnO(2) (2.69%), Al(2)O(3) (1.01%), CaO (0.36%) and PbO (0.11%). The quantitative leaching by hydrochloric acid showed that the dissolution rates are significantly influenced by temperature and concentration of the acid solutions. The experimental data for the dissolution rates have been analyzed and were found to follow the shrinking core model for mixed control reaction with surface chemical reaction as the rate-determining step. About 90.3% dissolution was achieved with 4M HCl solution at 80 degrees C with 0.050-0.063 mm particle size within 120 min at 360 rpm. Activation energy value of 22.78 kJ/mol and a reaction order of 0.74 with respect to H(+) ion concentration were obtained for the dissolution process. An extraction yield of 94.23% zinc by 0.032M Cyanex272 in kerosene was obtained from initial 10 g/L spent battery leach liquor at 25+/-2 degrees C and at optimal stirring time of 25 min. Iron has been effectively separated by precipitation prior to extraction using ammoniacal solution at pH 3.5, while lead and other trace elements were firstly separated from Zn and Fe by cementation prior to iron removal and zinc extraction. Finally, the stripping study showed that 0.1M HCl led to the stripping of about 95% of zinc from the organic phase.

Assessment of knowledge, attitude and exposure to oncology and palliative care in undergraduate medical students.

We conducted a questionnaire survey among 261 year-4 and year-5 medical students containing 27 questions related to cancer, radiotherapy, general oncology and palliative care to assess their knowledge, understanding, and exposure to oncology and palliative care in our medical school. Out of 261 students, 139 students returned their questionnaire for analysis. Twenty nine percent (29%) of the students had rarely visited the Radiotherapy and Oncology unit. There were profound deficiencies in the basic knowledge of cancer (46%), principles of radiotherapy treatment (59%), palliative care (64%), and cancer prevention (48%). They reported no specific teaching about early detection of common malignancies and cancer prevention. The main input of instruction about cancer came from surgery (46%) and pathology (28%) teachings. This study revealed that there is deficiency in cancer education in the undergraduate teaching program in our institution.

Vaccination of BALB/c mice with Leishmania major amastigote-specific cysteine proteinase.

Cellular immune mechanisms resulting in interferon-gamma (IFN-gamma) production are essential for protection against cutaneous leishmaniasis. Antigens of the intracellular amastigote form of the parasite, found in mammalian hosts, are likely to be good candidates for the induction of T cell response and protection from development of leishmaniasis. We purified a stage-specific antigen from amastigote soluble antigen (A-SLA) of Leishmania major by immunoaffinity chromatography. The purified protein was characterized as a cysteine proteinase with enzymatic activity which is inhibited by E-64, and it was named the amastigote cysteine proteinase (ACP). BALB/c mice were immunized by two intraperitoneal injections, at a month interval, of 5 microg of ACP or A-SLA in Freund's complete adjuvant (FCA). Animals were challenged 4 weeks later with 106 L. major promastigotes and examined 4 months after the last injection. The immunized animals developed significantly smaller or no lesions compared with controls. Spleen cells from immunized mice showed a significant proliferative response and produced a high level of IFN-gamma in response to ACP, suggesting the induction of Th1 cells after immunization. These results make 24-kD ACP a possible component for an eventual cocktail vaccine against L. major infection.

Adult idiopathic thrombocytopenic purpura without the option of splenectomy.

In this part of Malaysia, consent of splenectomy is virtually unobtainable, so we studied the outcome of ITP without this treatment option. Thirty-two adult patients were seen, but 7 defaulted before therapy evaluation. Of the remaining 25, 17 achieved a complete remission with prednisolone, but in only 8 was this prolonged. Twelve patients, who failed to respond to prednisolone or who required > 15 mg/day as maintenance, were offered splenectomy, but all fused. Of these 12: one has died from an intracranial haemorrhage; three others have defaulted while on no treatment with platelet counts of < 16 x 10(9)/1; one has had a baby who died from intracranial bleeding. The other seven patients have platelet counts ranging from 4 - 202 x 10(9)/1 with moderate bleeding on doses of prednisolone of 0-60 mg/day: long-term corticosteroid side-effect are evident in all but one of them. This study demonstrates that ITP patients who refuse splenectomy have a high morbidity.

Undifferentiated carcinoma of the sinuses and cranial basis successfully treated with radiochemotherapy. A case report.

The frustration and disappointment in managing advanced cancers of the nose and paranasal sinuses are well known. We report a case of a successful treatment of such a tumour in a 37-year-old soldier, using a combination of therapy including surgery, chemotherapy and radiation. Each mode of treatment is discussed.

Indium 111 leucocyte scintigraphy in abdominal sepsis. Do the results affect management?

We have studied the clinical utility of indium 111 autologous leucocyte scintigraphy retrospectively in 45 patients presenting with suspected intra-abdominal sepsis. The sensitivity was 95% (21/22) and the specificity was 91% (21/23). Some 34 of the studies (17 positive and 17 negative) were considered helpful in furthering patient management (76%) and 8, unhelpful (18%). In 3, the study results were misleading and led to inappropriate treatment. Indium 111 scintigraphy, whether positive or negative, provides information in patients with suspected intra-abdominal sepsis upon which therapeutic decisions can be based.

Hypocalcaemia in autoimmune haemolytic anaemia and pernicious anaemia.

A 71 year old woman presented with hypocalcaemia in association with autoimmune haemolytic anaemia and pernicious anaemia. The hypocalcaemia resolved only when the haemolytic anaemia and pernicious anaemia were successfully treated. The possible pathogenic mechanisms are discussed.