Medical education dilemma: How can we best accommodate basic sciences in a curriculum for 21st century medical students? 1.

Over the years, the medical curriculum has been changed to accommodate a variety of evolving disciplines and an exploding scientific knowledge of the basic sciences to prepare "a competent physician" of the 21st century. Therefore, we must be innovative in our approach of curricular development if we wish to continue to incorporate new basic sciences knowledge in the face of decreasing contact hours to satisfy the buzz word, "integration". Certainly, the challenges are phenomenal. The question how to best integrate basic sciences, is not easy to answer as the objectives of the courses and outcome vary from one medical school to another and the fact is, one size does not fit all. However, if we believe that basic sciences are the language of medicine and foundation of clinical knowledge, then we must resolve this ongoing dilemma by introducing basic sciences through a better alignment in a given curriculum. The purpose of this review is to evaluate different curricular models for their basic sciences content and address their strengths and weaknesses. In addition, we will introduce a spiral design to integrate basic sciences for senior students. Finally, we will provide some insight as to how learning and retention of basic science content can be sustained.

Investigation of an algorithm for anti HCV EIA reactivity in blood donor screening in Turkey in the absence of nucleic acid amplification screening.

PURPOSE: In this study we aimed to propose an algorithm for initial anti HCV EIA reactive blood donations in Turkey where nucleic acid amplification tests are not yet obligatory for donor screening. METHODS: A total of 416 anti HCV screening test reactive donor samples collected from 13 blood centers from three cities in Turkey were tested in duplicate by Ortho HCV Ab Version 3.0 and Radim HCV Ab. All the repeat reactive samples were tested by INNO-LIA HCV Ab 3.0 or Chiron RIBA HCV 3.0 and Abbott Real Time HCV. Intra-assay correlations were calculated with Pearson r test. ROC analysis was used to study the relationship between EIA tests and the confirmatory tests. RESULTS: The number of repeat reactive results with Ortho EIA were 221 (53.1%) whereas that of microEIA, 62 (14.9%). Confirmed positivity rate was 14.6% (33/226) by RIBA and 10.6% (24/226) by NAT. Reactive PCR results were predicted with 100% sensitivity and 95% specificity with S/CO levels of 8.1 with Ortho EIA and 3.4 with microEIA. CONCLUSIONS: Repeat reactivity rates declined with a second HCV antibody assay. Samples repeat reactive with one HCV antibody test and negative with the other were all NAT negative. All the NAT reactive samples were RIBA positive. None of the RIBA indeterminate or negative samples were NAT reactive. Considering the threshold values for EIA kits determined by ROC analysis NAT was decided to be performed for the samples above the threshold value and a validated supplemental HCV antibody test for the samples below.

Comparison of stored umbilical cord blood and adult donor blood: transfusion feasibility.

OBJECTIVE: This study aimed to compare the storage properties of red blood cell (RBC) concentrates of umbilical cordblood (UCB) and adult donor blood (ADB), and to evaluate the feasibility of UCB-RBC concentrate as an autologoussource for blood transfusion in very low birth weight (VLBW) preterm neonates. MATERIAL AND METHODS: In all, 30 newborn (10 preterm, 20 full term) UCB and 31 ADB units were collected.RBC concentrates were stored and compared with regard to pH, potassium (K(+)), 2,3-biphosphoglycerate (2-3-BPG),adenosine tri-phosphate (ATP), plasma Hb, and bacterial contamination on d 1, 21, and 35 of storage. RESULTS: The K(+) level increased with time and differed significantly between storage d 1 and 21, and between storaged 1 and 35 in both the UCB and ADB units. Initial and d 21 K(+) levels were higher in the UCB units than in the ADBunits. The 2,3-BPG level did not differ significantly between the UCB-PRC and ADB-PRC samples. After 35 d of storageboth UCB-PRC and ADB-PRC samples exhibited significant differences from the initial free Hb, intracellular ATP, andpH values. Significant differences in intracellular ATP and pH were also observed between the UCB-PRC and ADB-PRCsamples. CONCLUSION: The volume of harvested and prepared UCB-PRC can be used for some of the blood transfusions requiredduring the neonatal period and thus may decrease the number of allogeneic transfusions, especially in preterm newborns.The hematological and biochemical changes that occurred in UCB during storage were comparable with those observedin ADB, and do not pose a risk to the immature metabolism of neonates. UCB-RPC prepared and stored under standardconditions can be a safe alternative RBC source for transfusions in VLBW newborns.

The significance of repeat testing in Turkish blood donors screened with HBV, HCV and HIV immunoassays and the importance of S/CO ratios in the interpretation of HCV/HIV screening test results and as a determinant for further confirmatory testing.

The purpose of this study was to investigate the intra-assay correlations amongst initial reactive and repeat screening results used in enzyme immunoassays (EIAs) for hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV in blood donors. This study evaluated the value of using the power of the signal to cut-off (S/CO) ratio index for confirming anti-HCV/HIV reactive screening results, thereby touching upon the utility of S/CO indices in determining whether further confirmatory testing was necessary. Screening test results of the 72,695 blood donors were evaluated over a 1-year period. Correlation analysis among each initial test and retests was done by Pearson r test. Appropriate S/CO values to determine the need of the confirmation testing was investigated by ROC analyses. EIA intra-assay correlations were of statistical significance and were determined as follows: 0.948 for anti-HCV, 0.827 for anti-HIV and 0.948 for HBsAg. The threshold S/CO ratio values which predicted more than 95% of the confirmation test result were 3.8 for HCV and 5.6 for HIV. We were able to demonstrate a strong level of intra-assay correlation amongst EIAs, thereby eliminating the need for repetition of the screening test. Hence, we suggest that repeat screening should only be limited to HBV and HIV tests with low EIA S/CO ratios. Thus, using the power of the S/CO ratio in determining the need for HCV confirmation testing can be a cost-effective measure, especially if the S/CO value is >or=3.8.

Inhibitor screening for patients with hemophilia in Turkey.

Development of factor VIII inhibitors remains the most serious and life-threatening complication of hemophilia therapy. The aim of this study was to determine the prevalence of inhibitor development in Turkish patients with hemophilia. Totally 1226 patients were screened [HA: 1057, HB: 105, von Willebrand's disease (vWD): 64]. Ages ranged from 1 to 55 years (mean: 16.5 years). Sixty-two percent of patients (657/1057) were severe hemophilia. This study showed that inhibitor prevalence in Turkish hemophiliacs exposed to factor concentrates and fresh frozen plasma (FFP) is 11.2% for all HA and 15.8% for severe HA versus 1.9% for HB after eliminating transient inhibitors. Totally 122 patients were found inhibitor positive [high responder (HR) inhibitor= 60 and low responder (LR) inhibitor= 59 for HA/2 LR for HB/1 LR for vWD]. Thanks to this project, patients with inhibitor development can be treated with specific products such as recombinant factor VIIa or activated protrombin complex concentrates for their bleeding episodes or in their elective operations.

Granulocyte transfusions in children with chronic granulomatous disease and invasive aspergillosis.

The transfusion of granulocytes to restore host defenses in severely granulocytopenic patients or in patients with defective granulocyte functions has been studied for more than 60 years. However, inadequate dosage of cells and inconsistent efficacy has limited the usage of these transfusions. Recently, the use of mobilizing agents such as granulocyte colony stimulating factors and dexamethasone has renewed interest in these treatment modalities. The present study is conducted to determine an appropriate method of enriched granulocyte collection with Fresenius AS.TEC.204 cell separator (Fresenius, Bad Homburg, Germany) and to evaluate the preliminary clinical results of granulocyte transfusion therapy in patients with chronic granulomatous disease and invasive Aspergillosis in parallel with in vitro granulocyte function. Three patients who have been treated for chronic granulomatous disease and invasive Aspergillosis received a total of 20 granulocyte transfusions. To mobilize granulocytes, healthy donors were given 450 microg of granulocyte colony-stimulating factor (G-CSF) subcutaneously and 8 mg of dexamethasone orally approximately 12 h before collection. Five microg/kg/day of G-CSF was also subcutaneously administered prior to granulocyte transfusions. The first patient received 4; the second, 14 and the third, 2 transfusions. The granulocyte count given to these patients ranged between 0.4 and 3.0 x 10(9)/kg. Most transfusions were well tolerated. The nitroblue tetrazolium (NBT) tests that were done 16-24 h after the transfusion showed 14-46% dye reduction. Two of the three patients survived the infection. Granulocyte transfusions from G-CSF and dexamethasone stimulated donors could be a choice of treatment in chronic granulomatous disease patients, especially with disseminated invasive Aspergillosis.

HBV, HCV and HIV seroprevalence among blood donors in Istanbul, Turkey: how effective are the changes in the national blood transfusion policies?

The national blood transfusion policies have been changed significantly in recent years in Turkey. The purpose of this study was to determine the prevalence of HBV, HCV, and HIV in blood donors at the Red Crescent Center in Istanbul and to evaluate the effect of changes in the national blood transfusion policies on the prevalence of these infections. The screening results of 72695 blood donations at the Red Crescent Center in Istanbul between January and December 2007 were evaluated retrospectively. HBsAg, anti-HCV, and anti-HIV-1/2 were screened by microparticle enzyme immunoassay (MEIA) method. Samples found to be positive for anti-HIV 1/2 and anti-HCV were confirmed by Inno-Lia HCV Ab III and Inno-Lia HIV I/II Score, respectively. The seropositivity rates for HBsAg, anti-HCV, and anti-HIV-1/2 were determined as 1.76%, 0.07%, and 0.008%, respectively. Compared to the previously published data from Red Crescent Centers in Turkey, it was found that HBV and HCV seroprevalances decreased and HIV seroprevalance increased in recent years. In conclusion, we believe that the drop in HBV and HCV prevalence rates are likely multifactorial and may have resulted from more diligent donor questioning upon screening, a higher level of public awareness on viral hepatitis as well as the expansion of HBV vaccination coverage in Turkey. Another factor to contribute to the decreased prevalence of HCV stems from the use of more sensitive confirmation testing on all reactive results, thereby eliminating a fair amount of false positive cases. Despite similar transmission routes, the increase in HIV prevalence in contrast to HBV and HCV may be linked to the increase in AIDS cases in Turkey in recent years.

Platelet aggregation in term and preterm newborns.

The platelets of newborns have a hyporeactive period. This period, during which the platelet count is normal but their functions are deficient, is called transient platelet hyporeactivity of newborns. The platelet functions and their normalizing process of term and preterm neonates are investigated. Twenty term and 20 preterm (gestational age <37 weeks) newborns were enrolled in the study. Twenty-eight healthy children aged 2 months to 3 years old participated in the study as the control group. Healthy newborns were followed for 15 days after birth longitudinally in 3 periods: period 1 (0-4 days), period 2 (5-9 days), period 3 (10-15 days). Aggregation studies were performed from whole blood samples. Whole blood aggregation was measured by the impedance method. Transient hyporeactivity of platelets was found in term and preterm groups, and there was no difference between term and preterms. Platelets of newborns gained their normal functions at postnatal 10-14 days. The results show that hyporeactivity of platelets during the first 9 days of life is physiological and transient.

HBV, HCV and HIV seroprevalence among blood donors in Istanbul, Turkey: how effective are the changes in the national blood transfusion policies?

The national blood transfusion policies have been changed significantly in recent years in Turkey. The purpose of this study was to determine the prevalence of HBV, HCV, and HIV in blood donors at the Red Crescent Center in Istanbul and to evaluate the effect of changes in the national blood transfusion policies on the prevalence of these infections. The screening results of 72695 blood donations at the Red Crescent Center in Istanbul between January and December 2007 were evaluated retrospectively. HBsAg, anti-HCV, and anti-HIV-1/2 were screened by microparticle enzyme immunoassay (MEIA) method. Samples found to be positive for anti-HIV 1/2 and anti-HCV were confirmed by Inno-Lia HCV Ab III and Inno-Lia HIV I/II Score, respectively. The seropositivity rates for HBsAg, anti-HCV, and anti-HIV-1/2 were determined as 1.76 percent, 0.07 percent, and 0.008 percent, respectively. Compared to the previously published data from Red Crescent Centers in Turkey, it was found that HBV and HCV seroprevalances decreased and HIV seroprevalance increased in recent years. In conclusion, we believe that the drop in HBV and HCV prevalence rates are likely multifactorial and may have resulted from more diligent donor questioning upon screening, a higher level of public awareness on viral hepatitis as well as the expansion of HBV vaccination coverage in Turkey. Another factor to contribute to the decreased prevalence of HCV stems from the use of more sensitive confirmation testing on all reactive results, thereby eliminating a fair amount of false positive cases. Despite similar transmission routes, the increase in HIV prevalence in contrast to HBV and HCV may be linked to the increase in AIDS cases in Turkey in recent years.

Clinical Teaching and OSCE in Pediatrics.

Emphasis is being given to early contact by medical students with patients, and curricula are being designed to address this trend. Although teaching of clinical skills mostly depends on the traditional "apprenticeship" model, there is insufficient supervision of students while they examine the patients. This leads to the lack of acquisition of good clinical skills and some patient-student frustrations during examination by inexperienced students. The problem is greater in pediatric departments. One way to overcome this is to observe the students while they take a history and do a physical examination and to give them feedback. On the other hand, objective structured clinical examinations (OSCEs) should be used more in pediatric examinations to make use of the steering effect such examinations have on student achievement. However, OSCEs should not be the only student assessment tool, but should be complemented by other examination methods.

Factor V Leiden and prothrombin gene 20210A variant in neonatal thromboembolism and in healthy neonates and adults: a study in a single center.

This study was conducted to identify the prevalence of FV1691A and PT20210A mutations in neonates with symptomatic thromboembolism and in healthy neonates and adults. A review of 137 healthy neonates, 368 healthy adults, and 9 neonates with clinical thrombosis was done to investigate for hereditary prothrombotic mutations. For the neonates with thromboembolism, data were collected to reveal the underlying diagnosis, site of thrombosis, and associated risk factors. Investigations included screening for factor V 1691A and prothrombin 20210A. Seven of 9 neonates had one or more risk factors at the time of thromboembolism. Seventy percent (5/7) had underlying congenital thrombophilia (4/7 FV Leiden, 1/7 homozygote protein C deficiency). Among the healthy population, 11.9% of the neonates and 9% of the adults had FV1691A mutation, 4.8% of the neonates and 2.7% of the adults had PT 20210A mutation. Incidence of FV1691A mutation in the neonates with symptomatic thromboembolism was very high. The prevalence of both FV1691A and PT20210A mutations were remarkably higher than previously reported.

Molecular pathology of haemophilia B in Turkish patients: identification of a large deletion and 33 independent point mutations.

Heterogeneous mutations in the coagulation factor IX (FIX) gene result in a bleeding tendency known as haemophilia B. The haemophilia B mutation database has a total of 2353 patient entries, including 10 of the estimated 1000 Turkish patients. In this study, a more comprehensive analysis of the molecular pathology of haemophilia B in Turkey revealed one large deletion and 33 point mutations in the FIX gene of 34 unrelated patients. Haplotype analysis using six polymorphic sites showed that the mutations identified in a total of 45 patients occurred on 13 different haplotypes and that each mutation was family specific.

How we derived a core curriculum: from institutional to national--Ankara University experience.

As the first phase of a major curricular change in a large medical school the core curriculum had to be determined. The criteria for the inclusion of topics in the core curriculum were defined for both clinical and basic sciences. A large group of faculty members have worked in 11 sub-groups to determine the core knowledge, skills and attitudes for undergraduate medical students. During this work 608 clinical topics have been reviewed. Four-hundred and eighty five of them (79%) have been included in the core curriculum. Clinical and basic science knowledge, skills and attitudes relevant to these topics have been defined and classified. A total of 1610 cognitive, 428 psychomotor skills and 247 attitudes have been named. Thus the core curriculum defined is not just a set of diseases, conditions and symptoms but also includes the details of each and every topic. Starting from this point the medical school has participated actively in defining the national core curriculum, which has also been determined according to the same criteria.