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Biomedical subjects

Iskender Sayek

Publications and source records attributed to Iskender Sayek.

At least 19 recordsLinked to original sources

Interleukin-10 gene transfer: prevention of multiple organ injury in a murine cecal ligation and puncture model of sepsis.

INTRODUCTION: The aim of this study was to determine the effect of immunoregulatory cytokine interleukin-10 (IL-10) gene therapy on multiple organ injury (MOI) induced by a cecal ligation and puncture (CLP) model of sepsis in mice. METHODS: Male Balb/c mice subjected to CLP were treated with either an hIL-10-carrying vector or an empty control vector. We assessed the degree of lung, liver, and kidney tissue destruction biochemically by measuring myeloperoxidase (MPO) and malondialdehyde (MDA) activity. Histologic assessments were based on neutrophil infiltration in lung and liver tissue. IL-10 protein expression was examined immunohistochemically, and ultrastructural changes in the liver were studied by transmission electron microscopy. We analyzed the expression of tumor necrosis factor-alpha (TNFalpha) mRNA by reverse transcription polymerase chain reaction 3, 8, and 24 hours after CLP in all organs. RESULTS: Organ damage was significantly reduced by hIL-10 gene transfer, which was associated at the tissue level with reduced MPO activity in the liver, lung, and kidney and decreased leukocyte sequestration and MDA formation in the lung. The liver MDA was not significantly higher in the hIL-10 gene therapy group than in the controls and seemed not to be affected by hIL-10 gene transfer. The reduced portal tract neutrophilic infiltration and preserved ultrastructure of the hepatocytes also showed that tissue function was not impaired. The lung and kidney TNFalpha mRNA expression was suppressed markedly in the hIL-10 gene therapy group, but liver TNFalpha mRNA expression varied over time. CONCLUSIONS: These findings showed that IL-10 gene therapy significantly attenuated sepsis-induced MOI.

Animals↗

Re-evaluation of axillary skip metastases in the era of sentinel lymph node biopsy in breast cancer.

PURPOSE: To investigate whether skip axillary metastases are really skip metastases or a continuation of level I micrometastases in invasive breast cancer, and to determine whether there are any factors predisposing to skip metastases. METHODS: We reviewed 568 consecutive patients with breast cancer who underwent complete axillary lymph node dissections (ALND) between January 1998 and December 2004. For patients with skip axillary lymph node metastases, resectioning and immunohistochemical staining of the remaining part of paraffin blocks from level I lymph nodes were done to determine whether there were any micrometastases in this group of lymph nodes. RESULTS: Skip axillary metastases were found in 27 (10%) of 268 patients with axillary lymph node metastases. Re-evaluation of the level I lymph nodes, both with thin sectioning and immunohistochemical staining, in the patients with axillary skip metastases revealed no micrometastases. No significant correlation was found between the demographic and histopathological variables of the patients with skip metastases and those with regular axillary metastases. CONCLUSIONS: These results suggest that skip axillary metastases are actual skip metastases, not a continuation of undetected level I micrometastases. Moreover, none of the clinical and histopathological measures of primary tumors are predictors of the presence of skip metastases.

Adult↗

In vivo characterisation of parathyroid lesions by use of gamma probe: comparison with ex vivo count method and frozen section results.

OBJECTIVE: In this study we hypothesized that if timing of gamma probe-guided parathyroidectomy were individualized according to an optimal-time-to-surgery technique, in vivo characterization of parathyroid lesions would be possible. We compared our findings with an ex vivo counting method ("20% rule") and frozen section results. STUDY DESIGN AND SETTINGS: Thirty-five patients who were referred for surgical treatment of hyperparathyroidism were studied. Maximum parathyroid to thyroid sestamibi uptake ratio (UR(max)) was measured by use of preoperative dynamic scintigraphy. The interval between sestamibi injection and UR(max) was defined as the optimal time to surgery. On the day of surgery, the patients received the same dose of sestamibi and were taken to the operating room at UR(max) as determined by preoperative scintigraphy. Intraoperative in vivo gamma probe counts from parathyroid lesions were compared with in vivo contralateral background thyroid counts (in vivo/Bkg) and to ex vivo parathyroid counts relative to postexcision background of the adjacent normal tissue (ex vivo/Bkg). RESULTS: A total of 70 excised lesions were evaluated. In vivo/Bkg counts obtained from parathyroid adenoma were significantly different from parathyroid hyperplasia (z = -3.093, P = 0.002) and other lesions (z = -3.958, P = 0.0001). By receiver operating characteristic curve (ROC) analysis, we found the cutoff value for the in vivo/Bkg counts ratio to be 103% to differentiate parathyroid adenoma from hyperplasia with a sensitivity, specificity, and accuracy of 82.5, 65, and 74.4%, respectively. On the other hand, sensitivity, specificity, and accuracy of the ex vivo/Bkg method to differentiate parathyroid adenoma from hyperplasia with a cutoff value of 34.7 was found to be 70.8%, 60%, and 65.9%, respectively. The difference between the accuracy of these 2 tests was not significant statistically (P = 0.137). Sensitivity of frozen section to differentiate parathyroid adenoma and hyperplasia was 76.2% and 33.3%, respectively. CONCLUSIONS: Patient-specific optimal protocol for timing of sestamibi injection together with in vivo/Bkg method is a useful alternative method in guiding the surgeon to differentiate parathyroid adenoma from parathyroid hyperplasia and other tissues and may help surgeons' decisions during the operation. Combined use of in vivo/Bkg and ex vivo/Bkg methods may give more accurate results than frozen section.

Adenoma↗

Developing and evaluating professionalism.

Professional behaviour, being one of the domains of professionalism, is an area of medical education that has long been of concern to medical educators. At Hacettepe University, our main goal is to have students become conscious of professional identity, values, responsibilities and the physician-patient relationship. We welcome our new students with an opening ceremony on their first day and two months later, the students start the course called "Health-Illness Concepts and Medical Professional Identity". Students are expected to discuss the subjects given to them as scenarios or arguments. The aim of our study is to determine whether the course leads to a positive change in students' attitudes, indicating the attainment of those attributes that reflect professionalism. On the first and the last days of the course, a questionnaire was delivered to the students. Any positive change in preferences between the two questionnaires is identified as an achievement of that attribute. As a result we found that in all of the seven attributes there were positive changes in the students' attitudes. Positive changes varied from 48% to 84% and all were statistically significant. Using more interactive techniques helped the students to make larger percentage changes in their awareness of these professional attributes.

Adult↗

Training of 'first-aid' trainers: a medical school example in Turkey.

OBJECTIVE: A student-oriented basic life support and first-aid training is practical to enlarge the number of qualified people in the field. In this study, we aimed to describe and discuss the training process of a group of medical students at Hacettepe University, School of Medicine and their assessment as basic life support and first-aid trainers. METHODS: A '6-hour' 'Training the Trainers' course was conducted and participants' demonstration and coaching skills were evaluated by using a 3-point scale (1 - needs improvement; 2 - competently performed; 3 - proficiently performed). In total, 31 students out of 45 volunteers were certified as trainers. RESULTS: All of the students proficiently performed 'explain the aim of the demonstration', 'motivate participants to use checklists', and 'motivate the participants to ask questions' for demonstraton skills. Similarly, they all got the maximum grade for 'answer the questions of the participant', 'discuss the coach role of the participant', 'apply the skills', and 'follow up with the participant by using the checklist' as steps of coaching skills. None of the skills within the checklists needed improvement for any of the candidates. CONCLUSION: Although there are limitations, we hope that our experience of the Training the Trainers course will be useful for readers to highlight the importance of skill-based peer education on a very important public health concern, especially for the developing countries.

Curriculum↗

Liposome-mediated intraperitoneal interleukin 10 gene transfer increases survival in cecal litigation and puncture model of sepsis.

Interleukin 10 (IL-10) has been considered to alleviate the inflammatory cytokine response in various models of sepsis. Although being regarded as a key immunomodulator molecule to be beneficial for the treatment of sepsis, recombinant IL-10 treatment is limited by efficacy and tolerability. We tested a novel approach and conducted i.p. liposomal IL-10 gene transfer 24 h before the cecal ligation and puncture in mice and observed 75% mortality at the end of the 7th day. The mortality was 100% in the group where the gene transfer was not performed. The transgene expression is observed mainly in the endothelium in all vital organs. The results demonstrate the advantageous role of de novo IL-10 synthesis in early stages of sepsis and suggest the beneficial impact of gene transfer approach to recombinant protein infusions.

Animals↗

The first medical humanities programme in Turkey.

THE MEDICAL HUMANITIES: The arts and humanities have been considered a recreational activity related to the interests and talents of the doctor, rather than to their practice of medicine. GOOD MEDICAL PRACTICE COURSE: At Hacettepe University, the 'good medical practice course' was added to the curriculum in September 2004. The goals of this course are to help the students achieve the skills and attitudes of a good doctor and to become competent in caring for and communicating with patients. IMPLEMENTATION: As a part of the programme, in the first 3 years students prepared 526 projects concerned with medical humanities in the broad areas of 'medicine and art', 'medicine and history' and 'man and medicine'. They presented 72 of the projects as short communications at the Medical Humanities Congress and the remaining projects as posters. Each project was also to be prepared as a portfolio. PROGRAMME EVALUATION: At the end of the programme, a questionnaire was given to both the students and the tutors to evaluate the course. The part of the programme rated most difficult was the medical humanities section, according to 67.1% of the students. They commented that it took a great deal of time to research and prepare the projects. PROPOSED CHANGES: The new concept and the extra workload, in addition to new medical knowledge, confused all the students. We have made some changes to the programme and have decided to develop a number of new activities. CONCLUSION: 'Medical humanities' is a new concept for almost all the students and the faculty; it needs to be well defined.

Clinical Competence↗

A phase II study on the safety and efficacy of 5-fluorouracil, epirubicin, cyclophosphamide (FEC) followed by paclitaxel in the adjuvant treatment of breast cancer.

The incorporation of a taxane into an anthracycline-containing regimen in the adjuvant treatment of breast cancer is a promising approach. In this study, we aimed to evaluate the safety and efficacy of four cycles of FEC (fluorouracil 500 mg/m2, epirubicin 70 mg/m2, cyclophosphamide 500 mg/m2, every 3 weeks) followed by four cycles of paclitaxel (175 mg/m2 every 3 weeks) in the adjuvant treatment of node-positive and other high-risk breast cancer patients. A total of 88 female patients were enrolled. Mean age (+/- SD) of the patients was 47 +/- 10 (min: 24; max: 71). The patients were followed for a median of 48 months (min: 20; max: 64). The most common side effects were nausea-vomiting (grade I-II: 91%; grade III: 2%), as well as hematological toxicity (grade I-II: 70%; grade III: 3%). Although all patients experienced some degree of toxicity, it was severe enough to be classified as grade III or IV in only 10 (11%) of the cases. Of note, six (8%) patients had grade I and only one (1%) had grade II cardiotoxicity. No grade III or IV cardiotoxicity was observed. The full eight cycles of study treatment could be administered to 75 patients (85%). Side effects necessitated the reduction of the doses of FEC and paclitaxel in one (1%) and three patients (3%), respectively. Median overall (OS) and disease-free survival (DFS) have not yet been reached. Five-year OS and DFS have been estimated to be 78% and 61%, respectively. We conclude that FEC followed by paclitaxel is a well-tolerated and feasible regimen in the adjuvant treatment of early breast cancer. Its efficacity is comparable with other commonly used regimens and merits evaluation in a phase III study.

Adult↗

Neoadjuvant chemotherapy with cyclophosphamide, mitoxantrone, and 5-fluorouracil in locally advanced breast cancer.

OBJECTIVES: Our primary objective was to determine the response rate; secondary objectives were to assess the toxicity rate, and disease-free and overall survival rates in patients with locally advanced breast cancer (LABC) receiving a cyclophosphamide (500 mg/m2), mitoxantrone (12 mg/m2) and 5-fluorouracil (500 mg/m2) (CMF) chemotherapy regimen. PATIENTS AND METHODS: The data from 74 patients with LABC with neoadjuvant CMF chemotherapy were analyzed retrospectively. Preoperatively, all patients received 3 cycles of CMF on day 1, repeated every 21 days. In 3 (4.1%) patients, breast-conserving surgery was given and in 71 (95.9%) modified radical mastectomy. All patients received radiotherapy and 3 additional cycles of CMF chemotherapy after surgery. RESULTS: Median age of the patients was 47 years (range: 17-74). 43 patients were premenopausal, whereas 31 were postmenopausal. 54 patients were in stage IIIA, and 20 were in stage IIIB. The overall clinical response rate was 88%; 11 (14.9%) had a complete response, 54 (73%) had a partial response, and 2 (2.8%) had progression. 14 (18.9%) had a pathological complete response. The median follow-up was 62 months. The median disease-free survival was 64.9 months, and the median overall survival was 97.5 months. The 5-year disease-free and overall survival rates were 52% and 79.9%, respectively. Most frequent side-effects were nausea/vomiting, mucositis, alopecia and leukopenia. CONCLUSION: The CMF regimen has a high overall response rate and an acceptable side effect profile in the treatment of locally advanced breast cancer. Further studies are needed to evaluate its effectiveness in breast-conserving strategies.

Adolescent↗

The evaluation of first aid and basic life support training for the first year university students.

In Turkey, the first aiders are few in quantity and yet they are required in many settings, such as earthquakes. It was thought that training first year university students in first aid and basic life support (FA-BLS) techniques would serve to increase the number of first aiders. It was also thought that another problem, the lack of first aid trainers, might be addressed by training medical students to perform this function. A project aimed at training first year university students in FA-BLS was conducted at Hacettepe University. In the first phase, medical student first aid trainers (MeSFAT) were trained in FA-BLS training techniques by academic trainers and in the second phase, first year university students were trained in FA-BLS techniques by these peer trainers under the academic trainers' supervision. The purpose of this study was to assess the participants' evaluation of this project and to propose a new program to increase the number of first aiders in the country. In total, 31 medical students were certified as MeSFATs and 12 of these trained 40 first year university students in FA-BLS. Various questionnaires were applied to the participants to determine their evaluation of the training program. Most of the participants and the authors considered the program to be successful and effective. This method may be used to increase the number of first aid trainers and first aiders in the community.

Adolescent↗

Clinicopathologic and radiopharmacokinetic factors affecting gamma probe-guided parathyroidectomy.

HYPOTHESIS: The kinetics of technetium Tc 99m sestamibi (MIBI) in primary hyperparathyroidism are variable and affected by the cellular size of the abnormal glands, the parathyroid hormone levels, and the functional expression of P-glycoprotein (Pgp). The success of gamma probe-guided parathyroidectomy is closely related to the parathyroid-to-thyroid activity ratio at the time of surgery. Preoperative determination of maximum uptake ratio may improve the surgical outcome. DESIGN: Thirty-one patients with primary hyperparathyroidism attributed to a solitary parathyroid adenoma (27 patients) or multiglandular hyperplasia (4 patients) underwent dynamic MIBI imaging preoperatively. Maximum MIBI activity and activity elimination half-life in the abnormal parathyroid glands and thyroid glands were measured, and the maximum uptake ratio was calculated. After a second MIBI injection on the day of surgery, all patients underwent gamma probe-guided parathyroidectomy and cervical exploration. Timing of surgery after MIBI injection was individualized according to the optimal time to surgery (time to maximum uptake ratio), which was determined by preoperative scintigraphy. During surgery, the gamma probe was used to measure ex vivo counts of excised lesions and adjacent postexcision normal tissue (background). Image characteristics, MIBI kinetics, and gamma probe findings were correlated with gland volume, oxyphil cell content, Pgp expression, and serum parathyroid hormone levels. RESULTS: Probe localization of abnormal glands at maximum uptake ratio was successful in all patients. The volume of the parathyroid lesion ranged from 0.03 to 9.8 mL (median, 0.7 mL). Parathyroid maximum MIBI activity correlated with the volume of the gland (r = 0.54, P = .002) and serum parathyroid hormone level (r = 0.58, P = .001). No correlation between maximum MIBI activity and oxyphil cell content or Pgp expression could be demonstrated. Elimination half-life of MIBI from parathyroid inversely correlated with Pgp (r = -0.36, P = .05). The ex vivo lesion-background count ratio positively correlated with volume of the gland (r = 0.66, P = .001) and parathyroid hormone level (r = 0.48, P = .006). Ex vivo lesion counts and Pgp expression were negatively correlated (r = -0.37, P = .04). CONCLUSIONS: A strong relationship between volume of the parathyroid gland, serum parathyroid hormone levels, and MIBI uptake exists in primary hyperparathyroidism. Gamma probe-guided localization of abnormal gland(s) can be more successful if surgery is undertaken at maximum uptake ratio. High Pgp expression increases MIBI parathyroid clearance rate, decreases gamma probe counts, and may significantly alter the optimal time to surgery.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Cystic hydatid disease: current trends in diagnosis and management.

Cystic echinococcosis is endemic in certain parts of the world. The growth of the cyst is often slow, and the liver and lungs are the most frequently involved organs. Diagnosis is based on clinical signs and symptoms and epidemiological data, while ultrasonography is important for the classification of hydatid cysts. Although certain types of hydatid cysts are successfully treated by percutaneous aspiration, injection, and reaspiration, surgery remains the treatment of choice. We reviewed the current trends in the diagnosis and management of cystic echinococcosis, with special emphasis on hepatic and pulmonary involvement.

Animals↗

Assessment of knowledge and skills in primary health care services: senior medical students' self-evaluation.

BACKGROUND: The responsibility of medical schools is to educate physicians who are able to provide integrated health care services including curative and preventive components to individuals and the community. They should acquire the necessary knowledge and skills for management of health services with a scientific background and necessary skills to conduct research and be able to make plans to improve the health level of the community. PURPOSE: This study aims to examine last-year students in Hacettepe University Medical School and how they assess their knowledge and skills in providing primary health care services. METHODS: The study includes all last-year students in the 2000 to 2001 academic years; 80.4% of the students (n = 313) participated in the survey. The last-year students assessed their own knowledge and skills by using a 5-point scale ranging from 1 (none) to 5 (very good). RESULTS: According to the scoring of the scale, it is found that their level of knowledge is 2.82, and the level of skill is 2.44 for all primary health care services, between low (2) and intermediate (3). A small sample of available students was interviewed regarding these low ratings of their knowledge and skills. CONCLUSIONS: The findings of the study clearly indicate that the curriculum of the medical school does not satisfy the expectations that the newly graduated physicians have the sufficient knowledge and skills necessary for the primary health care services; the graduates have to work just after their graduation from medical school in the health system of Turkey.

Adult↗

A faculty development program evaluation: from needs assessment to long-term effects, of the teaching skills improvement program.

BACKGROUND: We evaluated whether the faculty development program, the Teaching Skills Improvement Program, met medical educators' needs at Hacettepe University Faculty of Medicine, Turkey. In a 1997 needs assessment survey, large proportions of 178 medical educators assessed their knowledge of educational issues and teaching skills as good or excellent. Nonetheless, 86% of the respondents stated they would like to participate in a future training program focused on the content indicated in the survey. DESCRIPTION AND EVALUATION: In 1998, 83 faculty members took part in the program and expressed a high degree of satisfaction with its content and organization, as well as the course trainers' teaching. Most of the participants got high scores on a test of knowledge related to the course content and performed proficiently in a microteaching session. CONCLUSION: Six months to a year later, large proportions of the participants reported using many of the training techniques in their teaching program.

Clinical Competence↗

Diagnostic and therapeutic ERCP in hepatic hydatid disease.

BACKGROUND: This retrospective study evaluated the use of diagnostic and therapeutic ERCP in pre- and postoperative patients with hepatic hydatid disease. METHODS: For 8 years, ERCP was performed in 39 patients with hepatic echinococcal disease. Indications in the preoperative group of patients (n = 19) included a cholestatic enzyme profile in all cases; jaundice or acute cholangitis also was present in, respectively, 14 and 7 cases. In the postoperative group (n = 20), indications for ERCP included persistent external biliary fistula after surgery in 10 patients, jaundice in 8, acute cholangitis in 7, and right upper quadrant pain in 2 patients. RESULTS: ERCP findings in the preoperative group included cystobiliary fistula (9 patients), external compression of the hepatic biliary system (5), hydatid vesicles and/or membranes within the biliary tract (3), intrahepatic duct stricture (1), and a normal cholangiogram (4). The most common ERCP finding in the postoperative group was external biliary fistula (10 patients); other findings consisted of hydatid cyst material within the bile duct (4), bile duct stenosis (2), cystobiliary fistula and hydatid cyst material in the bile duct (1), cystobiliary fistula (1), hydatid membranes in the gallbladder (1), extrinsic compression to bile ducts (1), and a normal cholangiogram (1). In the preoperative group, endoscopic sphincterotomy was performed in 11 patients, with balloon catheter extraction in 2; complete resolution of findings was achieved in 10 cases. In the postoperative group, sphincterotomy (with balloon or basket extraction as needed) was performed in 19 patients, stents were placed in 2 patients, 1 patient underwent balloon dilatation, and 1 had nasobiliary drainage; there was complete resolution of the findings in 14 of the 20 patients. CONCLUSIONS: ERCP and related therapeutic maneuvers are safe and valuable in the pre- and postoperative management of patients with hepatic hydatid disease.

Adult↗

Optimization of the gamma probe-guided parathyroidectomy.

The objective of this study was to determine the patient-specific optimal time to surgery preoperatively to improve operative success in gamma probe-guided parathyroid localization. Fifteen patients with hyperparathyroidism underwent a double-phase Tc99m-MIBI (15-20 mCi) parathyroid scintigraphy to study the Tc99m-MIBI clearance kinetics from parathyroid and thyroid glands and to determine the time point at which the optimal target-to-background ratio was achieved. Optimal time to surgery was determined on the basis of the time at which the target-to-background ratio was maximal. On the day of surgery the patients received the same dose of Tc99m-MIBI and were taken to the operating room at the time of optimal target-to-background ratio. A four-gland exploration was performed with identification and excision of hot lesions using a gamma probe. Ex vivo lesion-to-background ratios were determined. Histopathologic confirmation of a successful parathyroidectomy was obtained intraoperatively by frozen section. The total operative time and the time to localize and excise the parathyroid glands were recorded. The mean surgery time was compared with that of previous parathyroidectomies performed by the same surgical team without use of preoperative scintigraphy and intraoperative gamma probe. Scintigraphy correctly localized parathyroid pathology in 12 of 15 (80%) patients. Intraoperative gamma probe was successful in 15 of 15 (100%). The optimal time to surgery was found to be different for each patient, and the mean time was calculated as 136 +/- 43 minutes. Mean surgery time for the excision of parathyroid gland was 91 +/- 46 minutes, which was significantly shorter than previous four-gland exploration without use of scintigraphy and gamma probe (160 +/- 61 minutes; t = 3.021, P = 0.007). The mean ex vivo lesion-to-background gamma probe count ratio of abnormal parathyroid glands (77.35) was found to be significantly higher than that of all other lesions with abnormal Tc99m-MIBI uptake (5.05) (U = 10.5, P < 0.0001). Optimal target-to-background ratio is essential for the success of gamma probe-guided parathyroidectomy. This ratio was highly variable among the patients in this study. Individualization of the best surgical exploration time after Tc99m-MIBI injection will improve the surgical success of this operation.

Adult↗