Increased Level of Serum Hepcidin in Female Adolescent Athletes.

OBJECTIVE: To determine the serum hepcidin concentration and standard hematological parameters in a group of female adolescent athletes, compared with a group of nonathlete females. DESIGN: A case-control study. SETTING: A senior high school for athletes in Gothenburg, Sweden. PARTICIPANTS: All female athletes (70), at the school were offered to take part. Fifty-six athletes accepted. From a random sample of age-matched nonathletes, 71 students were recruited to the control group. MAIN OUTCOME MEASURES: Iron deficiency (ID) was determined by levels of serum iron, total iron-binding capacity, transferrin saturation (TS), and ferritin. Serum hepcidin was determined by a mass spectrometry method. All samples were taken at least 12 hours after training. RESULTS: The main result was the finding of a significantly elevated serum hepcidin level in the athlete group, 4.7 nmol/L compared with 3.3 nmol/L (P < 0.001) in the nonathlete group. In the athlete group, the serum iron concentration was significantly lower, 14.0 µmol/L compared with 17.6 µmol/L (P = 0.003) in the nonathlete group. No difference was found regarding TS, total iron binding capacity, and ferritin. There was no difference in the occurrence of ID or iron deficiency anaemia (IDA). CONCLUSIONS: These findings show an increase in serum hepcidin in a large group of female athletes. The elevated hepcidin levels may affect the iron balance of the athletes, adding to the traditional explanation of dietary intake/iron loss balance.

Iron deficiency in adolescent female athletes - is iron status affected by regular sporting activity?

OBJECTIVE: To determine the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) among a group of female athletes and compare with an age-matched group of female nonathletes. To study lifestyle factors that could play a role in the development of ID and IDA and compare these factors between the groups. DESIGN: A controlled clinical trial. SETTING: A senior high school for athletes in Gothenburg, Sweden. PARTICIPANTS: All female athletes at a senior high school for top-level athletes were offered to take part. Fifty-seven female athletes accepted to participate in the study. The control group consisted of a random sample of 130 age-matched nonathlete students; 92 accepted to participate in the study. INTERVENTION: Intervention was not an actual part of this study but those with ID and IDA were treated with iron by the regular school doctor. MAIN OUTCOME MEASURES: Iron deficiency anemia and ID were determined by levels of hemoglobin, serum iron, total iron-binding capacity, transferrin saturation, and serum ferritin. RESULTS: The main result of the study is the finding that ID and IDA are common among young adolescent female athletes and that there was no difference between female athletes and nonathletes. In the athlete group, 30 of 57 individuals (52%) had ID compared with 43 of 92 individuals (48%) in the nonathlete group (P > 0.3). Comparisons of the 2 groups showed no significant difference in hemoglobin (P > 0.30). In total, we found that 5 of 57 athletes (8.6%) had IDA compared with 3 of 92 nonathletes (3.3%), the difference being not statistically significant (P = 0.24). CONCLUSIONS: The main finding of this study is that ID and IDA are common among female adolescents but not more common among athletes than nonathletes. The results are despite factors that should favor a better iron status in the athlete group, such as better iron intake and less menstrual bleeding. Other factors that might have an impact on iron balance, must therefore be considered.

Melphalan 100 mg/m2 with stem cell support as first relapse treatment is safe and effective for myeloma patients with long remission after autologous stem cell transplantation.

INTRODUCTION: Today, a number of therapeutic options are available as the patient with myeloma relapses from initial treatment with high-dose melphalan and autologous stem cell transplantation (ASCT). For patients who experience a durable response to primary ASCT, retreatment with high-dose melphalan is recommended by many current guidelines. Yet, toxicity is an important aspect in the choice of relapse treatment, and a second ASCT in this setting could be associated with enhanced toxicity. As the goal for the treatment for relapsed myeloma should be disease control while maintaining quality of life, lower doses of melphalan might be preferable. METHODS AND OBJECTIVES: In this retrospective study, we account for the outcome of 66 patients with myeloma in first systemic relapse after ASCT, who were treated with intermediate-dose melphalan, 100 mg/m2, and stem cell support (MEL 100). The aim was to evaluate this treatment in relation to prior response duration after initial ASCT and with respect to response rate, toxicity and survival. RESULTS: The overall response rate was 62%. There was limited, mostly haematological, toxicity, and no treatment-related mortality was observed. The median progression-free survival (PFS) was 8.5 months, and the median overall survival was 24 months. Patients with time to progression of 34 months or more (n=17; ≥75th percentile) after initial ASCT had a median PFS of 12.5 months after MEL 100. CONCLUSION: For patients with a long-lasting response after ASCT, MEL 100 could be a therapeutic option with low toxicity and with efficacy comparable to newer immunomodulatory drugs.

"I couldn't do this with opposition from my colleagues": a qualitative study of physicians' experiences as clinical tutors.

BACKGROUND: Clinical contact in the early curriculum and workplace learning with active tutorship are important parts of modern medical education. In a previously published study, we found that medical students' tutors experienced a heavier workload, less reasonable demands and less encouragement, than students. The aim of this interview study was to further illuminate physicians' experiences as clinical tutors. METHODS: Twelve tutors in the Early Professional Contact course were interviewed. In the explorative interviews, they were asked to reflect upon their experiences of working as tutors in this course. Systematic text condensation was used as the analysis method. RESULTS: In the analysis, five main themes of physicians' experiences as clinical tutors in the medical education emerged: (a) Pleasure and stimulation. Informants appreciated tutorship and meeting both students and fellow tutors, (b) Disappointment and stagnation. Occasionally, tutors were frustrated and expressed negative feelings, (c) Demands and duty. Informants articulated an ambition to give students their best; a desire to provide better medical education but also a duty to meet demands of the course management, (d) Impact of workplace relations. Tutoring was made easier when the clinic's management provided active support and colleagues accepted students at the clinic, and (e) Multitasking difficulties. Combining several duties with those of a tutorship was often reported as difficult. CONCLUSIONS: It is important that tutors' tasks are given adequate time, support and preparation. Accordingly, it appears highly important to avoid multitasking and too heavy a workload among tutors in order to facilitate tutoring. A crucial factor is acceptance and active organizational support from the clinic's management. This implies that tutoring by workplace learning in medical education should play an integrated and accepted role in the healthcare system.

Hepcidin, interleukin-6 and hematological iron markers in males before and after heart surgery.

Anemia of inflammation in patients with acute or chronic acute-phase activation is a common clinical problem. Hepcidin is a peptide shown to be the principal regulator of the absorption and systemic distribution of iron. Main inducers of hepcidin are iron overload, hypoxia and inflammation, where the latter has been linked to hepcidin via increased interleukin-6 (IL-6). This article addresses the impact and time course of postoperative acute-phase reaction in humans following heart surgery on prohepcidin, hepcidin, hematological markers and IL-6 concentrations. Serum concentrations of prohepcidin, hepcidin, IL-6 and hematological iron parameters were studied in five male patients without infection before and after heart surgery. This study, which is the first to report the impact on serum hepcidin and serum prohepcidin concentrations in patients following surgery, clearly demonstrates the induction of hypoferremia due to the postoperative acute-phase reaction. Significant changes were seen for serum iron concentration, transferrin saturation, total iron binding capacity and hemoglobin concentration. A significant increase in ferritin concentration was seen 96-144 h postoperatively. Additionally, there were significant alterations in both serum hepcidin after 96-144 h and serum prohepcidin after 48 h compared with preoperative values. Serum prohepcidin decreased, whereas serum hepcidin increased. In conclusion, changes in serum prohepcidin were followed by an increase in serum hepcidin. This speaks in favor of a chain of action where proteolytic trimming of serum prohepcidin results in increased serum hepcidin. However, hypoferremia appeared prior to the changes in serum prohepcidin and serum hepcidin.

Medical students' and facilitators' experiences of an Early Professional Contact course: active and motivated students, strained facilitators.

BACKGROUND: Today, medical students are introduced to patient contact, communication skills, and clinical examination in the preclinical years of the curriculum with the purpose of gaining clinical experience. These courses are often evaluated from the student perspective. Reports with an additional emphasis on the facilitator perspective are scarce. According to constructive alignment, an influential concept from research in higher education, the learning climate between students and teachers is also of great importance. In this paper, we approach the learning climate by studying both students' and facilitators' course experiences.In 2001, a new "Early Professional Contact" longitudinal strand through term 1-4, was introduced at the Sahlgrenska Academy, University of Gothenburg, Sweden. General practitioners and hospital specialists were facilitators.The aim of this study was to assess and analyse students' and clinical facilitators' experiences of the Early Professional Contact course and to illuminate facilitators' working conditions. METHODS: Inspired by a Swedish adaptation of the Course Experience Questionnaire, an Early Professional Contact Questionnaire was constructed. In 2003, on the completion of the first longitudinal strand, a student and facilitator version was distributed to 86 students and 21 facilitators. In the analysis, both Chi-square and the Mann-Whitney tests were used. RESULTS: Sixty students (70%) and 15 facilitators (71%) completed the questionnaire. Both students and facilitators were satisfied with the course. Students reported gaining iiration for their future work as doctors along with increased confidence in meeting patients. They also reported increased motivation for biomedical studies. Differences in attitudes between facilitators and students were found. Facilitators experienced a greater workload, less reasonable demands and less support, than students. CONCLUSION: In this project, a new Early Professional Contact course was analysed from both student and facilitator perspectives. The students experienced the course as providing them with a valuable introduction to the physician's professional role in clinical practice. In contrast, course facilitators often experienced a heavy workload and lack of support, despite thorough preparatory education. A possible conflict between the clinical facilitator's task as educator and member of the workplace is suggested. More research is needed on how doctors combine their professional tasks with work as facilitators.

What factors motivate junior doctors to engage as clinical tutors? A qualitative study.

OBJECTIVES: The study aimed to explore and identify factors motivating junior doctors to engage as long-term clinical tutors in undergraduate medical education. METHODS: In this qualitative study, twenty-seven participants were recruited among junior doctors attending preparatory tutor courses at the Sahlgrenska Academy, University of Gothenburg, and the Primary Healthcare system, West Sweden. They were asked to respond to open-ended questions and write a short account of their needs as clinical tutors for medical students. A qualitative content analysis was performed. RESULTS: A main theme emerged: "Let me develop my skills in a supportive workplace, provide feedback and merits, and I will continue tutoring". Participants described suitable personality as fundamental, and the need to develop professional skills, both as clinical tutors and physicians. Tutor education was an important source of knowledge and stimulation. A workplace environment, supporting learning and the tutor's role, was considered important, including having an adequate time frame. A clear and well-prepared assignment was regarded essential. Junior doctors requested feedback and merits in their work as long-term tutors. Clinical tutorship was considered an optional task. CONCLUSIONS: In this exploratory study, motivating factors of junior doctors' engagement as future long-term tutors were identified. It is important to form a process where junior doctors can build up professional competence as clinical tutors and physicians. To ensure a sustainable tutorship in the future, we suggest that universities and healthcare authorities acknowledge and further study these motivating factors.

Percutaneous vertebroplasty at C2: case report of a patient with multiple myeloma and a literature review.

Percutaneous vertebroplasty (PVP) of the axis is a challenging procedure which may be performed by a percutaneous or a transoral approach. There are few reports of PVP at the C2 level. We report a case of unstable C2 fracture treated with the percutaneous approach. The fracture was the first manifestation of multiple myeloma in a previously healthy 47-year-old woman. After local radiotherapy and chemotherapy, the fracture was still unstable and the patient had been continuously wearing a stiff cervical collar for 9 months. Complication-free PVP resulted in pain relief and stabilization and use of the cervical collar could be discontinued. At 18 months follow-up the patient remained free from pain, the fracture was stable and she had returned to work. The purpose of this article is to present the technical facts and to highlight the benefits and potential complications of the procedure. The technical characteristics of the procedure, the indication and results of the present case are discussed together with previously reported cases of PVP treatment at C2.

Successful mobilization of Ph-negative blood stem cells with intensive chemotherapy + G-CSF in patients with chronic myelogenous leukemia in first chronic phase.

The aim of the study was to investigate the feasibility of mobilizing Philadelphia chromosome negative (Ph-) blood stem cells (BSC) with intensive chemotherapy and lenograstim (G-CSF) in patients with CML in first chronic phase (CP1). During 1994-1999 12 centers included 37 patients <56 years. All patients received 6 months' IFN, stopping at median 36 (1-290) days prior to the mobilization chemotherapy. All received one cycle of daunorubicin 50 mg/m2 and 1 hour infusion on days 1-3, and cytarabine (ara-C) 200 mg/m2 24 hours' i.v. infusion on days 1-7 (DA) followed by G-CSF 526 microg s.c. once daily from day 8 after the start of chemotherapy. Leukaphereses were initiated when the number of CD 34+ cells was >5/microl blood. Patients mobilizing poorly could receive a 4-day cycle of chemotherapy with mitoxantrone 12 mg/m2/day and 1 hour i.v infusion, etoposide 100 mg/m2/day and 1 hour i.v. infusion and ara-C 1 g/m2/twice a day with 2 hours' i.v infusion (MEA) or a second DA, followed by G-CSF 526 microg s.c once daily from day 8 after the start of chemotherapy. Twenty-seven patients received one cycle of chemotherapy and G-CSF, whereas 10 were mobilized twice. Twenty-three patients (62%) were successfully (MNC >3.5 x 10(8)/kg, CFU-GM >1.0 x 10(4)/kg, CD34+ cells >2.0 x 10(6)/kg and no Ph+ cells in the apheresis product) [n = 16] or partially successfully (as defined above but 1-34% Ph+ cells in the apheresis product) [n = 7] mobilized. There was no mortality during the mobilization procedure. Twenty-one/23 patients subsequently underwent auto-SCT. The time with PMN <0.5 x 10(9)/l was 10 (range 7-49) and with platelets <20 x 10(9)/l was also 10 (2-173) days. There was no transplant related mortality. The estimated 5-year overall survival after auto-SCT was 68% (95% CI 47 - 90%), with a median follow-up time of 5.2 years.We conclude that in a significant proportion of patients with CML in CP 1, intensive chemotherapy combined with G-CSF mobilizes Ph- BSC sufficient for use in auto-SCT.

[Experiences from PLUS - program for learning and development in Swedish health care]. / Program för EU-utbildade läkare överbryggar kulturella skillnader.

Experiences from PLUS - program for learning and development in Swedish health care In Sweden, more than half of newly registered physicians have been trained outside of the country. Thus, they are not familiar with Swedish culture and the Swedish healthcare system. To support their introduction to a professional carrier in Sweden, in line with the WHO ethical code for recruitment of health personnel, the health care region of Western Sweden established PLUS - program for learning and development in Swedish Health care. A pilot program has now been completed. The physicians had a good biomedical background, but deficiencies in practical skills, cultural insights and knowledge about Swedish health care.  PLUS was based on principles for adult learning with considerable time for reflection and supervision in a group with experienced colleagues. The program was evaluated by an external evaluator, who concluded that the participants felt more secure in their professional role, more familiar with Swedish Health care and better integrated into their health care team. It was concluded that this should lead to improved patient security and better working environment for the physician as well as his/her coworkers.

[Early professional contact supports professional development of medical students. EPC--a new course in medical education in Gothenburg]. / Tidig yrkeskontakt stärker studenternas professionella utveckling. TYK--en ny kurs i läkarutbildningen i Göteborg.

Early professional contact (EPC) is a new course for medical students during the first two years of the medical curriculum in the Sahlgrenska Academy at Göteborg University. Small groups with four students and one tutor meet one day every month. The students participate in the clinical work together with the physician and his/her staff and practise communication with and examination of patients. In this article we describe the structure, the content, the basic knowledge and values of the course and the learning methods. We also discuss the results from a Course Experience Questionnaire and two focus groups. The students got insights into medical profession and health care and inspiration for future medical profession and confidence with patients. The physicians as tutors in clinical practice have an important role in supporting the medical students to build up their professional confidence by seeing, listening to and acknowledging them. EPC in the biomedical curriculum can help students balance and synthesize different knowledge, skills and attitudes.

Comparison of busulphan, hydroxyurea and allogeneic bone marrow transplantation (BMT) in chronic myeloid leukaemia: BMT prolongs survival.

INTRODUCTION: Whether busulphan-treated patients develop blastic transformation earlier than hydroxyurea treated has been a controversial issue. In a randomised prospective study, we examined the busulphan versus hydroxyurea influence on time to blast crisis and on survival. When we opened our study in 1984, the clinical benefit of allogeneic bone marrow transplantation (BMT) was not well known; to follow up the long-time outcome of this treatment was therefore of great interest. MATERIALS AND METHODS: Previously untreated CML patients were randomly started on either hydroxyurea (30 mg/kg/day) or busulphan (0.1 mg/kg/day). The end points of the study were overall survival and time to blast crisis. A total of 26 patients subsequently underwent BMT. RESULTS: A total of 179 patients were randomised, 90 of hydroxyurea, and 89 to busulphan treatment. There was no significant difference in survival between hydroxyurea- and busulphan-treated patients (P = 0.46); median survival was 3.5 and 3.2 years, respectively. In all, 85 of the patients were subsequently diagnosed with blast crisis, 41 in the busulphan and 44 in the hydroxyurea group. There was no significant difference between the two groups (P = 0.91). The 26 patients who were allotransplanted survived significantly longer than those who were not transplanted (P = 0.0001). The 5-year-survival rates were 50 and 22% and the 10-year-survival rates were 46 and 2%, respectively. The median survival was 4.7 years for the transplanted and 3.3 years for the nontransplanted patients. CONCLUSION: We did not find any difference between hydroxyurea and busulphan treatment, either in overall survival or in blast crisis-free survival; transplanted patients survived significantly longer than nontransplanted patients.

Several chromosomes involved in translocations with chromosome 5 shown with fluorescence in situ hybridization in patients with malignant myeloid disorders.

In many patients with myelodysplastic syndromes or acute myeloid leukemia, complex chromosome aberrations can be seen, among which aberrations of chromosome 5 constitute a substantial part. With conventional cytogenetic technique, these aberrations are often identified as deletions or monosomy 5. We analyzed nine patients who, under conventional cytogenetic analysis, showed deletion or monosomy 5. We used fluorescence in situ hybridization with whole-chromosome painting probes to identify the counterpart chromosome and locus-specific identifiers for 5q31 and 5q33 approximately q34. A deletion of 5q was found concomitant with unbalanced translocations. Our results and cases from the literature showed that material from chromosome 5 could be translocated to almost all chromosomes. All patients but one had short survival; this one patient had a preserved 5q31 and 5q33 approximately q34 but a deletion of the q-arm more centromeric than these bands. In eight of the nine patients, further 14 translocations were revealed, not involving chromosome 5.

Is monosomy 5 an uncommon aberration? Fluorescence in situ hybridization reveals translocations and deletions in myelodysplastic syndromes or acute myelocytic leukemia.

Acquired loss of material from chromosome 5 in bone marrow cells is common in myelodysplastic syndromes (MDS) and acute myelocytic leukemia (AML). In this study, we have applied fluorescence in situ hybridization (FISH) analyses with probes for the three regions 5p15.2, 5q31, 5q33-q34, and whole chromosome 5 painting probes (WCP 5) to investigate what further information could be gained regarding the cytogenetic abnormalities of chromosome 5 in 35 patients with MDS or AML. With FISH, a del(5q) was found in all patients except for two. Translocations of material from chromosome 5 were found in 10 patients. Among 16 patients with clones of monosomy 5 seen by cytogenetics, 14 had deletions or translocations. Different breakpoints on chromosome 5 were observed. In conclusion, the extended FISH analyses yielded additional information about chromosome 5 abnormalities in 60% of the patients. Of interest is the finding of a high proportion of translocations and that monosomy 5 occurs less often than is generally believed.

Secretion rate from minor salivary glands in patients with malignant haematological diseases receiving chemotherapy--a pilot study.

The aim of this pilot study was to investigate the secretion rate from minor salivary glands in 16 patients (mean age 62 years) with myeloma, lymphoma or other malignant haematological diseases receiving chemotherapy (study group). An age- and sex-matched control group (n = 16) was recruited. The secretion rate from the minor salivary glands on the inside of the lower lip, measured using the Periotron method, was in mean 2.8 microliters/cm2/min in the study group compared with 4.5 microliters/cm2/min in the control group (p < 0.01). No difference was found in the secretion rate of paraffin-stimulated whole saliva. There were more individuals who experienced dry mouth in the study group (n = 7) than in the control group (n = 2). The conclusion from this pilot study is that the secretion rate from the minor salivary glands might be reduced in cancer patients treated with chemotherapy.

Helicobacter pylori antibodies and iron deficiency in female adolescents.

OBJECTIVE: Iron deficiency (ID) is a common clinical problem worldwide, affecting primarily females. Helicobacter pylori (HP) infection has been shown to be associated with ID. The objective of this study was to define the prevalence of HP antibodies in female adolescents, and to find out if there was a correlation between HP infection and ID. The secondary aim was to study if regularly performed sporting activity, have any association to HP infection, in itself. DESIGN: A controlled clinical trial. SETTING: A senior high school in Gothenburg, Sweden. SUBJECTS: All female athletes at a senior high school for top-level athletes were offered to take part, and 56 athletes took part in the study. The control group consisted of a random sample of age-matched non-athlete students of which 71 entered the study. MAIN OUTCOME MEASURES: Iron deficiency (ID) and iron deficiency anaemia (IDA) were defined by the use of levels of haemoglobin, serum iron, total iron-binding capacity, transferrin saturation, and serum ferritin, as previously described. HP IgG-antibodies were detected by ELISA. RESULTS: 18 of 127 (14%) adolescent females had antibodies against HP. Only 3% had IDA, while 50% had ID. In total, 66% of the HP positive females had ID compared to 48% of the negative females (p = 0.203). No correlation between sporting activity and HP infection was found. Regarding ethnicity, 11/28 of subjects from medium-high risk areas were HP-positive, compared to 7/99 coming from low-risk areas (p<0.001). CONCLUSION: The main finding of this study is that the prevalence of HP IgG antibodies was 14% in adolescent females. We could not find any difference regarding frequency of ID and IDA, between HP positive and negative individuals. Ethnicity is of great importance for the risk of HP infection, while sporting activity itself seems to have no association to HP-infection.

Therapy-related patterns of cytogenetic abnormalities in acute myeloid leukemia and myelodysplastic syndrome post polycythemia vera: single center experience and review of literature.

A minor fraction of patients with polycythemia vera (PV) develop a terminal acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Analysis of the cytogenetic abnormalities during AML or MDS may help in understanding if this development is part of the natural course of the disease or induced by myelosuppressive therapy. Thirty-six cases with AML or MDS post PV, collected in a single Swedish institution during a 33-year period, are described with special regard to time to development of AML or MDS, therapy given during active PV, and cytogenetic findings during AML or MDS. A further 118 cases of AML or MDS post PV, in whom type of therapy during active PV and cytogenetic findings during AML or MDS were reported, were collected from the literature. AML or MDS developed in our own series after 1-30 years with a fairly constant rate (two cases per year). The most frequent cytogenetic abnormalities were +1q, -5, 5q-, -7, 7q-, +8, +9, 11q-, 13q-, and 20q-. When patients in the total material (n = 154) were divided with regard to treatment during active PV, marked differences were observed. The highest frequency of abnormalities was found in patients given multiple lines of therapy (n = 61), dominating features being -5/5q- in 28 patients (46%), -7/7q- in 19 patients (31%), numerous translocations in 24 patients (39%), and unidentified markers in 22 patients (36%). Half of the patients treated with hydroxyurea alone showed a -5 or 5q- abnormality. In patients treated with phlebotomy alone, +8 and +9 were the most frequent findings. The type of therapy given during active PV influences the type of chromosome abnormalities present during terminal AML or MDS and can also be instrumental in the development of leukemia.

Iron deficiency and anemia: a common problem in female elite soccer players.

The objective of the study was to determine the prevalence of iron deficiency and iron deficiency anemia among elite women soccer players. Hemoglobin, serum iron, serum total iron binding capacity, and ferritin were determined in 28 female soccer players called up for the national team. Of the investigated female soccer players, 57% had iron deficiency and 29% iron deficiency anemia 6 months before the FIFA Women's World Cup. It is concluded that iron deficiency and iron deficiency anemia is common in female soccer players at the top international level. Some might suffer from relative anemia and measurement of hemoglobin alone is not sufficient to reveal relative anemia. Regular monitoring of hemoglobin concentration and iron status is necessary to institute iron supplementation when indicated.